Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 4 Modular Synthesis of Cyclic cis- and trans-,-diamine Derivatives Anna K. Weber, a Robert Fichtler, a Josef Schachtner, b Timo M. Leermann, a Jörg M. Neudörfl a and Axel Jacobi von Wangelin* a,b a Department of Chemistry, University of Cologne, Germany. b Institute of Organic Chemistry, University of Regensburg, Germany. Fax: +49 ()94 94 46; Tel: +49 ()94 94 48 E-mail: axel.jacobi@ur.de Electronic Supporting Information (ESI)
Three-component cyclisation with secondary amines: A ml test tube was charged with the sec-amine (4 mmol), the nitroalkene (4 mmol) in toluene ( ml). The mixture was stirred at C and the aldehyde (4.8 mmol) was slowly added over h. After another 8 h, the solvent and other volatile compounds were removed in oil pump vacuum. The crude product was purified by SiO flash column chromatography (ethyl acetate/cyclohexane) or crystallised from solution (for details see below). -(6-Nitro--phenylcyclohex--enyl)pyrrolidine () C 6 H N O ;.4 g/mol Yield (dr trans,trans / cis,trans) 8% (9/) TLC cyclohexane/ethyl acetate = 4/ R f =.4 m.p..8 C ( MHz, CDCl ) ( MHz, CDCl ) 8 N 4 8 6 NO 9 δ =.-. (m, H, Ph),.9-.9 (m, H, H),.-.8 (H, H), 4.9 (dd,. Hz,. Hz, H, H6), 4.8 (m H, H),.4 (s, H, H),.8 (m, H, H),.68 (m, H, H ),.8-. (m, H, H4),. (s, 4H, H8, H8 ) δ = 9. (C, C9), 8.8 (C, C, C`),. (C, C),.4 (C, C), 4. (C), 9. (C6), 6. (C), 4.8 (C), 4. (C),.9 (C4), 4. (C, C8) FT-IR (ATR): ν [cm-] = 96 (m), 49 (s), 44 (m), 69 (m), 9 (w), (w), (m), 699 (s) LR MS (EI, ev) m/z =, (M + -NO ) HR MS (ESI) calculated [M+H] +.6, measured.6 Dimethyl 6-formyl--methylcyclohexa-,-diene-,-dicarboxylate C H 4 O 8. g/mol Yield 6% TLC cyclohexane/ethyl acetate = 6/ O 4 9 O 6 O Me O O 8 R f =.
δ = 9. (s, H, H),. (dd, J = 8. Hz,. Hz, H, H4),. ( MHz, CDCl ) 6.8 (m, H, H),.8 (s, H, H8),.4.6 (m, H, H),.8 (dt, J = 9.6 Hz,. Hz, H, H),. (s, H, Me) δ = 9. (C),. (C), 6.8 (C9), 44. (C6), 9.4 (C4), ( MHz, CDCl ). (C), 9. (C), 6. (C, C8, C), 4. (C), 4.8 (C),. (Me) FT-IR (ATR): ν [cm-] = 9 (w), (s), 68 (s), 6 (m), 44 (w), 4 (m), (s), 4 (s), 4 (m), (s), 69 (s), 69 (s), 9 (m), 89 (m), (m), (m) LR MS (EI, ev) m/z = 9, (M-Me), 9, 64,,, 9 -(-(,-Dimethoxyphenyl)-6-nitrocyclohex--enyl)pyrrolidine () C 8 H 4 N O 4,.9 g/mol Yield (dr trans,trans / cis,trans) 69% (/) TLC cyclohexane/ethyl acetate = 4/ ( MHz, CDCl ) ( MHz, CDCl ) FT-IR R f =.46 8 N 4 6 MeO 8 NO 9 OMe δ = 6.9-.6 (m, H, Ph),.88-.94 (m, H, H),.4-.8 (m, H, H),.4-. (H, H6), 4.-4.8 (m, H, H),.86-.9 (m, 4H, OMe, H),.8 (s, H, OMe),.8-.8 (m, H, H),.6-. (m, H, H),.-.4 (m, H, H4),.-. (m, 4H, H8) δ =.9 (C, Ph), 9. (C), 4.6 (Ph), 4. (C),. (Ph), 6. (Ph), 89. (C6), 6.4 (C), 6. (OMe),.6 (OMe), 4.8 (C, C ),. (C4), 4. (C8, C8 ) (ATR): ν [cm - ] 964 (m), 86 (m), 688 (w), 84 (m), (s) (NO ), 4 (s), (m), 64 (s), (w), 8 (s), 4 (s), 86 (s), 4 (s) LR MS (EI, ev) m/z = (M + ), 86 (M-NO ), (-OMe), 6,, 69, 48, 4,
-(-(Benzene-,-dioxol-6-yl)-6-nitrocyclohex--enyl)pyrrolidine () C H N O 4, 6. g/mol Yield (dr trans,trans / 9% (4/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =.8 4 N 6 NO 4 8 9 δ = 6.6-6.4 (m, H, H8, H, H),.9 (sbr, H, H, H), ( MHz, CDCl ).6-.8 (m, H, H), 4.-4.68 (m, H, H6), 4.-4. (m, H, H),.9-.4 (m, H, H),.6-.86 (m, 4H, H4),.-. (m, H, H4),.-.6 (m, 4H, H) δ = 46.9 (C),. (C),. (C6), 4.9 ( C),. (C),. ( MHz, CDCl ) (C-4) FT-IR (ATR): ν [cm - ] = 9 (m), 8 (w), 68 (w), (s), (m), 486 (m), 44 (m), 69 (m), 4 (s), (m), (m), (m), 6 (s), 9 (m), 86 (w), 89 (m), 6 (m) O O -(-(,6-Dichlorophenyl)-6-nitrocyclohex--enyl)pyrrolidine (4) 4 C 6 H 8 Cl N O ; 4. g/mol Yield (dr trans,trans / cis,trans) 66% (/) after storage in wet CDCl TLC cyclohexane/ethyl acetate = 4/ ( MHz, CDCl ) ( MHz, CDCl ) R f =. 8 N 4 8 6 Cl NO Cl 9 δ =.-.9 (m, H, H, H ),. (t, H, H),.9-.9 (m, H, H),.6-.84 (H, H), 4.-4.6 (m, H, H), 4.-4.8 (m, H, H),.89-. (m, H, H4),.-.84 (m, H, H ),.64-. (m, H, H),.-.4 (m, H, H4),.-. (m, 4H, H8) δ =. (C9), 4.9 (C),. (C),.4 (C), 9. (C), 9. (C), 8.4 (C), 4.4 (C), 8.9 (C6), 6. (C), 4.8 (C, C ), 4. (C), 9.8 (C4), 4. (C8, C8 ) FT-IR (ATR): ν [cm-] = 96 (m), 89 (m), (m), 64 (m), 46 (s) (ν NO ), 44 (s), 68 (m), 4 (m), 4 (m), 6 (m) LR MS (EI, ev) m/z = 4, 96 (M-NO ), 8 (-Cl), 4 (-Cl), 86,, 4,
-(-Methyl-6-nitro--phenylcyclohex--enyl)pyrrolidine () C H N O, 86. g/mol Yield (dr trans,trans / cis,trans) 94% (8/) TLC cyclohexane/ethyl acetate = 4/ R f =.4 m.p. 6 C ( MHz, CDCl ) ( MHz, CDCl ) Me 8 N 4 8 6 NO δ =.-. (m, H, Ph),.4 (s, H, H), 4.8 (dd, J =. Hz, 9.9 Hz, H, H6), 4.-4.4 (m, H, H),.4-. (m, H, H),.4-.8 (m, H, H),.64-.69 (m, H, H),.6 (s, H, H4),. (s, H, H4),. (s, 4H, H8, H8, Me) δ = 9.4 (C9), 6. (C), 8.9 (C),. (C), 8.6 (C), 9. (C6), 6.4 (C), 4.8 (C), 4.6 (C), 8.9 (C4), 4. (C8),.8 (CMe) FT-IR (ATR): ν [cm-] = 98 (m), 9 (m), (s), 49 (m), 4 (m), 69 (m), 4 (w), 64 (m), 699 (m), 69 (m) LR MS (EI, ev) m/z = 86 M +, 9 (M-NO ), 4 (-Me),,, HR MS (ESI) Calculated [M+H] + 8.4, measured 8. 9 N-(-(,-Dimethoxyphenyl)--methyl-6-nitrocyclohex--enyl)pyrrolidine (6) 6 C 9 H 6 N O 4, 46.4 g/mol Yield (dr trans,trans / cis,trans) 6% (4:) TLC cyclohexane/ethyl acetate = 4/ ( MHz, CDCl ) ( MHz, CDCl ) R f =.4 9 8 N 6 4 MeO NO OMe δ =. (d, H, Ar),. (t, H, Ar),.4 (s, H, H),. (t, J =. Hz, H, H), 4. (d, J = 9. Hz, H, H6),.9-.84 (m H, H4,.88 (s, H, OMe),.84 (s, H, OMe),.8 (d, J = 8. Hz, H, H),.68 (d, J = 6. Hz, H, H),.8.6 (m, H, H8, Me) δ =.8,., 9., 8.,.9, 4., 8.4 (C), 89.6 (C), 6.9 (OMe), 6.98 (OMe),.64 (C6), 4.6 (C, C), 4. (C, C8),.6 (CMe)
FT-IR (ATR): ν [cm-] = 4 (w), 964 (m), 96 (m), 86 (m), (w), 688 (m), 69 (w), 84 (m), (s), (w), 4 (s), 48 (m), 8 (w), 4 (w), 88 (m), 64 (s), 9 (m), 68 (w), (w), 8 (s), 6 (w), 4 (s), 966 (w), 9 (w), 8 (m), 86 (m), 4 (s), 69 (m), 6 (m) LR MS (EI, ev) m/z = 46 M +,, 99, 69, 6,, -(-(Benzo[d][,]dioxol-6-yl)--methyl-6-nitrocyclohex--enyl)pyrrolidine () C 8 H N O 4,.8 g/mol Yield (dr trans,trans / cis,trans) 8% (4/) TLC cyclohexane/ethyl acetate = / R f =.6 m.p. C 9 8 N 6 4 NO O O δ = 6.68 (m, H, Ar),.9 (s, H, H),.4 (s, H, H), 4.6 (dd, ( MHz, CDCl ) J =. Hz, 9.9 Hz, H, H), 4.8 (d, J = 9.8 Hz, H, H6),. (dt, J =.8 Hz, 8.6 Hz, H, H4),.8.69 (m, H, H),..8 (m, H, H),. (d, J = 8. Hz, H, H),.4 (d, J =.4 Hz, H; H8, H9) δ = 4.9 (Ar), 4. (Ar), 6.68 (Ar),. (C),.9 ( MHz, CDCl ) (Ar), 8.4 (C), 8. (Ar),.6 (Ar),. (C), 9.6 (C), 6. (C6), 4.68 (C), 4. (C4), 8.9 (C), 4. (C8),. (CMe) FT-IR (ATR): ν [cm - ] = 96 (m), 9 (m), 8 (w), 68 (w), (s), (m), 486 (m), 44 (m), 69 (m), 4 (s), (m), (m), (m), 6 (s), 9 (m), 86 (w), 89 (m), 6 (m) LR MS (EI, ev) m/z =, 84, 68,, 8,,,, 9 HR MS ESI calculated [M+H] +.6, measured.64
N-(-(-Fluorophenyl)--methyl-6-nitrocyclohex--enyl)pyrrolidine (8) 8 C H FN O, 4.9 g/mol Yield (dr trans,trans / 9 % (8/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =.6 8 9 N 6 4 δ =. (t, H, Ar),. 6.96 (m, H, Ar),.4 (s, H, H), 4.99 ( MHz, CDCl ) (t, J =. Hz, H, H6), 4.6 (d, J = 8. Hz, H H, H),.9 (dt, J =. Hz, 6. Hz, H, H),..6 (m, H, H, H4),.4.8 (m, H, H4),.84.6 (m, H, H8, H9) δ = 6.9 (CF), 6. (C), 9.8 (Ar), 9.6 (Ar), 4. ( MHz, CDCl ) (Ar), 8. (C), 6.4 (Ar),.94 (Ar), 89. (C6), 6.4 (C), 4.6 (C, C),.4 (C4), 4.6 (C, C8),.6 (C9) FT-IR (ATR): ν [cm - ] = 96 (s), 99 (s), 8 (s), 8 (s), 9 (w), 668 (m), 6 (m), 64 (m), 84 (m), (s), (m), 49 (s), 44 (s), 6 (s), 4 (m), 9 (m), 9 (s), 96 (m), 9 (m), (m), 4 (m), 96 (w), 88 (m), 8 (m), 8 (s) LR MS (EI, ev) m/z = 4 M +, 8 (M-NO ), 4, 88,,, 8, 9, 94, HR MS (EI, ev) calculated 4.8, measured 4.9 F NO -(-(,4-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)pyrrolidine (9) 9 C H Cl N O,. g/mol Yield (dr trans,trans / cis,trans) 9% (/) TLC cyclohexane/ethyl acetate = / R f =.9 m.p. C ( MHz, CDCl ) ( MHz, CDCl ) 9 8 N 6 4 Cl NO δ =.9 -,8 (m, H, Ar),. (s, H, H), 4.9 (t, J =. Hz, H, H), 4. - 4.8 (m, H, H6 + H4),.4.9 (m, H, H),.8 (d, J = 6. Hz, H, H, H),..6 (m, H, H),.84.69 (m, H, H8, H9) δ = 6.8 (C, Ar),. (C), 9.84 (Ar), 9. (Ar), 8. (Ar),. (Ar), 8.6 (C), 89. (C), 6. (C6), 4.64 (C, C), 4.6 (C4), 8. (C), 4.4 (C, C8), 4. (C9) Cl
FT-IR (ATR): ν [cm - ] = 96 (m), 9 (m), 84 (m), 668 (w), (s), 44 (s), 4 (w), 68 (m), 6 (w), (w), (w), (w), (m), 46 (w), 9 (w), 86 (m), 8 (s), 64 (w), 44 (m), (m) LR MS (EI, ev) m/z = 4, 8,, 6,,, HR MS (ESI) calculated [M+H] +.94, measured.9 -(-(,6-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)pyrrolidine () C H Cl N O,. g/mol Yield (dr trans,trans / cis,trans) 9% (:) after storage in wet CDCl TLC cyclohexane/ethyl acetate = / R f =. m.p. 8 C 8 9 N 6 4 Cl NO Cl δ =. -.6 (m, H, Ar),. -.8 (m, H, Ar),.9 (dd, J = ( MHz, CDCl ).6 Hz,.9 Hz, H, H6),.6.4 (m, H, H), 4. (td, J =. Hz, 6. Hz, H, H), 4.8 (t, J =. Hz, H, H),.88-.6 (m, H, H4),.6-.66 (m, H, H),.-.64 (m, H, H),.-. (m, H, H4),.8 (s, H, H9),.-.6 (m, 4H, H8) δ = 6. (Ar), 6.9 (Ar), 4. (Ar),. (C),. (Ar), ( MHz, CDCl ) 9. (Ar), 9. (Ar), 8.4 (C), 86.9 (C6), 6. (C), 4. (C, C ), 4. (C),. (C4), 4. (C8, C8 ),.9 (C9) FT-IR (ATR): ν [cm - ] = 96 (m), (s), 4 (s), 6 (m), 8 (w), (m), 8 (w), (w), 8 (w), 6 (s), 9 (w) LR MS (EI, ev) m/z = (M + ), 9,,, 8, 9,,, 94, HR MS (EI, ev) Calculated [M] 4.9, measured 4.9 -(-Methyl-6-nitro--(-nitrophenyl)cyclohex--enyl)pyrrolidine () C H N O 4,.6 g/mol Yield (dr trans,trans / cis,trans) 9% (/) TLC cyclohexane/ethyl acetate = / R f =. m.p. 8 C 9 8 N 6 NO 4 O N
δ =.8 (d, H, Ar),.6.49 (m, H, Ar),.8 (s, H, Ar),. ( MHz, CDCl ) (d, H, Ar),.4 (s, H, H), 4.99 (t, J =. Hz, H, H6), 4.6 (m, H, H + H),.86. (m, H, Ha),.. (m, H, Hb + H4a),. (d, J =. Hz, H, H4b),.8.69 (m, H, H8 + H9) δ = 6.4,.66,.6, 9., 8.4, 8.,.9, ( MHz, CDCl ) 4.8, 8.6, 89.49, 6., 4.8, 4.,.6. FT-IR (ATR): ν [cm-] = 96 (m), 99 (m), 8 (w), 666 (m), 66 (w), (s), 4 (s), 484 (w), 444 (m), (s), 4 (w), 4 (w), 6 (w), 6 (w), (w), 4 (w), 9 (w), 8 (m), 89 (w), 84 (m), 9 (m), 46 (m), (w) LR MS (EI, ev) m/z =, 8, 6,, 96, 8,,, HR MS (ESI) [M+H] + calculated.64, measured.66 -(-(Furan--yl)--methyl-6-nitrocyclohex--enyl)pyrrolidine () C H N O, 6. g/mol Yield (dr trans,trans / 9% (/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =. 8 N 9 4 δ =. (d, H, Ar), 6.8-6.6 (m, H, Ar), 6. (d, H, Ar),.4 ( MHz, CDCl ) (s, H, H), 4.8 (dd, J = 9.9 Hz,. Hz, H, H6), 4.-4.8 (m, H, H),.6-. (m, H, H),.9-. (m, H, H),.6-.6 (m, H, H),.-.48 (m, H, H4),.8-. (m, H, H4),.6 (s, H, H9),.4-. (m, 4H, H8) δ =. (CAr), 4. (CAr), 6. (C), 8. (C),. (CAr), ( MHz, CDCl ). (CAr), 89. (C6), 6. (C), 4.6 (C, C), 8.8 (C),. (C4), 4. (C, C8), 4. (C9) FT-IR (ATR): ν [cm - ] = 964 (m), 94 (m), 84 (w), 8 (w), (s), (w), 48 (w), 68 (m), (m), 4 (w), 4 (w), 4 (m), (w), (m), 9 (w), 88 (m), 8 (m), 6 (s) LR MS (EI, ev) m/z = 6, 9, 4,, 9, 48,, 6 NO O
4-(-(,4-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)morpholine () C H Cl N O,. g/mol Yield (dr trans,trans / cis,trans) NMR: 8% (/); isolated: % (/) TLC cyclohexane/ethyl acetate = / R f =. m.p. -8 C ( MHz, CDCl ) ( MHz, CDCl ) Me 8 O N 4 6 Cl 8 NO δ =.8 (s, H, Ar),.9. (m, H, Ar),. (s, H, H), 4.9 (t, J =.8 Hz, H, H6), 4. (d, J =. Hz, H, H), 4. (d, J = 8. Hz, H, H),..8 (m, 4H, H8, H8 ),.8. (m, H, H ),.6.48 (m, H, H),.9 (d, J = 8. Hz, H, H4),..96 (m, H, H4),. (s, H, Me) δ = 6.48 (C, Ar), 9.9 (Ar),. (C, Ar), 8. (C), 8. (C6), 6.8 (C, C8), 6.86 (C), 48. (C, C), 4. (C),.8 (C4),. (CMe) FT-IR (ATR): ν [cm - ] = 96 (m), 9 (m), 8 (m), 66 (w), 88 (w), (s), 4 (s), 449 (m), (m), 4 (m), 89 (w), (m), (w), 4 (s), 6 (w), 46 (w), (s), 9 (m), 86 (m), 84 (m), 6 (w), (s), 64 (w) LR MS (EI, ev) m/z =,, 88,,,, 8 HR MS (ESI) calculated [M+H] +.9, measured.9 Cl 4-(-(,4-Dichlorophenyl)-4-methyl-6-nitrocyclohex--enyl)morpholine (4) 4 C H Cl N O,.8 g/mol Yield (dr) NMR: %; isolated: % (//) TLC cyclohexane/ethylacetate / R f =. 8 O N 4 8 NO 6 ( MHz, CDCl ) 9 Cl Cl δ =.4 (d, J =.8 Hz, H, Ar),..9 (m, H, Ar),.96 (ddd, J =. Hz, 4.9 Hz,. Hz, H, H),.4 (d, J =. Hz, H, H),. (dd, J =. Hz, 9. Hz, H, H6), 4. (dd, J =.4 Hz,.4 Hz, H, H), 4. (dd, J = 9.6 Hz,.6 Hz, H, H),.4.6 (m, 4H, H8),.8.68 (m, H, H ),.6 (dt, J =.4 Hz, 6. Hz, H, H),.-.4 (m, H, H),.4 (d, J =. Hz, H, H9)
δ =. (Ar), 4.8 (Ar),.8 (Ar),.4 (Ar),. ( MHz, CDCl ) (Ar), 9. (Ar), 6.9 (C),.9 (C), 8. (C6), 6.6 (C, C8), 66. (C), 48.8 (C, C), 4.4 (C),. (C4), 6.4 (C9) FT-IR (ATR): ν [cm-] = 99 (s), 86 (s), 6 (w), (m), 68 (m), 69 (w), 86 (m), (s), (m), 4 (s), (s), (s), 9 (m), 4 (s), 46 (m), (s), 9 (s), 8 (s), 84 (s), (s), 68 (m), 68 (s) LR MS (ESI) m/z = [M+H] +, 4,,,, HR MS (ESI) calculated [M+H] +.9, measured.96 -(-Nitro--phenyl-,,,4-tetrahydrodibenzo[b,d]thiophen-4-yl)pyrrolidine () C H N O S, 8.48 g/mol Yield (dr trans,trans / 8% (/) cis,trans) TLC cyclohexane/ethylacetate = 6/ R f =. m.p. > C (decomp.) 8 N S 4 9 6 4 NO Ph δ =.86.8 (m, H, H, H4),.4-.8 (m, H, H, H, ( MHz, CDCl ) Ph),. (dd, J = 9.9 Hz, 8. Hz, H, H6),. (d, J = 9.4 Hz, H, H ),. (td, J =.6 Hz,.4 Hz, H, H),.4. (m, H, H4),. (dd, J =.9 Hz, 8.6 Hz, H, H),.84 (dd, J = 4. Hz,. Hz, H, H),.9. (m, J =. Hz, 4H, H8) δ = (mixture of two diastereomers) 4., 9.88, 8.6,., ( MHz, CDCl ).8,., 9.9, 9., 8.,.6, 4.68, 4.8, 4.,.,.48,.8,., 9.48, 9.,.4,., 6.6, 6.8, 4., 46.6, 9.8,.99,.6, 9., 4.6 FT-IR (ATR): ν [cm - ] = 8 (w), 9 (m), (s), 46 (w), 46 (w), (w), 6 (w), (m), 4 (m), 6 (m), 4 (w), 84 (w), (s), 8 (s), 699 (s) LR MS (EI, ev) 9, 6, 4,, 8. 6, 9 HR MS (EI, ev) calculated 8.4, measured 8.4
Methyl 6-nitro--(pyrrolidin--yl)-,,,6-tetrahydro-[,'-biphenyl]--carboxylate (6) 6 C 8 H N O 4,.8 g/mol Yield (dr trans,trans / % (6/) cis,trans) TLC cyclohexane/ethylacetate = 6/ R f =.8 m.p. C Me O 9 O 8 N 6 4 8 NO Ph δ =.-.4 (m, H, Ph),. (s, H, H), 4.9 (dd,. Hz,. ( MHz, CDCl ) Hz, H6), 4.-4.4 (m, H, H),.6 (s, H, Me),.9-.48 (m, H, H),.8-.9 (m, H, H, H4),.-.68 (m, H, H, H4),.-.8 (m, 4H, H8, H8 ) δ = 66. (C9), 8. (Ph),.9 (C),. (C), 9. (Ph), ( MHz, CDCl ) 9. (Ph),. (Ph), 9. (C6), 6. (C),. (Me), 48. (C, C ), 4. (C),. (C4), 4. (C8, C8 ) FT-IR (ATR): ν [cm-] = 9 (m), (s), 4 (s), 4 (m), 68 (m), 4 (s), 9 (m), 699 (s) LR MS (EI, ev), 4, 8, 8 HR MS (EI ev) calculated.9, measured.8 -(-Methyl-6-nitro--styrylcyclohex--enyl)pyrrolidine () C 9 H 4 N O,.4 g/mol Yield (dr trans,trans / cis,trans) 9% (/) TLC cyclohexane/ethyl acetate = / ( MHz, CDCl ) R f =. 9 8 N 4 6 NO δ =.. (m, H, Ph), 6.49 (d, J =. Hz, H, H), 6. (dd, J =. Hz, 8.9 Hz, H, H),.44 (s, H, H), 4. (dd, J =.4 Hz,. Hz, H, H6), 4. 4. (m, H, H),. (ddd, J =. Hz,. Hz, 6. Hz, H, H),. (dd, J =.8 Hz, 4. Hz, H, H),.69.9 (m, H, H),.4-.6 (m, H, H4),.4. (m, H, H4),.84.66 (m, H, H8, H9) Ph
δ = 6.46 (Ph), 6. (C),. (C), 8. (C, Ph), ( MHz, CDCl ). (Ph),. (Ph), 6.9 (Ph), 6.4 (C), 8.44 (C), 9.9 (C6), 6.8 (C), 4.6 (C, C), 4. (C), 6.4 (C4), 4. (C, C8),.8 (C9) FT-IR (ATR): ν [cm-] = (w), 96 (m), 869 (m), 66 (m), 9 (w), 49 (s), 49 (m), 44 (m), (m), (m), 4 (w), 9 (w), 68 (w), 8 (w), 964 (m), 99 (m), 4 (s), (s), 69 (s) LR MS (EI, ev) m/z = 6 (M-NO ), 6,,, 9, HR MS (ESI) calculated [M+H] +.9, measured.9 -(-Methyl-6-nitro--phenylcyclohex--enyl)pyrrolidine (8) 8 C H N O, 86.688 g/mol, yellow oil Yield (dr trans,trans / 6% (/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =.8 9 8 N 8 6 4 δ =.8.9 (m, H, Ph),.6 (s, H, H),.9 (dd, J =.8 Hz, ( MHz, CDCl ) 9. Hz, H, H6), 4. (d, J = 9. Hz, H, H),.48. (m, H, H),.94 (dt, J =.8 Hz, 6. Hz, H, H4, H),.4 (dd, J =. Hz,. Hz, H, H),.4.8 (m, H, H4),. (d, J = 6. Hz, H, H8, H9) NO Ph ( MHz, CDCl ) δ = 9. (Ph),. (C), 9.4, 8. (C, Ph),.6 (Ph),. (C, Ph),.4 (C), 9.8 (C6), 6. (C), 4.4 (C, C), 46. (C),.89 (C4), 4.8 (C, C8),.9 (C9) FT-IR (ATR): ν [cm - ] = (m), 96 (s), (w), 69 (m), 68 (m), 6 (s), 46 (s), 448 (s), 4 (s), 6 (s), 9 (s), (m), 6 (m), (m), 9 (w), 96 (s), 844 (m), 8 (m), 6 (s), 699 (s), 648 (m) LR MS (ESI) m/z = 8. [M+H] +, 8,, 44 HR MS (ESI) calculated [M+H] + 8.4, measured 8.
-(,4-Dimethyl-6-nitro--phenylcyclohex--enyl)pyrrolidine (9) 9 C 8 H 4 N O,.9 g/mol, yellow oil 8 8 Yield (dr) 9% (8/6/) TLC cyclohexane/ethyl acetate = / R f =. 9 N 4 6 NO δ =.8.6 (m, H, Ar),.69 (d, J =. Hz, H, H),.4 (dd, J = ( MHz, CDCl ). Hz, 9. Hz, H6), 4.9 (d, J = 8.9 Hz, H, H),.66 (dd, J =.6 Hz,. Hz, H, H),.96 (m, H, H),.8 (m, H, H),.4-.9 (m, H, H4),.9 (dd, J =.6 Hz, 8. Hz, 4H, H8),. (s, H, H9),.8 (d, J =. Hz, H, H) δ = 8.9 (Ph),.4 (C),. (C, Ph), 8. (C, Ph), ( MHz, CDCl ) 8. (C), 84.6 (C6), 6.88 (C), 48. (C), 4.44 (C, C), 6. (C4),. (C, C8),.88 (C9), 6. (C) FT-IR (ATR): ν [cm - ] = (m), 96 (s), 8 (s), 6 (w), 4 (s), 494 (m), 4 (s), (s), 9 (m), (m), 48 (s), 9 (m), 6 (w), (m), (w), 8 (m), (s), (m), 699 (s) LR MS (EI, ev) m/z =,,, 6,, 9 HR MS (EI, ev) calculated.8, measured.84 -(-(4-Methylpent--enyl)-6-nitro--phenylcyclohex--enyl)pyrrolidine () C H N O, 4.48 g/mol Yield (dr trans,trans / 8% (6/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =.6 ' 8 N 6 9 4 δ =.4. (m, H, Ph),.48 (s, H, H),.8 (d, J = 6. Hz, ( MHz, CDCl ) H, H), 4.8 (dd, J =. Hz,. Hz, H, H6), 4.6 (d, J = 8. Hz, H, H),.4 (dt, J =.8 Hz, 8.6 Hz, H, H),.8 (d, J = 6.6 Hz, H, H),..6 (m, H, H),.9 (dd, J =.8 Hz,. Hz, H, H4),.4-. (m, H, H4),. (m, H, H),.84-. (m, H, H9),.6 (s, 4H, H8),. (s, H, H),.64 (s, H, H ) NO Ph
δ = 4. (Ph), 9.4 (C),.9 (C), 8.8 (C, Ph), ( MHz, CDCl ). (Ph),.8 (C, Ph),. (C), 8. (C), 9.6 (C6), 6. (C), 4.6 (C, C), 4.8 (C),.8 (C9), 6. (C), 6.8 (C4),.4 (C), 4. (C, C8),.8 (C ) FT-IR (ATR): ν [cm-] = (w), 96 (m), 9 (m), 669 (w), (s), 494 (w), 44 (w), 4 (m), (w), 4 (w), (w), (w), 8 (w), 84 (w), 6 (m), 698 (s) LR MS (ESI) m/z= [M+H] +, 64,, 69, 6 HR MS (ESI) calculated [M+H] +.8, measured.8 N,N-diallyl--methyl--nitro-,,,6-tetrahydro-[,'-biphenyl]--amine (): N NO C 9 H 4 N O,.4 g/mol Work-up: crude reaction mixture was concentrated to dryness and residue washed with cold pentane/ethyl acetate (/, ml) Yield (dr trans,trans / cis,trans): 8 % (/) Condition: m.p.: beige crystals 8-9 C H-NMR ( MHz, CDCl ) δ =.4 6.9 (m, H),.8.4 (m, H),.4.66 (m, H),.4 (s, H),.9 (d, J =. Hz, H),. (s, H),. (s, H), 4.86 (dd, J =.8, 9.8 Hz, H), 4. 4. (m, H),.4 (ddd, J =.8, 9.4,. Hz, H),..8 (m, H),.8. (m, H),.4 (d, J =. Hz, H),.99 (d, J =. Hz, H),. (d, J =. Hz, H),.4 (s, H). ( MHz, CDCl ) δ =.4,.,.8, 94.9, 66., 64.4, 6.8, 48.8, 4.9, 6.. FT-IR (ATR): ν [cm - ] = 968, 9, 8, 86, 64, 48, 49, 48,,, 6, 6, 9, 86, 996, 96, 9, 86, 86, 6, 698, 6, 6, 96, 4, 46, 48
EI-MS ( ev): [M] + =.84; calculated:.88 (S)--(diphenyl((trimethylsilyl)oxy)methyl)--(--nitro-,,,6-tetrahydro-[,'- biphenyl]--yl)pyrrolidine () C H 4 N O Si, 4.68 g/mol Yield (dr) 46% (by NMR) (/) Ph 8 9 TMSO N Ph 4 6 NO δ =.-. (m, H, Ph),.-.6 (m, H, H),.6-.66 (m, ( MHz, CDCl ) H, H),.9 (t,.6 Hz, H, H6), 4.8 (sbr, H, H), 4.6 (dd,. Hz, 8.9 Hz, H, H),.-.44 (m, H, H),.-.8 (m, H, H),.-.4 (m, H, H-4, H),.6-.9 (m, H, H8),.-. (m, H, H9),.-.4 (m, H, H9) δ = 4.6 (Ph), 4.4 (Ph), 9. (Ph),. (C), 9.9 (Ph), 9.8 ( MHz, CDCl ) (Ph), 8.8 (Ph),. (Ph),. (Ph),.4, (Ph), 6.9 (Ph), 6.4 (Ph),.4, 86.9 (C6), 8. (C), 6.9 (C), 6.8 (C), 4.4 (C),.6 (C4), 9. (C9),.8 (C8),.9 (C, TMS) FT-IR (ATR): ν [cm - ] = 84 (w), (w), 8 (w), 966 (m), 99 (m), 866 (m), 9 (w), 88 (w), (s), 6 (w), 8 (m), 4 (s), (w), 49 (s), 44 (s), (s), 4 (m), 4 (s), 4 (m), 8 (m), 8 (m), (m), 4 (w), 98 (w), 8 (w), 8 (w), 64 (s), 46 (s), 699 (s) (S)--(-(di-(, -bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)--(-methyl-- nitro-,,,6-tetrahydro-[,'-biphenyl]--yl)pyrrolidine () C H 6 F N O Si, 8. g/mol Yield (dr) 86% (8//) TLC cyclohexane/ethyl acetate = / R f =.4 8 9 Ar TMSO N Ar 6 NO 4 ( MHz, CDCl ) δ =.96 (d, 4H, Ar),.9 (s, H, Ar),.. (m, H, Ph),.9 (s, H, H),. (t, J =. Hz, H, H6), 4. (s, H, H), 4. 4. (m, H, H),.9 (dd, J =. Hz, 8.6 Hz, H, H),.8 (dd,
( MHz, CDCl ) J = 6.4 Hz, 8. Hz, H, H4),.4. (m, H, H4, H),..84 (m, H, H8/9),. (s, H, HMe),.69.6 (m, H, H8/9),.4. (m, H, H8/9),.8.6 (m, H, H8/9), -. (s, 9H, TMS) δ = (mixture of two diastereomers) 4.94 (Ar), 4. (Ar), 4. (Ar), 4.8 (Ar),.96 (Ar/Ph), 9. (Ar/Ph), 9.6 (Ar/Ph), 9. (Ar/Ph), 8.8 (Ar/Ph), 8. (Ar/Ph),.9 (Ar/Ph),.4 (Ar/Ph), 6.96 (Ph),.8 (Ph),. (C), 4.69,.94 (C), 8. (C6), 4. (C4), 46.6 (C),.8 (C8), 9. (C), 9.6 (C9),. (CMe),.4 (TMS) (S)--(di-(, -bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)--(-',4'- dichloro--methyl--nitro-,,,6-tetrahydro-[,'-biphenyl]--yl)pyrrolidine (4) 4 C H 4 Cl F N O Si, 88.6 g/mol Yield (dr trans,trans / cis,trans) 8% (9/) TLC cyclohexane/ethyl acetate = / R f =.4 Ar 8 9 TMSO N Ar 4 6 NO Ar =,-(CF ) C 6 H Cl Cl δ =.94 (s, 4H),.8 (s, H),.4 (s, H),.9 (d, H),. (s, H, ( MHz, CDCl ) H),.9 (s, H, H6), 4.6 (s, H, H), 4. (d, J = 8.9 Hz, H, H),.49 (s, H, H),.8 (dd, J = 6. Hz, 8. Hz, H, H4),.4. (m, H, H4,H),.8.8 (m, H),.69 (s, H, Me),,6-, (m, H),-, (m, H), -. (d, J =. Hz, 9H, TMS) δ = (mixture of two diastereomers) 4.4, 4.4,.6, ( MHz, CDCl ).9, 4.98,.9,.4,.,.96,.6,., 9.49, 8.6,.,.,.,.6,.9,.4,.8, 84.8, 8., 6., 6.6, 9.88,.8, 9.,.,.,.4 FT-IR (ATR): ν [cm - ] = 94 (w), 96 (m), 9 (m), 8 (w), 66 (w), 6 (w), 88 (w), 4 (s), 44 (s), 446 (w), 68 (s), (m), 6 (m), (s), (s), (s), 4 (m), 4 (w), 98 (w), 94 (m), 9 (s), 8 (s), 84 (s), 6 (m), (m), 9 (s), 68 (s)
LR MS (EI, ev) m/z = 88, 8, 8, 8 HR MS (ESI) [M+H] + calculated 88.96, measured 88.9 (S)--(-(Benzo[d][,]dioxol--yl)--methyl-6-nitrocyclohex--en--yl)--(di-(, - bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)pyrrolidine () C 8 H 6 F N O Si, 86.69 g/mol Yield (dr trans,trans / % (/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =. 8 9 Ar TMSO N Ar 6 NO 4 6 O Ar =, - (CF ) C 6 H 4 O δ =.9 (d, 4H, Ar),.88 (s, H, Ar), 6. (d, H, H), 6.6-6.6 (6 MHz, CDCl ) (m, H, H, H6),.4 (s, H, H), 4.9 (s, H, H),. (br, H, H), 4. 4. (m, H, H),. (dd, J =. Hz,. Hz, H, H),.6 (dd, J = 6.4 Hz, 8.9 Hz, H, H4),.9 (dd, J = 6. Hz, 9. Hz, H, H4),. (t, J = 8.4 Hz, H, H),.96.8 (m, H, H9/H8),.68 (s, H, HMe),.6 (s, H, H9/H8),.4 (dt, J =.8 Hz, 8. Hz, H, H9/H8),. (dd, J = 9. Hz, 4.9 Hz, H, H9/H8), -.6 (s, 9H, TMS) δ = 4.94 (Ar), 4. (Ar), 4. (Ar), 4.8 (Ar),.9, ( MHz, CDCl ).,., 9. (Ar), 9.4 (Ar),.9 (C), 4.6 (C4),. (C),.9 (C),.9 (C), 8. (C),.4 (C6),.4 (C), 8. (C6), 6.6 (C), 46,4 (C4), 4. (C), 8. (C), 9. (C8),.9 (C9),.46 (CMe),. (TMS) FT-IR (ATR): ν [cm - ] = 96 (w), 8 (w), 8 (w), 64 (w), 4 (s), 48 (s), 4 (w), 69 (s), (m), 6, (s), 69 (s), (s), 86 (s), (m), 4 (m), 9 (m), 9 (s), 8 (m), 84 (s), 86 (m), 64 (m), 48 (m), 9 (s), 68 (s) LR MS (ESI) m/z = 8 [M+H] +, 98, 49,
6 C H 4 F N O 4 Si, 8.8 g/mol Yield (dr trans,trans / 69% (/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =. 8 9 Ar TMSO N Ar 6 NO O 4 Ar =, (CF ) C 6 H δ = 8..99 (m, 6H, Ar),. (s, H), 6.4 (dd, J =. Hz, ( MHz, CDCl ).9 Hz, H), 6. (d, J =. Hz, H),.6 (s, H, H),.9 (s, H, H6), 4.6 (s, H, H), 4.6 (dd, J = 9.,. Hz, H, H),.6 (td, J =.4 Hz,. Hz, H, H),.86 (dd, J = 6. Hz, 8.9 Hz, H, H4),.6.49 (m, H, h4),.4. (m, H, H),.9.9 (m, H H8/H9),.84 (s, H, HMe),.8.6 (m, H, H8/H9),.64.4 (m, H, H8/H9),.4.6 (m, H, H8/H9), -. (s, 9H, TMS) δ =.66, 4.,.4, 9.,.9,.,.8, ( MHz, CDCl ).,., 8.6, 8., 6.4, 6.98, 8., 4.4, 9.6,.4,.49,. (TMS) FT-IR (ATR): ν [cm - ] = 9 (m), 9 (w), 866 (w), 86 (w), 6 (w), 68 (w), 6 (w), (s), 6 (w), 466 (w), 6 (w), 68 (s), (w), (s), (s), (s), 9 (s), (m), 94 (s), 8 (m), 84 (s), (m), (m), 9 (s), 68 (s) LR MS (ESI) m/z = 8 [M+H] +, 98, 4, 9 HR MS (ESI) [M+Na] + calculated 8.988, measured 8.988 (S)--(-(di-(, -bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)--(-(furan-- yl)--methyl-6-nitrocyclohex--en--yl)pyrrolidine (6) (S)--(Di-(, -bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)--(-methyl-,'- dinitro-,,,6-tetrahydro-[,'-biphenyl]--yl)pyrrolidine () C H F N O Si, 8. g/mol Yield (dr 4% (/) trans,trans / cis,trans) TLC cyclohexane/ethylacetate = / R f =. Ar 8 9 TMSO N Ar 4 O N 6 NO Ar =, (CF ) C 6 H
δ = 8..9 (m, 6H, Ar),. (s, H),.4 (t, J =. Hz, H),.9 ( MHz, CDCl ) (s, H, H),. 4.9 (m, H, H6), 4. 4.4 (m, H, H), 4. (s, H, H), 4.6 (d, J = 8. Hz, H),.8 (d, J =. Hz, H, H4),.9 (s, H, H4/H),.6 (s, H, H4/H),.8 (s, H, H8/H9),..86 (m, H, H8/H9),. (s, H, HMe),.6 (d, J =. Hz, H, H8/H9),. (d, J = 6. Hz, H, H8/H9), -.8 (s, 9H, TMS) δ =.4, 4.,.8,.,.96, 9.4, 8.44,.9, ( MHz, CDCl ) 4.99, 4.,.,.9,., 6., 9., 6.9,.,.4,.46 FT-IR (ATR): ν [cm - ] = 969 (w), 6 (w), 4 (m), (m), 448 (w), 69 (m), (w), 6 (s), (s), (s), 4 (w), 9 (s), 8 (m), 86 (m), 84 (s), 84 (w), 6 (w), 46 (w), 9 (s), 68 (s) LR MS (ESI) m/z = 88 [M+H] +, 6 HR MS (ESI) [M+Na] + calculated 88.46, measured 88.48 (S)--(Di-(, -bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)--('-fluoro-- methyl--nitro-,,,6-tetrahydro-[,'-biphenyl]--yl)pyrrolidine (8) 8 C H F N O Si, 8. g/mol Yield (dr 96% (/) trans,trans / cis,trans) TLC cyclohexane/ethyl acetate = / R f =.4 Ar 8 9 TMSO N Ar 4 6 NO F Ar =, (CF ) C 6 H δ =.9 (d, J = 8.8 Hz, 6H),. 6.9 (m, 4H),. (t, J =. Hz, ( MHz, CDCl ) H H6),.6 (s, H, H), 4. (s, H, H), 4.4 (dd, J = 9.,. Hz, H, H),.8 (s, H, H),.8 (dd, J = 6. Hz, 8.9 Hz, H, H4),.49.9 (m, H, H4, H),.9.8 (m, H, H),.69 (s, H, HMe),.8 (s, H, H8/H9),. (d, J =. Hz, H, H8/H9), -.6 (s, 9H, TMS) δ = 69., 4.4, 4.,.8,.44, 9.48, 8.66,., ( MHz, CDCl ) 4.,.44,.8,.4,.8, 6., 6., 84.9, 6., 6., 6.9, 6.4, 9.,.,.4,.4, 4.8,. (TMS)
FT-IR (ATR): ν [cm - ] = 9 (w), 96 (w), 9 (w), 8 (w), 6 (w), 48 (s), 49 (m), 44 (m), 69 (s), 4 (m), 6 (w), 6 (s), (s), (s), 96 (s), 8 (m), 84 (s), 8 (s), 9 (s), 68 (s) LR MS (ESI) m/z = 8 [M+H] +, 6, 8 HR MS (ESI) [M+H] + calculated 8.8, measured 8.89 Methyl (-((S)--(di-(, -bis(trifluoromethyl)phenyl)((trimethylsilyl)oxy)methyl)- pyrrolidin--yl)-6-nitro-,,,6-tetrahydro-[,'-biphenyl]--carboxylate (9) 9 C 8 H 6 F N O Si, 86.69 g/mol Yield (dr trans,trans / 68% (/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =. Ar 8 9 TMSO N Ar MeO C 4 6 NO Ar =, (CF ) C 6 H δ =.9 (d, H, Ar),.88 (s, 4H, Ar),.4.8 (m, H),. (d, ( MHz, CDCl ) H), 6. (s, H, H),. (t, H, H6), 4.89 (s, H, H), 4. (dd, J = 9.4 Hz,. Hz, H, H),. (d, J = 4.8 Hz, H, HMe),. (td, J =.6,. Hz, H),.8 (dt, J =.9 Hz,. Hz, H, H4/H),.6.9 (m, H, H4/H),.8. (m, H, H4/H),.96 (dd, J =.8 Hz,. Hz, H, H8/H9),.69.4 (m, H, H8/H9),.8 (d, J = 8. Hz, H, H8/H9), -. (d, J =. Hz, 9H) δ = 6.66, 44., 4.88, 9.6,.,.6,.4, ( MHz, CDCl )., 9.8, 9., 8.,.8,., 4.9,.,.9,.68, 8.4, 84., 6.68, 6.,.4, 4.,., 6.9,.,.4 FT-IR (ATR): ν [cm - ] = (w), 4 (w), 966 (w), 98 (w), 846 (w), (m), (s), (m), 4 (m), (s), 6 (m), (s), (s), 96 (m), 84 (m), 64 (m), (m), 68 (s) LR MS (ESI) m/z = 8.8 [M+H] +, 89.9, 98.6, 6., 486.,., 4.
N-(-Phenyl--methyl-6-nitrocyclohex--enyl)--diphenyl(pyrrolidin--yl)methanol () C H N O, 468.86 g/mol Yield (dr trans,trans / 8% (4/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =.8 Ph HO Ph 8 9 N 6 4 δ =.69 -.6 (m, H),. -. (m, H),. (t, H),.8.9 ( MHz, CDCl ) (m, 6H),.6 -.4 (m, H), 6.98 (d, H),.9 (s, H, H), 4.44 (s, H, H6), 4.4 4.6 (m, H, H), 4. (s, H),.6 (s, H, H),.. (m, H, H/H4),.99 (dt, J = 4.9 Hz,.6 Hz, H, H4/H),.6 (dd, J =. Hz,. Hz, H, H8/H9/H),.9 (d, J =. Hz, H, H8/H9/H),.9.8 (m, H, H8/H9/H),.8. (m, H, H8/H9/H),. (s, H, HMe),.69.6 (m, H, H8/H9/H) δ =.89, 4.6, 4.89, 6.,.4, 9.,., ( MHz, CDCl ) 4.4,.,.,.4,., 8., 8.6, 6.6, 6.9,.6, 9.,.8,.4 FT-IR (ATR): ν [cm - ] = 4 (w), 84 (w), (w), 8 (w), 966 (m), 99 (m), 866 (m), 9 (w), 88 (w), (s), 6 (w), 9 (m), 44 (s), 8 (w), 49 (s), 44 (s), (s), 4 (m), 6 (s), 4 (m), 8 (m), 8 (m), (m), 4 (w), 98 (w), 8 (w), 8 (w), 64 (s), 46 (s), 69 (s) LR MS (ESI) m/z = 469 [M+H] +, 6, 69 HR MS (ESI) [M+Na] + calculated 49., measured 49.4 NO N-(-(,4-Dichlorophenyl--methyl-6-nitrocyclohex--enyl)--diphenyl(pyrrolidin-- yl)methanol () C H Cl N O,.468 g/mol Yield (dr trans,trans / 8% (6/) cis,trans) TLC cyclohexane/ethyl acetate = / R f =.9 Ph HO Ph 8 9 N 6 4 NO Cl Cl δ =.68 (d, H),. (d, J =. Hz, H),. (t, H),..6 (m, (6 MHz, CDCl ) H),..9 (m, H),.9.8 (m, H),.6 (dd, J =.9 Hz,
( MHz, CDCl ) FT-IR. Hz, H),. (s, H), 4.9 (td, J =. Hz, 6. Hz, H), 4.4 (d, J = 8. Hz, H), 4. 4. (m, H), 4. (s, H),.6 (d, J =. Hz, H),. (s, H),.6.4 (m, H),.. (m, H),.9.8 (m, H),..6 (m, H) δ = (mixture of two diastereomers) 4.8, 46.9,.,.4, 4.9,.8,.8, 8.9, 8.8, 8., 8., 8.6, 8., 6., 6.9,.6,.6,.9,.46,.8, 86.6, 8.6, 6.84, 4., 48.,.6,.6,.4, 6.94, 4.8,.9 (ATR): ν [cm - ] = 48 (w), 9 (w), 8 (m), 46 (s), (s), 468 (m), 44 (s), (m), (m), 4 (s), 6 (w), 6 (w), (m), (s), 6 (m), (w), 886 (w), 866 (m), 8 (m), 9 (m), 4 (s), (s) -(-(Phenyl--methyl-6-nitrocyclohex--enyl)pyrrolidin--yl)methanol () C 8 H 4 N O, 6.948 g/mol Yield (dr) 6% (4/9/) 8 9 N 6 4 OH NO δ =.4 6.96 (m, H), 6. 6.9 (m, H),.4 (s, H), 4.98 (dd, J ( MHz, CDCl ) =.8 Hz, 9.8 Hz, H), 4. 4. (m, H),.44 (ddt, J = 9. Hz,. Hz, 4. Hz, H),..98 (m, H),.8.6 (m, H) δ = (mixture of two diastereomers) 9.,.,.8, 9.6, ( MHz, CDCl ) 8.9, 8.9, 8.6,.8,.,.8,., 9.8, 8.6, 9.96, 9.8, 6.6, 6., 6., 6.4, 6.6, 9.,.6, 46., 4.4, 4.4, 8.94, 8.44, 9.4, 8., 4., 4.6,.9,.,.49 FT-IR (ATR): ν [cm - ] = 8 (w), 99 (m), 869 (m), 9 (w), 9 (w), 646 (w), 6 (w), (s), (m), 444 (w), 9 (w), 4 (w), 46 (m), 4 (m), 44 (m), 88 (w), 6 (m), (w), 699 (s) LR MS (ESI) m/z = 8.,. [M+H] +, 69. HR MS (ESI) calculated [M+H] +.86, measured.86
-(-(-Fluorophenyl)--methyl-6-nitrocyclohex--enyl)pyrrolidin--yl)methanol () C 8 H FN O, 4.8 g/mol Yield (dr trans,trans 69% (./) / cis,trans) 8 9 N 6 4 F OH NO ( MHz, CDCl ) ( MHz, CDCl ) FT-IR δ =.9 (m, 4H),.4 (s, H, H),.. (m, H, H6), 4.4 (d, J =. Hz, H),.86.69 (m, H),. (d, J =. Hz, H),.4.4 (m, H),.4. (m, H),.84 (m, H),.-. (m, H),.8 (m, H) δ = (mixture of two diastereomers) 6., 9.6,.86,.,.,.9, 9.4, 9.44, 9., 9.6, 8.,.8,.69,., 4.6,., 9.9, 8., 6.6,.96,., 9., 89.89, 6., 6.9, 6., 6.8, 6.4, 6.8, 6.49, 9.,.44, 46., 4.6,.6, 6.4, 9.48, 8.6, 6.9,., 4.69, 4.9,.4,.6,.48 (ATR): ν [cm - ] = 96 (w), 96 (m), 869 (m), 646 (m), 8 (m), (s), 48 (s), 44 (s) 48 (m), 4 (s), (m), 4 (m), 86 (m), 8 (m), (s) -(-(,4-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)pyrrolidin--yl)methanol (4) 4 C 8 H Cl N O, 8.849 g/mol Yield (dr) 6% (4//) 8 9 N 6 4 OH NO ( MHz, CDCl ) ( MHz, CDCl ) Cl Cl δ =.46 6.9 (m, H),.9 (t, J =.9 Hz, H, H6),.4 (s, H, H), 4. 4. (m, H), 4. (d, H),.6.4 (m, H),..69 (m, 4H, H),.4.6 (m, H),.8 (sbr, H) δ =(mixture of two diastereomers).8, 6.9, 6.8, 4.,.9,.,.8, 9., 9., 9.4, 8.4,.,., 8.69, 86.94, 86.84, 6.6, 6., 6.9, 6., 6.,
8.9,.6, 46.9, 4.,.8,.64, 9.6, 8.9, 4.68, 4.4,.9,.,.4 FT-IR (ATR): ν [cm - ] = 98 (w), 96 (m), 9 (m), 869 (m), 64 (w), 8 (w), 49 (s), 4 8m), 68 (m), 9 (w), (w), 4 (w), 4 (w), (w), 8 (w), 4 (m), 98 (w), 8 (w), 8 (m), 6 (m), 9 (w) HR MS (EI ev) calculated 8.6, measured 8.8 N-(-(,6-Dichlorophenyl--methyl-6-nitrocyclohex--enyl)--diphenyl-(pyrrolidin- yl)methanol (),6-Dichloro-trans-β-nitrostyrene (8 mg,. mmol), (S)-diphenylprolinol ( mg,. mmol), and -methyl--butenal ( µl,. mmol) were dissolved in toluene ( ml). The reaction mixture was stirred for h at room temperature. The solvent was removed under reduced pressure. The diastereomeric ratio was determined by H-NMR of the crude product. Column chromatography afforded a mixture of four isomers ( mg,.44 mmol, 88%, /6/.6/). The identities, relative and absolute configurations of the two major isomers (cis,trans / trans,trans = /) were established by crystal structure analysis. C H Cl N O,.468 g/mol Yield (dr) 88% (/6/.6/) TLC cyclohexane/ethyl acetate / R f =.6 Ph HO Ph 8 9 N 6 4 NO Cl ( MHz, CDCl ) ( MHz, CDCl ) major isomer (cis,trans) δ =.68 (d, H),. (d, H),. (t, H),.. (m, H),.4.9 (m, H),.8.8 (m, H),.6 (dd, J =.9 Hz,. Hz, H, H6),. (s, H, H), 4.9 (d, J = 6. Hz, H), 4.4 (d, J = 8. Hz, H), 4.8 (s, H), 4. (s, H),.6 (d, J =. Hz, H),. (s, H),.8 (s, H H8/H9/H,),.6 (dd, J =.6 Hz,.6 Hz, H, H8/H9/H),.8 (dd, J =.4 Hz, 6. Hz, H, H8/H9/H),. (s, H, HMe),.69 (m, H, H8/H9/H) δ = (mixture of diastereomers) 4.8, 46.9,.,.4, 4.9,.8,.8, 8.9, 8.8, 8. (C), 8.6 (C), 6., 6.9,.6,.46 (C),.8, 86.6, 8.6, 6.84, Cl
4., 48.,.6,.6,.4, 6.94, 4.8,.9 FT-IR (ATR): ν [cm - ] = 48 (w), 6 (w), (w), 9 (m), 9 (m), 86 (m), 9 (w), 94 (w), 4 (w), 6 (w), 9 (w), 8 (w), 4 (s), 489 (m), 446 (s), 46 (s), (s), (m), (m), 6 (w), 99 (w), (m), 48 (m), (s), 8 (s), 49 (m), (m), 99 (w), 94 (w), 99 (w), 894 (w), 84 (w), 8 (w), 9 (s), 66 (s), 4 (s), (w), 4 (s), 66 (m) Acid-mediated elimination to give nitrocyclohexadienes: A ml flask was charged with the aminocyclohexene ( mmol) in dichloromethane (4 ml). Then, benzoic acid (. mmol, for elimination of pyrrolidine) or trifluoroacetic acid ( mmol, for elimination of bulky prolinols) was added. After -6 h at room temperature, all volatiles were removed in vacuum and the crude product subjected to SiO flash chromatography (ethyl acetate/ cyclohexane). -Methyl-4-nitro--phenyl-,-cyclohexadiene (6) 6 C H NO,.4 g/mol Yield 8% TLC cyclohexane/ethyl acetate = / R f =.4 4 6 δ =.6 (d, H, H),.6.9 (m, H, Ph), 6.4.9 (m, H, ( MHz, CDCl ) H4), 4.8 (d, J =. Hz, H, H),. (dd, J = 8. Hz,.9 Hz, H, H6),.6. (m, H, H6),.89 (s, H, H) δ = 4. (C), 4. (C), 9. (CPh),.4 (C),., ( MHz, CDCl ) 8.8 (C, CPh),. (CPh), 6.6 (C, CPh),.4 (C4), 9. (C6),. (C),.8 (C) FT-IR (ATR): ν [cm - ] = 9 (s), 8 (m), (m), (s), 8 (s), 44 (m), 4 (m), 9 (m), 4 (m), 89 (s) 6 (s) LR MS (EI, ev) m/z = (M + ), 98, 8, 68, 4, 4, 8,,, 9,, 6,, 9 NO
-Methyl-4-nitro--(-fluorophenyl)-,-cyclohexadiene () C H FNO,. g/mol Yield 64% TLC cyclohexane/ethyl acetate = / R f =. 4 6 δ =. (d, H, H),. 6.96 (m, 4H, HAr),.96 (dd, J =.4 Hz, ( MHz, CDCl ).8 Hz, H, H4), 4.6 (d, J =. Hz, H, H),. (dd, J = 8.4 Hz,. Hz, H, H6),.6. (m, H, H6),.84 (s, H, H) δ = 4.46 (C), 44. (C),.4 (C), 9.4 (Ar), 8.9 ( MHz, CDCl ) (Ar),.4 (Ar), 4.4 (Ar),. (C4),.8 (Ar),.96 (C6),. (C),.8 (C) FT-IR (ATR): ν [cm - ] = 6 (w), 99 (w), 94 (w), 866 (w), 6 (w), 8 (s), (s), 486 (s), 4 (m), 44 (m), 49 (m), 8 (w), 6 (w), 6 (s), (m), (s), 99 (w), 8 (w), 9 (s), 84 (s), (m), 988 (w), 94 (w), 84 (m), 88 (m), (s), 4 (m), 9 (w) LR MS (EI, ev) m/z = (M + ), 6, 86 (M-NO ) F NO -Methyl-4-nitro--(-nitrophenyl)-,-cyclohexadiene (8) 8 C H N O 4, 6.4 g/mol Yield 66% TLC cyclohexane/ethyl acetate = / R f =.8 4 NO 8 6 NO 9 δ =.9 (m, H, H),. (d, H, H),.6 (ddd, J = 9. Hz, ( MHz, CDCl ).8 Hz,.4 Hz, H, H, H, H), 6..94 (m, H, H4),. (dd, J =. Hz,. Hz, H, H),.. (m, H, H6),.66 (dd, J = 9. Hz,. Hz, H, H6),.86 (s, H, H) δ = 4.8 (C), 4.6 (C9),.6 (C),.8 (C8),. ( MHz, CDCl ) (C, 8.4 (C), 8.9 (C),.9 (C),. (C4), 8. (C6),.6 (C),.8 (C) FT-IR (ATR): ν [cm - ] = 69 (m), 848 (m), 684 (s), 6 (m), 84 (s), (s), (s), 4 (s), 4 (s), 4 (s), 4 (s), 9 (s), (w), 8 (w), (w), 8 (w), (w), (m), 94 (m), 86 (m), 84 (m), 8 (w), 84 (m), 49 (m), 6 (s), 684
(m), 668 (s) LR MS (ESI) m/z = 8 [M+Na] +, 6, 9, HR MS (ESI) [M+Na] + calculated 8.689, measured 8.689,4-Dichloro--(-methyl--nitrocyclohexa-,4-dienyl)benzene (9) 9 C H Cl NO, 84.4 g/mol Yield % TLC cyclohexane/ethyl acetate = / R f =. 4 6 Cl NO 8 9 δ =. (d, J = 6. Hz, H, H),.44 (d, J =. Hz, H, H), ( MHz, CDCl ). (d, H, H), 6.99 (d, H, H),.9 (d, J =. Hz, H, H4), 4.8 (d, J =. Hz, H, H),. (dd, J = 8. Hz,. Hz, H, H6),.46 (d, J =. Hz, H, H6),.8 (s, H, H) δ = 4.4 (C), 44.9 (C),.9 (C8),. (C9),. ( MHz, CDCl ) (C),.88 (C),.6 (C), 8. (C),.6 (C),.6 (C4),.4 (C6),.8 (C),.8 (C) FT-IR (ATR): ν [cm - ]= 6 (w), 8 (w), 666 (w), 44 (w), 688 (s), 6 (m), 8 (s), 8 (w), (s), 466 (m), 4 (w), 46 8m), 6 (s), 89 (m), 69 (w), (w), 8 (w), (w), (w), 98 (w), 866 (w), 84 (m), 8 (m), (s), 66 (m) LR MS (EI, ev) m/z = 8, 66, 48, 6, 6,, 8, 6 HR MS (EI, ev) calculated 8.6, measured 8.8 Cl,-Dichloro--(-methyl--nitrocyclohexa-,4-dienyl)benzene (4) 4 C H Cl NO, 84. g/mol Yield 6% TLC cyclohexane/ethyl acetate = / R f =. NO 4 Cl 8 6 Cl 9 δ =.8. (m, H, H, H, H),. (t, H, H),.88 (d, J ( MHz, CDCl ) = 6. Hz, H, H4),. (t, J =. Hz, H, H),.6 (d, J =.6 Hz, H, H6),.9 (s, H, H) δ = 4. (C), 4.86 (C), 8.6 (C8), 4.4 (C, C9, C), ( MHz, CDCl ) 9. (C), 8. (C), 8. (C),. (C4),. (C), 6.9 (C6),. (C)
FT-IR (ATR): ν [cm - ] = (w), 9 (w), 84 (w), 686 (w), 6 (s), 9 (s), 46 (s), 9 (m), 8 (m), (w), 8 (m), 8 (w), 8 (s), (m) LR MS (EI, ev) m/z = 8 (M + ),, 8, 6, 8, 6, 8,, 6, 9 HR MS (EI, ev) calculated 8.6, measured 8.8 -(-Methyl--nitrocyclohexa-,4-dienyl)furan (4) 4 C H NO,. g/mol Yield % TLC cyclohexane/ethyl acetate = / R f =. 4 6 NO 8 O 9 δ =. (d, J = 6. Hz, H, H),. (d, J =. Hz, H, H), ( MHz, CDCl ) 6. (dd, J =. Hz,.9 Hz, H, H), 6. (d, J =. Hz, H, H9),.96.8 (m, H, H4), 4. (d, J = 9.4 Hz, H, H),.88 (dd, J = 8. Hz, 9. Hz, H, H6),. (dd, J = 8. Hz,. Hz, H, H6),.94 (s, H, H) δ =. (C8), 4. (C, C), 4.89 (C),.6 (C), ( MHz, CDCl ). (C4),. (C),.68 (C9),. (C6),.4 (C),.8 (C) FT-IR (ATR): ν [cm - ] = 6 (w), (w), 9 (w), 8 (w), 6 (w), 8 (s), 496 (s), 48 (m), 4 (m), (w), 64 (w), (s), 8 (s), (w), (m), (s), 8 (m), (m), (m), 989 (w), 9 (w), 898 (w), 88 (w), 8 (s), 46 (s), 6 (s), 4 (w), 68 (w) LR MS (EI, ev) m/z =, 9,, 6, 44,, 9 HPLC (Diacel ml/min, 4 nm: t R =.4 min and. min Chiralpak AS-H; n-hex/i-proh 9/) Methyl 4-nitro--phenylcyclohexa-,-diene--carboxylate (4) 4 C 4 H NO 4, 9. g/mol Yield 9% TLC cyclohexane/ethyl acetate = / R f =.8 8 O O 6 NO 4
δ =.6 (d, J = 6. Hz, H, H),..6 (m, 6H, Ph, H),. ( MHz, CDCl ) (s, H, H8),.. (m, H, H6) δ = 9.8 (C), 4. (C4), 9.4 (C), 8.98 (C, Ph),. ( MHz, CDCl ) (C),. (C), 6.64 (C, Ph),. (C8), 6.89 (C),.6 (C6) FT-IR (ATR): ν [cm - ] = 69 (w), 9 (w), 84 (w), 64 (w), 6 (w), 9 (w), 68 (s), 6 (w), 8 (w), 4 (m), 4 (m), 4 (m), (s), 9 (s), 6 (s), 8 (w), 98 (w), (w), 94 (m), 8 (w), 6 (s), 684 (w), 668 (m) LR MS (EI, ev) m/z = 9 (M + ),,, 96, 8, 6,, 4, 8,, 9,, 9 HR MS (EI ev) calculated 9.844, measured 9.8
Table: Eliminations of chiral amines. The given yields are isolated yields. The enantiomeric excess (ee) was determined by chiral GC-FID (a) or HPLC (b). Entry Starting material Acid Reaction time product Yield (ee) TMSO Ar Ar N NO TFA, 4 equiv 48h NO 4% (94%) a dr 8// 6 Ar TMSO Ar N NO TFA, equiv 48h F NO 9% (8%) a 8 F dr / Ar TMSO Ar N NO TFA, equiv. 48h Cl NO Cl 6% (9%) a 4 Cl dr 9/ Cl 9 Ar 4 TMSO Ar N 6 dr / NO O TFA, equiv. 48h 4 NO O 9% (8%) b Ph HO Ph N NO NO Cl Cl TFA, equiv 48h Cl 9 Cl % (9%) a dr /
MnO -mediated oxidation to nitrobiaryls: The nitrocyclohexadiene ( mmol, equiv.), MnO (8%, equiv.) and toluene ( ml) were combined in a reaction tube. The tube was sealed with a septum and the reaction stirred at 8 C. After 6 h, the solvent and other volatile compounds were removed by oil pump vacuum. Silica gel flash chromatography (ethyl acetate/cyclohexane) gave the aromatic product in analytically pure form. -Methyl--nitro-biphenyl (4) 4 C H NO,.9 g/mol Yield 99% TLC cyclohexane / ethyl acetate / R f =. NO 8 4 6 9 δ =.8 (d, J = 8. Hz, H, H),..9 (m, H, H, H4),.6 ( MHz, CDCl ). (m, H, Ph),.4 (s, H, Me) δ = 4. (C6), 4. (C4),.9 (C), 6. (C),. ( MHz, CDCl ) (C4), 8.8 bis.9 (6C, Ph), 4. (C),. (Me) -Fluoro--methyl--nitrobiphenyl (44) 44 C H FNO. g/mol Yield 99% TLC cyclohexane/ethyl acetate = / R f =.4 NO 4 8 6 F 9 δ =.99 (d, J = 8. Hz, H, H),.4. (m, H),.. (m, ( MHz, CDCl ) H),..9 (t, H, H),. (s, H, H) δ = 6.94 (C9), 46.4 (C), 44.6 (C),. (C6),.68 ( MHz, CDCl ) (C),. (C8), 9.98 (C4), 9.4 (C), 4.69 (C), 4.49 (C), 4.4 (C),.9 (C),.4 (C) FT-IR (ATR): ν [cm - ] = 64 (w), 9 (w), 8 (w), 6 (w), 86 (w), 8 (s), 44 (m), 4 (s), 8 (w), 4 (w), (m), (w), (w), 4 (w), 89 (w), 86 (s), 8 (m), (s), 696 (w) LR MS (EI, ev) m/z = (M + ),, 86, 8,,, 99,, 6 HR MS (EI ev) calculated.69, measured.
-Methyl-, -dinitrobiphenyl (4) 4 C H N O 4, 8. g/mol Yield 86% (by H-NMR) TLC cyclohexane/ethyl acetate = / R f =.8 4 NO 8 6 NO 9 δ = 8. (d, H, H), 8.6 (d, H, H),.68 (d, H, H ),.8 (t, ( MHz, CDCl ) H, H),.9 (d, H, H),.4.8 (m, H, H4),.8 (d, H, H6),.48 (s, H, H) δ = 44.8, 4.9, 4.,.,.4,.8, 9.6, 8.9, ( MHz, CDCl ) 4.9, 4.,.44 (C) FT-IR (ATR): ν [cm - ] = 8 (w), 9 (w), 8 (w), 64 (m), 86 (m), (m), 9 (s), 4 (s), (w), (w), 4 (w), 9 (w), 889 (w), 8 (w), 89 (m), 86 (m), 49 (m), 698 (m), 668 (m), 6 (w) LR MS (EI, ev) m/z = (M-NO ), 8,, 8,, 89,, 6 -(-Methyl--nitrophenyl)benzo[d][,]dioxole (46) 46 C 4 H NO 4,.4 g/mol Yield % TLC cyclohexane/ethyl acetate = / R f =. 4 6 8 NO 9 O O 4 δ =. (d, H, H),..4 (m, H, H4, H6), 6.9 6.69 (m, ( MHz, CDCl ) H, H9, H, H), 6. (s, H, H4),.4 (s, H, H) δ = 4.84 (C), 4.9 (C), 44.9 (C), 4. (C), 4.8 ( MHz, CDCl ) (C),. (C8),.4 (C6), 8.4 (C4), 4. (C),. (C), 8. (C, C9, C),. (C4),.8 (C) FT-IR (ATR): ν [cm - ] = 9 (m), 8 (w), (s), 46 (s), 44 (m), 4 (m), 9 (s), 8 (w), 8 (s), 9 (w), 8 (w), 8 (m), 8 (w), 64 (w) LR MS (EI, ev) m/z = (M + ),, 4,, 89,, 6 HR MS (EI, ev) calculated (M + ).688, measured.69
,4-Dichloro- -methyl- -nitrobiphenyl (4) 4 C H 9 Cl NO, 8. g/mol Yield 48% TLC cyclohexane/ethylacetate = / R f =. 4 8 6 Cl NO 9 δ = 8. (d, H, H),.46 (s, H, H6),.4. (m, H, H, ( MHz, CDCl ) H),.9 (d, H, H4),. (s, H, H),.48 (s, H, H) δ = 46. (C), 44., 6., 4.49,.,.4,.4, ( MHz, CDCl ).,.,., 9.84, 9., 8.,.49,., 4.8,.8,.4 (C) FT-IR (ATR): ν [cm - ] = 9 (w), 69 (w), 86 (m), 9 (s), 466 (m), (w), 4 (s), (m), 66 (w), (w), 888 (w), 866 (w), 8 (s), 9 (s), 9 (m), 688 (w) LR MS (EI, ev) m/z = 48/46 (M-Cl), 6, 6, 4,, 9, 8, 69,, Cl Zn/HCl-mediated reduction of cyclohexenyl amines: R N R R R N HCl aq. /Zn NO NH EtOH R R 4 R R 4 The 6-nitrocyclohexenyl amine (.4 mmol,. equiv.) was dissolved in ethanol (. ml) and aqueous HCl (6 N,. ml) was added. Zinc powder (6 mg, 4. mmol, equiv.) was added in small portions and the reaction mixture was stirred for h at room temperature. After addition of saturated aqueous NaHCO ( ml), the solution was extracted with CH Cl ( ml), the combined organic layers were dried Na SO 4 ) and concentrated under reduced pressure to give the diamine in >9% purity and yield. 48: N NH Yield: 98% C 6 H N, 4,g/mol
Condition: m.p.: pale yellow solid 6 C decomp. ( MHz, CDCl ) δ =.44. (m, H),.. (m, H), 6. 6.6 (m, H),..6 (m H),..6 (m, H),.4.86 (m, 6H),.6 (s, H),.4.8 (m, H),..6 (m, 4H). ( MHz, CDCl ) δ = 9.8,., 9.6, 8., 8.,., 64.,.6, 4., 4.,.. FT-IR (ATR): ν [cm - ] = 4, 8, 966, 9, 496, 4,, 9, 6, 9, 89, 69, 48,, 64, 96, 66,,, 469 EI-MS ( ev): [MH] + = 4.86; calculated: 4,86 49: N NH Cl Cl Yield: 9% Condition: m.p.: C H Cl N,,8 g/mol colourless solid C decomp. ( MHz, CDCl ) δ =.4 (dd,.4 Hz, H),.4 (dd,.4 Hz, H),. (t, H),.4 (s, H), 4.8.8 (m, H),.64.49 (m, H),.6. (m, H),.. (m, H),..6 (m, H),.. (m, H),..89 (m, 4H),.8 (s, H). ( MHz, CDCl ) δ = 4.,., 4.,.4,., 9.9, 9.6, 4.6, 6.,.8,., 46., 44.,.6,.4,.. FT-IR (ATR): ν [cm - ] = 968, 88, 8, 6, 4,, 8, EI-MS ( ev): 999, 96, 869, 9, 6,, 689, 6, 6, 8,, 4, 48, 446 [M * ] + = 4.8; [M + H] + =,8; calculated:.
N,N -Diallyl--methyl-,,,6-tetrahydro-[,'-biphenyl]-,-diamine () N NH Yield: 99% Condition: m.p.: C 9 H 6 N, 8,4 g/mol pale yellow solid 99- C ( MHz, CDCl ) δ =.9 -.4 (m, H), 6. 6. (m, H),.64.4 (m, H),.. (m, 4H),. (d, J =. Hz, H),.8. (m, H),.4.4 (m, H),..98 (m, H),.46.4 (m, H),. (s, H). ( MHz, CDCl ) δ = 9.8, 9.6, 9., 8.,.9, 6.,.4, 4., 8.6,.. FT-IR (ATR): ν [cm - ] = 9, 6, 44,, 98, 6, 998, 96, 84, 6,, 64, 64, 4, 6, 46 EI-MS ( ev): [M] + = 8.96; calculated: 8.96
Three-component cyclisation with carboxamides: A ml pressure tube was charged with the carboxamide, unsaturated aldehyde, and nitroalkene (each mmol) and toluene ( ml) and heated to C in an oil bath. After 6 h, the volatile components were removed by vacuum distillation. The viscous residue was treated with cold diethylether ( ml) upon which a white precipitate formed. The solids were collected and dried in vacuum. N--Methyl-(6-nitro--phenylcyclohex--enyl)acetamide () C H 8 N O, 4. g/mol Yield (dr cis,trans / 66% (8/) trans,trans) TLC cyclohexane/ethyl acetate = / R f =. m.p. C O 8 NH 6 4 δ =.4.9 (m, H, Ph),.9 (d, H, NH),.4 (d, J =. Hz, ( MHz, CDCl ) H, H),.4. (m, H, H6),. (dd, J =. Hz, 4.9 Hz, H, H),. (td, J =. Hz, 6. Hz, H, H4),.4 (dd, J = 8.4 Hz, 6. Hz, H, H),.4 (dd, J = 8. Hz,. Hz, H, H),.98 (s, H, H8),. (s, H, Me) δ = 69.4 (C), 9.94 (C), 8.8 (Ph), 8.9, (C, Ph), ( MHz, CDCl ).6 (Ph),. (C, Ph), 8.8 (C), 88. (C), 4.6 (C6), 9.88 (C4),. (C),.9 (C8),.8 (Me) FT-IR (ATR): ν [cm-] = (w), (w), 9 (w), 9 (w), (w), 64 (s), 49 (s), 4 (w), 48 (w), 69 (m), 8 (w), 46 (w), (w), 9 (w), 9 (w), 8 (w), 8 (w), 8 (w), 8 (m), 699 (m) LR MS (EI, ev) m/z = 4 (M + ), (M-NO ) HR MS (ESI) calculated (M+Na + ) 9., measured 9. NO Ph
N-(-(,6-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)acetamide () C H 6 Cl N O, 4. g/mol Yield (dr cis,trans / trans,trans) 6% (/) TLC cyclohexane/ethyl acetate = / m.p. ( MHz, CDCl ) ( MHz, CDCl ) R f =.6 C (decomp.) 9 8 O NH 6 4 Cl NO Cl δ =. (d, H, Ar),. (d, H, Ar),.4 (t, H, Ar), 6. (dd, J =.6 Hz, 4.8 Hz, H, H),.6 (d, J = 8.9 Hz, H, NH),. (d, J = 4.8 Hz, H, H),.46.4 (m, H, H6), 4.4 (td, J =. Hz, 6. Hz, H, H4),.8 (dd, J = 8. Hz,. Hz, H, H),.9 (dd, J = 8. Hz, 6. Hz, H, H),. (s, H, H8),.8 (s, H, H9) δ = 69.68 (C), 8.6 (C),.4 (Ar),.89 (Ar),. (Ar),.4 (Ar), 9.9 (Ar), 8.8 (C), 84.9 (C), 46. (C6), 6.6 (C4),.84 (C),.6 (C8),.8 (C9) FT-IR (ATR): ν [cm-] = 64 (m br ), 44 (w), 9 (w), 9 (w), (w), 66 (s), 8 (m), 49 (s), 46 (s), (s), 8 (m), 84 (m), 6 (w), (w), (w), 8 (w), 6 (w), 96 (w), 9 (w), 86 (w), 9 (s), 66 (s), (m) LR MS (ESI) m/z = 6 (M+Na) +, 8 (M+Na-NO ) +,, 6 HR MS (ESI) [M+Na] + calculated 6.4, measured 6.4 N-(-(,4-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)acetamide () C H 6 Cl N O, 4. g/mol Yield (dr cis,trans / trans,trans) % (8/) TLC cyclohexane/ethyl acetate = / m.p. R f =. 4 48 C 9 8 O NH 6 4 Cl NO Cl
δ =.4 (dd,.9 Hz, H, Ar),. (dd,. Hz, H, Ar),. (d, ( MHz, CDCl ) H, Ar),.8 (d, J = 8.9 Hz, H, NH),.4 (s, H, H),.4 (s, H, H6),.6 (dd, J =. Hz, 4.8 Hz, H, H), 4.6 (ddd, J =.8 Hz, 8. Hz,. Hz, H, H4),. (dd, J = 8.4 Hz, 6. Hz, H, H),.. (m, H, H),. (s, H, H8),.6 (d, J = 9.6 Hz, H, H Me) δ = 6.4 (C), 8.46 (C), 6.4 (Ar), 4.6 (Ar), 4. ( MHz, CDCl ) (Ar),.6, (Ar),.8 (Ar), 8. (Ar), 9. (C), 86. (C), 4. (C6), 6.8 (C4),.6 (C),. (C8),.4 (C9) FT-IR (ATR): ν [cm-] = 4 (m), (m), (w), 9 (w), 68 (s9, 8 (w), (s), 46 (m), (m), 8 (m), (m), 6 (w9, 4 (w9, 9 (w), 866 (w), 84 (m), 8 8w), 6 (m) LR MS (ESI) m/z = 6 (M+Na + ), 8,, 6 HR MS (ESI) calculated [M+H] + 4.6, measured 4.64; N-(-(4-Fluorophenyl)--methyl-6-nitrocyclohex--enyl)acetamide (4) 4 C H FN O, 9. g/mol Yield (dr cis,trans / trans,trans) 44% (/) TLC cyclohexane/ethyl acetate = / R f =. m.p. 4 C ( MHz, CDCl ) ( MHz, CDCl ) 9 8 O NH 6 4 F NO δ =.8 6.96 (m, 4H),.4 (d, J = 8.8 Hz, H, NH),. (d, J =. Hz, H, H),.9 (dd, J = 9. Hz,. Hz, H, H6),. (dd, J =.9 Hz, 4.9 Hz, H, H),.8 (td, J =. Hz, 6. Hz, H, H4),.4 (dd, J = 8. Hz,.9 Hz, H, H),.9 (dd, J = 8. HZ, 9.9 Hz, H, H),. (s, H, H8),.8 (s, H, H9) δ = 69.6 (C), 8.8 (C), 9.4 (Ar), 8. (Ar), 6.8 (Ar), 4.89 (Ar), 8.9 (C), 6.49 (Ar), 6. (Ar), 86.48 (C), 4.6 (C6),.9 (C4), 4. (C),. (C8),.6 (C9)
FT-IR (ATR): ν [cm-] = 69 (w), (w), 96 (w), 9 (w), (w), 64 (s), (s), 49 (w), 48 (w), (m), 8 (w), 4 (w), 9 (w), 9 (w), 9 (w), 88 (w), 8 (w), 8 (w), 8 (m), 69 (m) LR MS (EI ev) m/z = 9 (M + ), 46, N-(6-Nitro--phenylcyclohex--enyl)acetamide () C 4 H 6 N O, 6.9 g/mol Yield (dr cis,trans / % (8:) trans,trans) m.p. 66 C (mixture of two diastereomers) TLC (ethyl acetate) : R f =.48 O 9 8 NH 4 NO 6 IR (ATR), /λ [cm - ] = (w), (w), 6 (s), 4 (s), (m), 6 (m), (w), 96 (m), 699 (s) H-NMR ( MHz, CDCl ), major diastereomer, δ =.4 (m, H, H-Arom.),.9 (d, H, J = 9. Hz, H-),.6 (m, H, H-4, H-),. (m, H, H-),. (dd, H, J =./4.89 Hz, H-),.4 (m, H, H-),. (dt, H, J = 8.88 Hz, J = 4.89 Hz, H-6),.8 (dd, H, J = 8.88 Hz, J = 8.4 Hz, H-6 ),.98 (s, H, H-9) C-NMR ( MHz, APT, CDCl ), major diastereomer, δ = 69. (C-8), 9.8 (C-), 9,, 9., 9.,.9,.6,., 4. (C-4, C-, C-, C-, C-, C-, C-), 88. (C-), 4. (C-), 4. (C-),. (C-6),. (C-9) GC/MS (-M), R t : 9.84 min, m/z = 6 [M] +, [M-NO ] +, 94, [M-CH CO-NO ] +, [M-CH CONH-NO ] +, 9,, 9, HR MS (ESI, [u]) measured: 8. [M+Na] +, calculated: 8. N-(4-Methyl-6-nitro--phenylcyclohex--enyl)acetamide (6) 6 C H 8 N O, 4. g/mol Yield (dr cis,trans / 9% (d.r. > /) trans,trans) m.p. C O 9 8 4 NH 6 NO TLC (ethyl acetate) : R f =.4 4
IR (ATR), /λ [cm - ] = 8 (w), 96 (w), 6 (s), (s), 4 (m), (m), 8 (w), (w), 9 (w), (m) H-NMR ( MHz, CDCl ), δ =.6 -.9 (m, H, Ar),.8 (m, H, H-),.6 (dd, H, J =.4/. Hz, H-4, H-),.6 (m, H, H-),.6 (dd, H, J =.4/.4 Hz, H-),.8 (dd, H, J =.4/.8 Hz, H-),.4 (m, H, H-6),. (s, H, H-9),.9 (d, H, J =. Hz, H-4) C-NMR ( MHz, APT, CDCl ), δ = 69.9 (C-8), 8.8 (C-), 6. (C-), 8.9, 8.8, 8., 8.,.8 (C-, C-, C-, C-, C-),.8 (C-4), 88.6 (C-), 4. (C-), 4.6 (C-), 8. (C-6),. (C-9), 9. (C-4) LR MS (positive ESI, MeOH/CH Cl ), m/z = 9 [M+Na] +,, 4 HR MS (ESI, [u]) measured: 9. [M+Na] +, calculated: 9. N-(,4-Dimethyl-6-nitro--phenylcyclohex--enyl)acetamide () C 6 H N O, 88.4 g/mol Yield (dr cis,trans /.6 g, 4% (d.r.>4:) trans,trans) m.p. C TLC ethyl acetate/cyclohexane :), R f =. O 9 8 NH 4 NO 6 IR (ATR), /λ [cm - ] = (w), 9 (w), (m), 6 (s), (s), 44 (m), (s), 4 (s), 4 (m), 9 (w), (m) H-NMR ( MHz, CDCl ), δ =.6 -.9 (m, H, Ar),.64 (d, H, J = 9.6 Hz, H-),. (s, H, H-),.6 (m, H, H-),. (dd, H, J =./4.86 Hz, H-),.8 (dd, H, J =./. Hz, H-),.6 (m, H, H-6),. (s, H, H-9),.8 (s, H, H-),.9 (d, H, J = 6.9 Hz, H-) C-NMR ( MHz, APT, CDCl ), δ =. (C-8), 8.9 (C-),. (C-),. (C-4), 8.9, 8.,. ( C, Ar), 89. (C-), 49. (C-), 46. (C-), 8. (C-6),. (C-9),.6 (C-), 9. (C-) LR MS (positive ESI, MeOH/CH Cl ), m/z = 89 [M+H] +, 4 [M-NO ] +,, 8, HR MS (ESI, [u]) measured: 89.4 [M+H] +, calculated: 89.
-(6-Nitro--phenylcyclohex--enyl)pyrrolidin--one (8) 8 C 6 H 8 N O, 86.6 g/mol Yield (dr cis,trans / 6% (6/) trans,trans) TLC cyclohexane/ethyl acetate = / R f =. m.p. 8 C O 8 9 δ =. (dt, H, Ph), 6. (dd, J = 9.6 Hz,. Hz, H, H),.6 ( MHz, CDCl ) (d, J = 9.8 Hz, H, H),.4 (d, J =. Hz, H, H6),. (dd, J =.6 Hz,.9 Hz, H, H),. (dd, J =.6 Hz,.9 Hz, H, H),. (dq, J = 8. Hz,.6 Hz, H, H, H),.6 (dd, J = 4. Hz, 9.4 Hz, H, H),..4 (m, H, H, H8),..88 (m, H, H9) δ =.6 (C), 9.9 (Ph),.64 (C), 8.96 (C, Ph),. ( MHz, CDCl ) (Ph),.6 (C, Ph),.6 (C), 89. (C), 4.6 (C6), 4.8 (C), 4.49 (C4),.4 (C),. (C8), 8.8 (C9) FT-IR (ATR): ν [cm - ] = 9 (w), 888 (w), 8 (w), 9 (w), 68 (s), 48 (s), 49 (w), 4 (w), 4 (s), 8 (m), 66 (m), 89 (w), 6 (w), (w), 6 (m), 46 (m), (m) LR MS (EI, ev) m/z = 4 (M-NO ),,,, 86 N 6 4 NO Ph -(-Methyl-6-nitro--phenylcyclohex--enyl)pyrrolidin--one (9) 9 C H N O,. g/mol Yield (dr cis,trans / trans,trans) 9 % (/) TLC cyclohexane/ethyl acetate = / R f =. m.p. -6 C ( MHz, CDCl ) O 8 9 N 6 4 NO δ =.4. (m, H, Ph),.49 (d, J =. Hz, H, H6),. (d, J =. Hz, H, H),.9 (dd, J =.6 Hz, 6. Hz, H, H),.8.6 (m, H, H),.6.4 (m, H, H4, H),. (ddd, J =. Hz, 6.9 Hz, 8.6 Hz, 4H, H, H),..88 (m, H, H8),.8 (s, H, Me) δ =.6 (C), 4. (C), 9.96 (Ph), 8.9 (C, Ph),.64 Ph
( MHz, CDCl ) (Ph),. (Ph),. (C, Ph), 6.86 (C), 88.8 (C), 4. (C6), 4.88 (C8), 4.8 (C4), 8. (C),.84 (C),. (Me), 8.8 (C9) FT-IR (ATR): ν [cm-] = 969 (w), 9 (w), 8 (w), 688 (s), 48 (s), 49 (w), 4 (m), 4 (m), (w), 84 (m), 6 (m), 94 (w), (w), 8 (w), 88 (w), 84 (w), 8 (w), 6 (m), (m) HR MS (EI, ev) calculated.44, measured.4 N-(-(,4-Dichlorophenyl)--methyl-6-nitrocyclohex--enyl)acetamide (6) 6 C 8 H N O, 4.8 g/mol Yield (dr cis,trans / trans,trans) 8% (/), stereochemistry at C not determined TLC cyclohexane/ethyl acetate = / ( MHz, CDCl ) ( MHz, CDCl ) R f =.9 O 8 9 N 6 4 NO δ = (major isomer).4. (m, 6H),. (s, H, H),. (d, J =.4 Hz, H, H6),. (dd, J =.9,.8 Hz, H, H),. (dt, J =.,.9 Hz, H, H),.48 (s, H, H, H4),. (td, J = 8., 4. Hz, H),..9 (m, H),.6. (m, H),.48 (s, H, HMe),.94 (s, H, Me). δ = 6., 8.8,.6,., 8.4, 8.6,.9,.68,.44, 89.6, 8., 6.4,.9, 48.4, 4.,.4, 6.6,.9,.4,.4, 9., 4.. FT-IR (ATR): ν [cm - ] = 9 (w), 9 (w), 96 (m), 99 (m), (w), 689 (s), 49 (s), 494 (m), 4 (m), 4 (s), (m), 8 (s), 66 (s), 9 (w), (w), 866(w), 84 (w),66 (m),6 (m), (m), (s) LR MS (EI ev) 4, 68,, 8, 6 HR MS (EI ev) calculated 4.6, measured: 4.6 Ph