Supporting Information

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1 Supporting Information Wiley-VCH 00 1 Weinheim, Germany

2 SUPPLEMETARY MATERIAL Pericyclic Cascade Reactions of C-Bicyclo[1.1.0]butylbenzylamines Peter Wipf,* and Maciej A. A. Walczak Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 10 Experimental procedures and spectral data for new compounds. OESY spectrum for 1.

3 General Methods. All moisture-sensitive reactions were performed under an atmosphere of and glassware was flame dried under vacuum prior to use. THF was dried by distillation over a/benzophenone and i- Pr H was dried by distillation over CaH. Toluene and CH Cl were purified by filtration through activated alumina. Me Zn (.0 M in toluene) and Et Zn (neat) were purchased from the Aldrich Chemical Company. 3- bromo-1-phenylpropyne, cyclopropylallyl bromide and (Z)-cinnamyl bromide were obtained from 1-phenyl-1- propyn-3-ol, 1 cyclopropylallyl alcohol and (Z)-cinnamyl alcohol, 3 respectively, via reaction with 3 P Br /imidazole in CH Cl at 0 ºC.,-Dibromo-1-(chloromethyl)-1-phenylcyclopropane 3, CH=P(O), t-buch=p(o), and c-c H 11 CH=Ts were prepared according to literature protocols. Unless otherwise stated, solvents or reagents were used as received. Analytical thin layer chromatography (TLC) was performed on pre-coated silica gel 0 F- plates (particle size mm, mesh) and visualization was accomplished with a nm UV light and/or by staining with Vaughn's reagent (. g of (H ) Mo O H O and 0.0 g of Ce(SO ) in 100 ml of 3. H SO solution). MR spectra were recorded at 300 MHz/ MHz ( 1 H MR/ 13 C MR) or 00 MHz/1 MHz ( 1 H MR/ 13 C MR) using Bruker AVACE 300 MHz or Bruker AVACE 00 MHz spectrometers at 1 C. Chemical shifts (δ) are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad), coupling constants, and integration. IR spectra were obtained on a icolet AVATAR 30 FT-IR E.S.P. spectrometer. Mass spectra were obtained on a Micromass Autospec double focusing instrument. Melting points were recorded on Mel-Temp II apparatus and are uncorrected. Microwave reactions were run on a Personal Chemistry workstation. H O P 1 3 1a CO Me -(3-(-Methoxycarbonylphenyl)-1-phenylprop--ynyl)-P,P-diphenylphosphinamide (1a). General Protocol A. A suspension of CuI (0.1 g, 0.1 mmol) and Pd(P 3 ) (0. g, 0. mmol) in degassed i-pr H (100 ml) was cooled to 0 o C and treated with methyl -iodobenzoate (. g,.1 mmol). A solution of alkyne 0 (3.0 g,.1 mmol) in THF ( ml) was added via syringe and the reaction mixture was vigorously stirred at 0 o C for 1. h, quenched with sat. H Cl, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and concentrated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded 1a (. g, %) as a colorless solid: Mp o C (hexanes/ch Cl ); IR (KBr) 1,, 11, 10, 13, 11, 13, 10, 130, 1, 11, 11, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ (m,

4 H),. (d, J =.3 Hz, H),.0-.3 (m, H),. (d, J =. Hz, H),.-.30 (m, 11 H),. (app t, J =. Hz, 1 H, H), 3. (s, 3 H, CH 3 ), 3. (b t, J =. Hz, 1 H, H 1 ); 13 C MR ( MHz, CDCl 3 ) δ 1.0 (CO), 13.0, 133.1, 13., 13., 131., 131., 131.1, 131.3, 131.0, 1.1, 1.30, 1., 1., 1.3, 1.0, 1.31, 1.1, 1.0 (d, J =. Hz, C ),.3 (C 3 ),.1 (OCH 3 ),.00 (C 1 ); MS (EI) m/z (rel intensity) (M +, ), 3 (1), 330 (), (), 01 (100); HRMS (EI) calc for C H O 3 P.1, found.10. H O P 1 3 1b C -(3-(-Cyanophenyl)-1-phenylprop--ynyl)-P,P-diphenylphosphinamide (1b). According to the General Protocol A, alkyne 0 (0.0 g, 1. mmol), -iodobenzonitrile (0.33 g, 1. mmol), CuI (0.0 g, 0.1 mmol) and Pd(P 3 ) (0.0 g, 0.0 mmol) in i-pr H ( ml) and THF (10 ml) afforded 1b (0.0 g, %) as a colorless solid: Mp o C (hexanes/etoac); IR (KBr) 33, 31,, 103, 13, 11, 11, 1110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.10 (dd, J = 1.1,. Hz, H),.1 (dd, J = 1.0,.0 Hz, H),.1 (d, J =.3 Hz, H),.-.3 (m, 13 H),. (app t, J =. Hz, 1 H, H),.0 (app t, J =.0 Hz, 1 H, H 1 ); 13 C MR ( MHz, CDCl 3 ) δ 13., 13., 13., 13., 13.3, 13.0, 131.1, 131.1, 131., 131., 131., 131.1, 1., 1., 1., 1.0, 1., 1.0, 11. (C), 111., 3. (d, J =.0 Hz, C ), 3. (C 3 ),. (C 1 ); MS m/z (rel. intensity) 3 (M +, ), 3 (), 3 (1), 30 (3), (), 31 (), 01 (100), 1 (1); HRMS (EI) calc for C H 1 OP 3.13, found H O P 1 3 1c -(1-enyl-3-(pyridin-3-yl)prop--ynyl)-P,P-diphenylphosphinamide (1c). According to the General Protocol A, alkyne 0 (.0 g,.0 mmol), 3-iodopyridine (1. g,.0 mmol), CuI (0.11 g, 0.0 mmol) and Pd(P 3 ) (0.3 g, mmol) in i-pr H (100 ml) and THF (0 ml) were stirred at 0 ºC for. h. The reaction mixture was quenched with sat. H Cl and extracted (3x) with EtOAc. The combined organic layers 3

5 were washed with water and brine, dried (a SO ) and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:10) afforded 1c (1. g, %) as a colorless oil that solidified upon standing: IR (neat) 311, 30, 10, 1, 1, 1, 13, 11, 130, 1, 11, 113, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.-. (m, H),.1 (dd, J = 1.1,. Hz, H),.3 (dd, J = 1.1,.0, H),.-.1 (m, H),.1-.3 (m, H),.31-. (m, H),. (app t, J =. Hz, 1 H, H 1 ),.01 (app t, J =. Hz, 1 H, H); 13 C MR ( MHz, CDCl 3 ) δ 11., 1.30, 13., 13., 13.1, 133.0, 13., 13., 13.3, 131., 131.3, 131.0, 131.3, 131.0, 1., 1.3, 1., 1.1, 1., 1.03, 1.0, 11.,. (d, J =. Hz, C ), 1. (C 3 ),. (C 1 ); MS (EI) m/z (rel. intensity) 0 (M +, ), 331 (), 30 (13), 3 (1), 0 (100), 01 (), 1 (1); HRMS (EI) calc for C H 1 OP 0.13, found H 1 P(O) 3 a CO Me -((3-(-Methoxycarbonylphenyl)bicyclo[1.1.0]but-1-yl)(phenyl)methyl)-P,P-diphenylphosphinamide (a). General Protocol B. Amide 1a (1.0 g,. mmol) was dissolved in dry CH Cl (0 ml), cooled to 0 o C and treated with Me Zn (1.1 ml,. mmol,.0 M in Me). After 1 h at 0 oc, the reaction mixture was cooled to 0 o C and transferred via cannula into a cold (-0 o C) solution of (CH I) Zn prepared by the addition of CH I (0. ml,. mmol) to a solution of Et Zn (0.3 g,.3 mmol) in CH Cl (0 ml) at -0 o C. The reaction mixture was warmed to 0 o C, stirred for 30 min, and quenched with sat. H Cl. Extraction with EtOAc followed by purification by chromatography on SiO (hexanes/etoac, 1: to 1:) afforded a (0. g, %) as a colorless solid: Mp ºC (hexanes/ch Cl ); IR (KBr) 33, 3, 30, 31, 1, 10, 10, 13, 1, 11, 111 cm -1 ; 1 H (300 MHz, CDCl 3 ) δ.00 (dd, J = 11.,.0 Hz, H),. (d, J =. Hz, H),. (dd, J = 11.3,. Hz, H),.-.3 (m, 3 H),.-.3 (m, 3 H),.1-.0 (m, H),.0 (d, J =.3 Hz, H),. (d, J =.0 Hz, H),.0 (app t, J =. Hz, 1 H, H 1 ), 3. (s, 3 H, OCH 3 ), 3. (dd, J =.,. Hz, 1 H. H),.3 (d, J =. Hz, 1 H, H 3exo or H exo ), 1. (d, J =. Hz, 1 H, H exo or H 3exo ), 1.00 (s, 1 H, H 3endo or H endo ), 0.3 (s, 1 H, H endo or H 3endo ); 13 C MR ( MHz, CDCl 3 ) δ 1. (CO), 1.1, 13.1, 13.3, 13.0, 131., 131., 131.0, 131.3, 131., 1.13, 1., 1.1, 1.1, 1.0, 1., 1., 1.0, 1.0, 1.,. (C 1 ), 1. (OCH 3 ), 3.0 (C 3 or C ), 31.1 (C or C 3 ), 30. (d, J =.1 Hz, C ), 0. (C ); MS (ES) m/z (rel. intensity) 1 ([M+a] +, 100), 13 (), 31 (10), 301 (1), (1), 1 (), 01 (); HRMS (ES) calc for C 31 H ao 3 P (M+a) 1.10, found 1.1.

6 H 1 P(O) 3 b C -((3-(-Cyanophenyl)bicyclo[1.1.0]but-1-yl)(phenyl)methyl)-P,P-diphenylphosphinamide (b). According to General Protocol B, amide 1b (1.1 g,. mmol) and Me Zn (1.3 ml,. mmol,.0 in Me) in CH Cl ( ml) were reacted with (CH I) Zn prepared by the addition of CH I (0.3 ml, 10 mmol) to the solution of Et Zn (0. g,. mmol) in CH Cl ( ml) at -0 o C. The reaction mixture was stirred at 0 o C for 1 h, quenched with sat. H Cl, and extracted (3x) with CH Cl. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded b (0.1 g, 3%) as a colorless foam: IR (KBr) 300, 30, 30, 3, 10, 13, 11, 113 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ. (ddt, J = 1.0,., 1. Hz, H),.1 (ddt, J = 1.1,., 1. Hz, H),.-.0 (m, H), (m, H),.0 (dd, J =., 1. Hz, H),. (dd, J =., 1. Hz, H),.0 (app. t, J =. Hz, 1 H, H 1 ), 3. (dd, J =.,. Hz, 1 H, H),.1 (dd, J =., 1.1 Hz, 1 H, H 3exo or H exo ), 1. (dd, J =., 0. Hz, 1 H, H exo or H 3exo ), 0. (s, 1 H, H 3endo or H endo ), 0. (s, 1 H, H endo or H 3endo ); 13 C MR ( MHz, CDCl 3 ) δ 1., 13., 13.0, 133., 13.0, 13.0, 131., 131.0, 131., 131.0, 1.3, 1.3, 1., 1.0, 1.13, 1., 1., 1., 11. (C), 10.1,. (C 1 ), 3. (C 3 or C ), 31.0 (C or C 3 ), 31. (d, J =. Hz, C ), 0. (C ); MS (EI) m/z (rel. intensity) 0 (M +, ), 3 (), 30 (1), (100), 3 (3), 01 (); HRMS (EI) calc for C 30 H OP 0.10, found H 1 P(O) 3 c -((3-(Pyridin-3-yl)bicyclo[1.1.0]but-1-yl)(phenyl)methyl)-P,P-diphenylphosphinamide (c). According to General Protocol B, amide 1c (0.0 g, 1. mmol) and Me Zn (0.1 ml, 1. mmol,.0 in Me) in CH Cl (0 ml) were reacted with (CH I) Zn prepared by the addition of CH I (0.0 ml,. mmol) to a solution of Et Zn (0.30 g,. mmol) in CH Cl (0.0 ml) at -0 ºC. The reaction mixture was stirred at 0 ºC for 1 h, quenched with sat. H Cl, and extracted (3x) with CH Cl. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac/meoh, 1::1) afforded c (0.1 g, 0%) as a colorless foam: IR (neat) 30,, 11, 10, 1, 1, 13, 10, 1311, 111,

7 113, 1110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.1 (d, J = 3. Hz, 1 H),. (bs, 1 H),.0 (ddd, J = 11.,.0, 1. Hz, H),. (dd, J = 1.0,.1 Hz, H),.-.0 (m, H), (m, 3 H),. (dd, J =.,. Hz, 1 H),.0 (d, J =. Hz, 1 H),. (t, J =.3 Hz, 1 H, H 1 ), 3. (app t, J =. Hz, 1 H, H),.1 (d, J =. Hz, 1 H, H 3exo or H exo ), 1.0 (d, J =. Hz, 1 H, H exo or H 3exo ), 0.0 (s, 1 H, H 3endo or H endo ), 0.0 (s, 1 H, H endo or H 3endo ); 13 C MR ( MHz, CDCl 3 ) δ 1., 1.0, 13., 13., 133.0, 13., 13.1, 13.0, 131., 131.3, 131.1, 131.3, 1.3, 1., 1., 1.1, 1.11, 1.0, 1., 1.3, 1.,.01 (C 1 ), 33. (C 3 or C ), 30. (C or C 3 ),. (d, J =. Hz, C ), 1.0 (C ); MS (EI) m/z (rel. intensity) 3 (M +, 3), 33 (1), 30 (), 3 (1), 1 (1), 01 (0), (100); HRMS (EI) calc for C H OP 3.10, found O H S O d Me Cyclohexyl(3-phenylbicyclo[1.1.0]but-1-yl)--tosylmethanamine (d). General Protocol C.,-Dibromo-1- (bromomethyl)-1-phenylcyclopropane 3 (0.0 g, 1. mmol) was dissolved in Et O (10.0 ml), cooled to o C and treated with MeLi (0. ml, 1. mmol, c = 1. M in Et O). The reaction mixture was allowed to warm up to 0 o C over 1 h, cooled to o C and treated with t-buli (0.1 ml,. mmol, c = 1. M in pentane). After 1 h at o C, a solution of c-c H 11 CH=Ts (0.1 g, 0. mmol) in THF (.0 ml) was added, the reaction mixture was stirred for 10 min, warmed up to rt, quenched with sat. H Cl, and extracted (3x) with EtOAc. The combined organic layers were washed with water, brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, :1) afforded d (0.1 g, %) as a light yellow oil: IR (neat) 3,, 3, 101, 1, 13, 11 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.0-. (m, H),.31-. (m, H),.-.10 (m, H),.0 (d, J =.0 Hz, 1 H, H), 3.3 (dd, J =.0, 3. Hz, 1 H, H 1 ),.1 (s, 3 H, CH 3 ), 1. (d, J =. Hz, 1 H, H 3exo or H exo ), 1. (d, J =. Hz, 1 H, H exo or H 3exo ), (m, H), (m, H), 0. (s, 1 H, H 3endo or H endo ), 0. (s, 1 H, H endo or H 3endo ); 13 C MR ( MHz, CDCl 3 ) δ 1., 13.0, 13., 1., 1., 1., 1., 1.,. (C 1 ),. (C ), 3.3 (C 3 or C ), 30. (C or C 3 ),.,.,.,.1,.0,.0 (CH 3 ), 1., 1. (C ); MS (EI) m/z (rel. intensity) 3 (M +, 1), 31 (1), (0), 0 (1), 1 (100); HRMS (EI) calc for C H O S 3.11, found 3.11.

8 H 1 3 e P(O) -(enyl-(3-phenylbicyclo[1.1.0]but-1-yl)methyl)-p,p-diphenylphosphinamide (e). According to the General Protocol C,,-dibromo-1-bromomethyl-phenylcyclopropane 3 (0.30 g, 0.1 mmol) in Et O (.0 ml) was treated with MeLi (0. ml, 0.1 mmol, c = 1. M in Et O), followed by t-buli (0. ml, 0.1 mmol, c = 1. M in pentane) and a solution of CH=P(O) (0.11 g, 0.3 mmol) in THF (.0 ml). The reaction mixture was warmed up to rt, quenched with sat. H Cl and extracted (3x) with EtOAc. The combined organic layers were washed with water, brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded f (0.10 g, 3%) as a colorless oil: IR (neat) 30, 10, 1, 13, 111 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.3 (ddd, J = 10.,., 1. Hz, H),.0 (ddd, J = 1.1,.1, 1. Hz, H),.-.3 (m, H),.31-. (m, H), (m, H),.3 (dd, J =., 1. Hz, H),.1 (dd, J =., 1. Hz, H),. (app t, J =. Hz, 1 H, H 1 ),. (dd, J =.,.3 Hz, 1 H, H),.13 (d, J =. Hz, 1 H, H 3exo or H exo ), 1. (d, J =. Hz, 1 H, H exo or H 3exo ), 0. (s, 1 H, H 3endo or H endo ), 0. (s, 1 H, H endo or H 3endo ); 13 C MR ( MHz, CDCl 3 ) δ 10., 10.3, 13., 13.1, 13.0, 131., 131., 131., 131., 1.3, 1., 1., 1.11, 1.0, 1., 1.1, 1.01, 1., 1.03,.0 (C 1 ), 33.1 (C 3 or C ), 30.1 (C or C 3 ),.30 (d, J =. Hz, C ), 0.1 (C ); MS (EI) m/z (rel. intensity) 3 (M +, 1), 30 (0), 1 (3), 01 (100); HRMS (EI) calc for C H OP 3.1, found 3.1. P(O) H 1 3 f -(,-Dimethyl-1-(3-phenylbicyclo[1.1.0]but-1-yl)propyl)-P,P-diphenylphosphinamide (f). According to the General Protocol C,,-dibromo-1-bromomethyl-phenylcyclopropane 3 (0.30 g, 0.1 mmol) in Et O (.0 ml) was treated with MeLi (0. ml, 0.1 mmol, c = 1. M in Et O), followed by t-buli (0. ml, 0.1 mmol, c = 1. M in pentane) and a solution of t-buch=p(o) (0.03 g, 0.3 mmol) in THF (.0 ml). The reaction mixture was warmed up to rt, quenched with sat. H Cl and extracted (3x) with EtOAc. The combined organic layers were washed with water, brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded f (0.0 g, 1%) as a colorless oil: IR (neat), 13, 11, 113, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.-.1 (m, H),.-.1 (m, 13 H), 3.1 (dd, J = 11.0,. Hz, 1 H, H 1 ),. (dd, J = 11.0,. Hz, 1 H, H),.1 (d, J =. Hz, 1 H, H 3exo or H exo ),.03 (d, J =., 1 H, H exo or H 3exo ), 1.0

9 (s, 10 H, H 3endo or H endo, H ), 0. (s, 1 H, H endo or H 3endo ); 13 C MR ( MHz, CDCl 3 ) δ 13., 13.0, 13., 13.0, 13., 13., 13.1, 131.1, , 131., , 1., 1.3, 1.0, 1.0, 1.03, 1.1, 1., 1.1,. (C 1 ), 3. (C 3 or C ), 33. (C or C 3 ), 30.1 (d, J =. Hz, C ),. (C ),.1 (C ), 1.3 (C ); MS (EI) m/z (rel. intensity) 1 (M +, ), 1 (), 3 (), (11), 1 (100), 11 (), 1 (1); HRMS (EI) calc for C H 30 OP 1.0, found Me 3 1 P(O) (S*,R*,R*)--(-(P,P-Diphenylphosphinyl))--methyl-,-diphenyl--azaspiro[3.]oct-1-ene (). General Protocol D. Bicyclobutane a (0.0 g, 0.11 mmol), allyl bromide (0.0 g, 0. mmol) and Bu HSO (0.00 g, 0.0 mmol) were dissolved in Me (.0 ml), and treated with 0% aq aoh (.0 ml). The reaction mixture was vigorously stirred at rt for 3 h, diluted with water, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The product was purified by chromatography on SiO (hexanes/etoac, 1:) to give (0.033 g, 3%) as a colorless oil: IR (neat), 1, 13, 100, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ. (ddd, J = 11.,., 1. Hz, 3 H),.1 (ddd, J = 11.,.3, 1.3 Hz, 3 H),.-. (m, H),.3-.0 (m, H),.1-.0 (m, H),. (s, 1 H, H 1 ),. (d, J = 11.3 Hz, 1 H, H ), (m, 1 H, H ), (m, 1 H, H ),.1-. (m, 1 H, H ),.3 (d, J = 13. Hz, 1 H, H 3 ),. (d, J = 13. Hz, 1 H, H 3 ), 0. (d, J =. Hz, 3 H, H ); 13 C MR ( MHz, CDCl 3 ) δ 1.0, 1.0, 13.0, 13., 13.3, 13.3, 13.0, 131., 131., 1., 1.3, 1.3, 1., 1., 1., 1., 1., 1., 1.,. (C ),. (d, J = 3. Hz, C ),. (C ), 3. (C ), 3.3 (C 3 ), 11. (C ); MS (EI) m/z (rel. intensity) (M +, ), 31 (), 30 (), (), 30 (0), 01 (100); HRMS (EI) calc for C 3 H 30 OP.0, found.0. MeO C Me 3 1 P(O) (S*,R*,R*)--(-(P,P-Diphenylphosphinyl))--((-methoxycarbonyl)phenyl)--methyl--phenyl-- azaspiro[3.]oct-1-ene (). According to General Protocol D, bicyclobutane a (0.10 g, 0.0 mmol), allyl

10 bromide (0.1 g, 1.0 mmol) and Bu HSO (0.03 g, 0.10 mmol) were dissolved in Me (10.0 ml) and treated with 0% aq aoh (10.0 ml). The reaction mixture was vigorously stirred at rt for 3 h, diluted with water, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The residue was purified by chromatography on SiO (hexanes/etoac, 1:) to afford as a colorless oil (0.00 g, 3%): IR (neat) 30,,, 1, 11, 11, 1, 13, 13, 110, 13, 10, 113, 111, 110 cm -1 ; 1 H MR (00 MHz, CDCl 3 ) δ.0-. (m, H),.3 (dd, J = 11.1,.1 Hz, H),.-. (m, 3 H),.0 (d, J =. Hz, H),.31-. (m, H), (m, H),. (s, 1 H, H 1 ),. (d, J = 11. Hz, 1 H, H ), 3. (s, 3 H, OCH 3 ), 3. (app t, J =.3 Hz, 1 H, H ), 3. (q, J = 10.3 Hz, 1 H, H ),.-. (m, 1 H, H ),. (d, J = 13.3 Hz, 1 H, H 3 ),.30 (d, J = 13.3 Hz, 1 H, H 3 ), 0. (d, J =. Hz, 3 H, H ); 13 C MR ( MHz, CDCl 3 ) δ 1. (CO), 1.03, 13., 13.3, 13.0, 13., 13.3, 13.1, 13.3, 13.0, 131., , 1., 1.1, 1., 1.3, 1., 1., 1., 1., 1.,.3 (C ),.03 (d, J = 3. Hz, C ),. (C ), 1. (OCH 3 ), 3.0 (d, J =. Hz, C ), 3.1 (C 3 ), 11.1 (C ); MS (EI) m/z (rel. intensity) 33 (M +, 1), 33 (), 30 (3), 30 (11), 1 (1), 01 (0), 11 (100); HRMS (EI) calc for C 3 H 3 O 3 P 33.10, found MeO C 10 Me Me 3 1 P(O) (S*,R*)--(-(P,P-Diphenylphosphinyl))--((-methoxycarbonyl)phenyl)-,-dimethyl--phenyl-- azaspiro[3.]oct-1-ene () from c. A mixture of bicyclobutane a (0.030 g, 0.01 mmol), 3-bromo-- methylpropene (0.030 ml, mmol), Bu HSO (0.010 g, mmol), powdered aoh (0.01 g, 0.1 mmol) and K CO 3 (0.0 g, 0.30 mmol) in Me (3.0 ml) was vigorously stirred at rt for. h and at 110 ºC for an additional 1 h. The reaction mixture was diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The residue was purified by chromatography on SiO (hexanes/etoac, 1:) to afford a mixture (.3:1) of diastereoisomers of (0.0 g, %) as a colorless oil. Major isomer: 1 H MR (300 MHz, CDCl 3 ) δ.03-. (m, 3 H),.3-. (m, H), (m, H),.0-. (m, H),.3 (s, 1 H, H 1 ),. (d, J = 11.0 Hz, 1 H, H ), 3. (s, 3 H, OCH 3 ), (m, H, H ),. (d, J = 1. Hz, 1 H, H 3 ),.3 (d, J = 1. Hz, 1 H, H 3 ), 1.3 (s, 3 H, H or H 10 ), 0. (s, 3 H, H 10 or H ); 13 C MR ( MHz, CDCl 3 ) δ 1.0 (CO), 1., 11., 11.30, 133., 13., 13., 13.30, 13.1, 131., 131., 1., 1., 1.3, 1.30, 1.3, 1.3, 1., 1.1, 1.3, 1.,.1 (C ), 0. (C ),. (C ), 1. (OCH 3 ),. (C ), 31.0 (C 3 ), 3.1 (C or C 10 ), 1. (C 10 or C ); IR(neat), 10, 10, 13, 10, 113, 11, 110 cm -1 ; MS (EI) m/z (rel. intensity) (M +, ), 3 (), 00

11 C 10 Me 3 1 P(O) (10), 0 (), 3 (3), 30 (1), 01 (100); HRMS (EI) calc for C 3 H 3 O 3 P., found.1. Minor isomer (representative signals): 1 H MR (300 MHz, CDCl 3 ) δ.0 (s, 1 H, H 1 ),.1 (d, J = 11. Hz, 1 H, H ), 3. (s, 3 H, OCH 3 ), 3.31 (app d, J = 10. Hz, 1 H, H ),.0 (d, J = 13. Hz, 1 H, H 3 ), 1.3 (s, 3 H, H or H 10 ), 1.0 (s, 3 H, H 10 or H ); 13 C MR ( MHz, CDCl 3 ) δ. (C ), 3. (C ), 3. (C 3 ), 3. (C or C 10 ), 1.1 (C 10 or C ),. Synthesis of from -((3-(-methoxycarbonylphenyl)bicyclo[1.1.0]but-1-yl)(phenyl)methyl)--(- methylallyl)-p,p-diphenylphosphinamide (1). A solution of bicyclobutane 1 (0.0 g, 0.0 mmol) in Me (1. ml) was heated at reflux (110 ºC) for. h. The solvent was evaporated, and purification of the residue by chromatography on SiO (hexanes/etoac, 1:) afforded a diastereomeric mixture (.:1) of (0.00 g, 0%). (S*,R*,R*)--(-Cyanophenyl)--(-(P,P-diphenylphosphinyl))--ethyl--phenyl--azaspiro[3.]oct-1- ene (). A suspension of bicyclobutane b (0.11 g, 0. mmol), crotyl bromide (0.1 ml, 1. mmol), Bu HSO (0.01 g, 0.1 mmol), powdered aoh (0.10 g,. mmol) and K CO 3 (0.1 g, 1. mmol) in Me (10 ml) was vigorously stirred at rt for h, and at 0 o C for an additional 1 h. The reaction mixture was diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded (0.03 g, 1%) as a colorless oil: IR (neat) 300, 0,, 3,, 11, 1, 1, 1, 13, 1, 11, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ. (ddd, J = 11.,., 1. Hz, H),.-. (m, H),.0-. (m, H),.3-.3 (m, H), (m, 3 H),.1-.0 (m, H),.00 (s, 1 H, H 1 ),.1 (d, J = 11. Hz, 1 H, H ), 3. (ddd, J = 11.0,.0, 3.0 Hz, 1 H, H ), 3. (td, J = 1.3, 10.0 Hz, 1 H, H ),. (ddd, J = 1., 10., 3. Hz, 1 H, H ),. (d, J = 13. Hz, 1 H, H 3 ),.30 (d, J = 13. Hz, 1 H, H 3 ), (m, 1 H, H ), (m, 1 H, H ), 0. (t, J =. Hz, 3 H, H 10 ); 13 C MR ( MHz, CDCl 3 ) δ 13., 1., 13.00, 13., 133., 13., 13.1, 13.31, 13.0, 131., 131., 131.1, 1., 1., 1., 1., 1., 1., 1.1, 11. (C), 110.,.33 (C ),. (d, J = 3.0 Hz, C ), 1. (C ),.1 (d, J =.3 Hz, C ), 3. (C 3 ), 1. (C ), 13.0 (C 10 ); MS (ES) m/z (rel. intensity) 101 ([M+a] +, 1), 3 ([M+a] +, ), 1 ([M+1] +, 100); HRMS (ES) calc for C 3 H 3 OP (M+H) 1., found

12 MeO C 3 1 P(O) MeO C 3 1 P(O) 10 (S*,R*,)--(-(P,P-Diphenylphosphinyl))--((-methoxycarbonyl)phenyl)--methylene--phenyl-- azaspiro[3.]oct-1-ene (). According to General Protocol D, a solution of bicyclobutane a (0.3 g, 0. mmol), propargyl bromide (0.0 ml, 3.1 mmol, 0% in Me), and Bu HSO (0.11 g, 0.3 mmol) in Me (30 ml) was treated with 0% aq aoh (30 ml). The reaction mixture was vigorously stirred at rt for h, diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The residual oil was purified by chromatography on SiO (hexanes/etoac, 1:) to afford (0. g, %) as a colorless oil: IR (neat) 30,, 11, 103, 13, 10, 11, 1110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ. (d, J =., 1. Hz, H),. (ddd, J = 11.,., 1. Hz, H),.1 (ddd, J = 11.,.3, 1. Hz, H),.-. (m, H),.0-.3 (m, H), (m, 3 H), (m, H),. (s, 1 H, H 1 ),.3 (d, J = 1. Hz, H, H ),. (d, J = 10.3 Hz, 1 H, H ),.3 (ddt, J = 1., 1.1,. Hz, 1 H, H ),.0 (dd, J = 1.3,. Hz, 1 H, H ), 3.1 (s, 3 H, OCH 3 ), 3. (d, J = 1. Hz, 1 H, H 3 ),. (d, J = 1. Hz, 1 H, H 3 ); 13 C MR ( MHz, CDCl 3 ) δ 1.1 (CO), 10., 1.3, 1., 1., 13., 13.3, 13., 13.0, 13.3, 131., 130., 1.3, 1., 1., 1., 1.30, 1.1, 1.0, 1.00, 1.0, 1., 1., 10. (C ),.1 (C ),. (C ),.03 (OCH 3 ), 0.1 (C ),. (C 3 ); MS (EI) m/z (rel. intensity) 31 (M +, ), 1 (), 330 (), 1 (1), 01 (100); HRMS (EI) calc for C 30 H 3 O 3 P 31.13, found (S*,R*,Z)--(-(P,P-Diphenylphosphinyl))--((-methoxycarbonyl)phenyl)--phenyl - phenylmethylene--azaspiro[3.]oct-1-ene (10). According to General Protocol D, a solution of bicyclobutane a (0.00 g, 0.10 mmol), Bu HSO (0.01 g, 0.01 mmol), and 1-phenyl-3-bromopropyne (0.0 g, 0.1 mmol) in Me (.0 ml) was treated with 0% aq aoh (.0 ml). The reaction mixture was vigorously stirred at rt for 3 h, diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The residual oil was purified by chromatography on SiO (hexanes/etoac, 1:) to afford 10 (0.030 g, %) as a colorless oil: IR (neat) 30, 0, 10, 1, 103, 1, 1, 13, 110, 1310, 11, 11, 1111 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.0 (d, J =. Hz, H),. (ddd, J = 11.,., 1. Hz, H),.3 (ddd, J = 11.,.3, 1.3 Hz, H),.-.3 (m, H),.3-.1 (m, 11

13 H),.11 (d, J =. Hz, H),. (dd, J =.,. Hz, H),.33 (s, 1 H, H 1 ),. (s, 1 H, H ),. (ddd, J = 1., 11.1,. Hz, 1 H, H ),. (d, J =. Hz, 1 H, H ),.3 (ddd, J = 1.1,.1, 1. Hz, 1 H, H ), 3. (s, 3 H, OCH 3 ), 3.3 (d, J = 1. Hz, 1 H, H 3 ), 3.0 (d, J = 1. Hz, 1 H, H 3 ); 13 C MR ( MHz, CDCl 3 ) δ 1.3 (CO), 1., 13., 1., 13., 13.3, , 13., 13.3, 131., 131.3, 130., 1., 1., 1.3, 1.1, 1.3, 1.0, 1.0, 1., 1., 1., 11.3,.0 (C ),. (C ),.10 (OCH 3 ),.00 (C ),. (C 3 ); MS (EI) m/z (rel. intensity) 0 (M +, 0), 0 (0), 30 (), 1 (1), 01 (100); HRMS (EI) calc for C H O (M-C 1 H 10 OP) 0.10, found Me Me 1 Si 1 3 O 1 S 11 O Me (S*,R*,Z)--Cyclohexyl--(-tosyl)--phenyl--(triisopropylsilyl)methylene--azaspiro[3.]oct-1-ene (11). According to the General Protocol D, a solution of bicylobutane d (0.0 g, 0.1 mmol), (3-bromoprop-1- ynyl)triisopropylsilane (0. g, 0. mmol) and Bu HSO (0.0 g, 0.0 mmol) in Me (.0 ml) was treated with 0 % aq aoh (.0 ml). The reaction mixture was vigorously stirred at rt for h, diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and concentrated. Purification by chromatography on SiO (hexanes/etoac, :1) afforded 11 (0.0 g, %) as a colorless foam: IR (neat), 1, 1, 13, 11 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.0 (d, J =. Hz, H), (m, H),. (m, H),.1 (s, 1 H, H 1 ),. (app. t, J =.1 Hz, 1 H, H ),. (dd, J = 1.0,.0 Hz, 1 H, H ),.13 (dd, J = 1.0, 1. Hz, 1 H, H ), 3. (d, J = 3. Hz, 1 H, H ),. (s, 3 H, H 1 ), 1. (d, J = 1. Hz, 1 H, H 3 ), 1.3 (d, J = 1. Hz, 1 H, H 3 ), (m, H, H 10, H 11, H 1, H 1 or H 1 ), (m, H, H 1 or H 1, H 13, H 1, H 1 ); 13 C MR ( MHz, CDCl 3 ) δ 11.0, 1., 13., 13.1, 133., 1., 1., 1., 1.3, 1., 11., 1.1 (C ),. (C ),. (C ),.3 (C 3 ), 3. (C 10 ), 31.1,.,. (x),., 1. (C 1 ), 1.0 (C 1 or C 1 ), 1. (C 1 or C 1 ), 11. (C 1 ); MS (EI) m/z (rel. intensity) (M +, 30), 0 (100), 3 (1); HRMS (EI) calc for C 3 H 1 O SSi.310, found.33. 1

14 H endo H exo 1 (O)P H exo H endo CO Me 1 (S*,R*,S*)-3-(-(P,P-Diphenylphosphinyl))--((-methoxycarbonyl)phenyl)-,-diphenyl-3- azatricyclo[ , ]nonane (1) from (E)-cinnamyl bromide. According to General Protocol C, a solution of bicyclobutane 1a (0.030 g, 0.01 mmol), (E)-cinnamyl bromide (0.0 g, 0.30 mmol) and Bu HSO (0.010 g, mmol) in Me (3.0 ml) was treated with 0% aq aoh (3.0 ml). The reaction mixture was vigorously stirred at rt for h, diluted with water, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded 1 (0.03 g, 3%) as a colorless oil: IR (neat) 30, 30,, 10, 111, 1, 11, 13, 1310, 10, 11, 1111 cm -1 ; 1 H MR (00 MHz, CDCl 3 ) δ. (dd, J = 10.,. Hz, H),. (d, J =. Hz, H),. (dd, J = 11.,. Hz, H),.0-.3 (m, 3 H),.1 (t, J =. Hz, 3 H),.1 (d, J =.0 Hz, 1 H),.11 (dd, J =.,. Hz, H),.-. (m, 3 H),.1 (d, J =. Hz, H),.1 (s, H),.0 (d, J =. Hz, 1 H, H ), 3. (s, 3 H, OCH 3 ), 3. (t, J =. Hz, 1 H, H ), 3.3 (q, J =. Hz, 1 H, H ), 3.3 (d, J =.1 Hz, 1 H, H ),. (bs, 1 H, H ),. (dd, J =.3,. Hz, 1 H, H endo ), 1. (d, J =. Hz, 1 H, H exo ), 1.0 (d, J =. Hz, 1 H H exo ), 1. (dd, J =.,. Hz, 1 H, H endo ); 13 C MR ( MHz, CDCl 3 ) δ 1.1 (CO), 1., 11.0, 11., 10.3, 13.0, 13., 13.0, 13., 131.0, 1.1, 1., 1.0, 1., 1.3, 1.1, 1.0, 1., 1., 1., 1.0,. (C ),.0 (C ),. (d, J =. Hz, C 1 ),.1 (C ),.0 (OCH 3 ), 1.3 (d, J =.0 Hz, C ),. (C ),. (C ), 3. (C ); MS (EI) m/z (rel. intensity) 0 (M +, 1), 3 (3), 0 (33), 3 (1), 333 (1), 30 (1), 30 (), 30 (1), 01 (100); HRMS (EI) calc for C 0 H 3 O 3 P 0.33, found 0.3. The relative configuration of 1 was assigned based on OESY experiment, showing following noe enhancements (copy of OESY spectra of 1 is given at the end of Supporting Material): H H H H R H H H 1, R = p-c H CO Me P(O) Synthesis of 1 from (Z)-cinnamyl bromide. According to General Protocol C, a solution of bicyclobutane a (0.03 g, 0.03 mmol), freshly prepared (Z)-cinnamyl bromide (0.01 g, 0.3 mmol) and Bu HSO, (0.01 g, 0.03 mmol) in Me (3.0 ml) and 0% aq aoh (3.0 ml) was vigorously stirred at rt for 13

15 1 h. The reaction mixture was diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification of the residue by chromatography on SiO (hexanes/etoac, 1:) afforded 1 (0.03 g, %). 1 P(O) 13 (S*,R*,S*)-3-(-(P,P-Diphenylphosphinyl))-,-diphenyl--(pyridin-3-yl)-3-azatricyclo[ , ]nonane (13). According to General Protocol C, a solution of bicyclobutane c (0.01 g, 0.1 mmol), (E)-cinnamyl bromide (0.01 g, 0. mmol) and Bu HSO (0.00 g, 0.0 mmol) in Me (.0 ml) and 0 % aq aoh (.0 ml) was vigorously stirred at rt for 1 h, diluted with water, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification of the residue by chromatography on SiO (hexanes/etoac/meoh, 1::1) afforded 13 (0.01 g, 3%) as a colorless oil: IR (neat) 30, 30,, 0, 101, 1, 11, 11, 13, 11, 130, 1300, 1, 13, 11, 111 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ. (bs, 1 H),.03 (bs 1 H),.3-. (m, H),.-.0 (m, H), (m, 3 H),.-.1 (m, H), (m, H),.-.0 (m, H),. (dd, J =.1, 3.1 Hz, H),.1 (d, J =. Hz, 1 H, H ), 3. (app t, J =. Hz, 1 H, H ), 3.3 (q, J =. Hz, 1 H, H ), 3.1 (d, J =.0 Hz, 1 H, H ),. (bs, 1 H, H ),. (t, J =.0 Hz, 1 H, H endo ), 1. (d, J =. Hz, 1 H H exo ), 1.0 (d, J =.0 Hz, 1 H, H exo ), 1.0 (t, J =.1 Hz, 1 H, H endo ); 13 C MR ( MHz, CDCl 3 ) δ 1., 1., 11.3, 10., 133., 13., 13.3, 13., 13.1, 131., 131., 1.1, 1., 1.30, 1.1, 1.0, 1., 1., 1.3, 1., 1., 1.,.3 (C ),. (d, J =. Hz, C 1 ),.1,. (C ),.03 (C ), 1.3 (d, J =. Hz, C ),.0 (C ),.33 (C ), 3.1 (C ); MS (EI) m/z (rel. intensity) (M +, 31), 1 (), 3 (), 31 (), 30 (1), 3 (), 01 (1), 1 (100); HRMS (EI) calc for C 3 H 33 OP.331, found.30. 1

16 1 F 3 C O S O Me (R*,R*,S*)-3-(-Tosyl)--cyclohexyl--phenyl--(-trifluoromethylphenyl)-3- azatricyclo[ , ]nonane (1). According to the General Protocol D, bicyclobutane e (0.03 g, 0.0 mmol), (E)-1-(3-bromoprop-1-enyl)--(trifluoromethyl)benzene (0.0.0 g, 0. mol) and Bu HSO (0.01 g, 0.0 mmol) were dissolved in Me (.0 ml) and treated with 0% aq aoh (.0 ml). The reaction mixture was vigorously stirred at rt for h, diluted with water, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac 1:) afforded 1 (0.0 g, %) as a colorless oil: IR (neat),, 11, 13, 11 cm -1 ; 1 H MR (300 MHz, C D ) δ. (d, J =.0 Hz, H),.-.1 (m, H),.-- (m, H),. (d, J =.0 Hz, H),.1-. (m, H), 3. (t, J =.0 Hz, 1 H, H ), 3. (d, J =. Hz, 1 H, H ), 3.0 (t, J =. Hz, 1 H, H ),.1 (d, J =.0 Hz, 1 H, H ),.-.3 (m, 1 H, H ),.1-1. (m, H, H, H ), 1. (s, 3 H, CH 3 ), (m, H, H 10, H 11, H 1, H 13 ), (m, H, H 1, H 1 ); 13 C MR ( MHz, C D ) δ 1., 13.0, 10., 13., 130., 1., 1., 1., 1., 1., 1., 1.,. (C ),. (C ),., 3.,., 1.1,.1,., 0., 30., 30.0,.0,., 1.1; MS (EI) m/z (rel. intensity) (M +, ), (100), (); HRMS (EI) calc for C 3 H 3 O FS.1, found.1. 1 P(O) 1 (S*,R*,S*)-3-(-(P,P-Diphenylphosphinyl))-,,-triphenyl-3-azatricyclo[ , ]nonane (1). According to the General Protocol D, bicyclobutane e (0.03 g, 0.0 mmol), (E)-cinnamyl bromide (0.0.0 g, 0. mol), Bu HSO (0.01 g, 0.0 mmol) were dissolved in Me (.0 ml) and treated with 0% aq aoh (.0 ml). The reaction mixture was vigorously stirred at rt for h, diluted with water, and extracted (3x) with 1

17 EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac 1:) afforded 1 (0.0 g, %) as a colorless oil: IR (neat) 101, 1, 13, 10, 110, 1111 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.0-. (m, H),.1-. (m, H),.-. (m, H),.3-. (m, H),.1-.0 (m, H),.0-. (m, H),.3 (d, J =. Hz, 1 H, H ), 3. (app. t, J =. Hz, 1 H, H ), 3.1 (app. q, J =. Hz, 1 H, H ), 3.3 (bs, 1 H, H ), 3.0 (bs, 1 H, H ),. (dd, J =.,. Hz, 1 H, H endo ), 1. (d, J =.3 Hz, 1 H, H exo ), 1. (d, J =. Hz, 1 H, H exo ), 1. (dd, J =.,.0 Hz, 1 H, H endo ); 13 C MR ( MHz, CDCl 3 ) δ 11.1, 11., 11., 11.0, 13.3, 13.31, 13., 13.1, 131.0, 1., 1.3, 1., 1., 1., 1., 1., 1.0, 1., 1.,.0 (C ),. (C ),.1 (d, J =.3 Hz, C 1 ), 3. (C ), 1.30 (d, J =. Hz, C ),.0 (C ),. (C ), 3. (C ); MS (EI) m/z (rel. intensity) 1 (M +, ), 3 (), 30 (30), 30 (), 30 (), 01 (100); HRMS (EI) calc for C 3 H 3 OP 1.3, found P(O) 1 (R*,R*,S*)-3-(-(P,P-Diphenylphosphinyl))--tert-butyl-,-diphenyl-3-azatricyclo[ , ]nonane (1). Bicyclobutane f (0.0 g, 0.0 mmol), (E)-cinnamyl bromide (0.0 g, 0.3 mmol) and Bu HSO (0.01 g, 0.03 mmol) were dissolved in Me (3.0 ml), followed by addition of 0% aq aoh (3.0 ml). The reaction mixture was stirred at rt for h, diluted with water, extracted (3x) with EtOAc and the combined organic layers were washed with water, brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexane/etoac, 1:) afforded 1 (0.01 g, %) as a colorless oil: IR (neat) 1, 13, 101, 111, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.-. (m, H),.-. (m, H),.1-.0 (m, H),.-.3 (m, H),.-. (m, H), 3.1 (d, J =. Hz, 1 H, H ), (m, 1 H, H ), (m, 1 H, H ), 3.0 (d, J =.1 Hz, 1 H, H ), (m, 1 H, H ),. (dd, J =.3,. Hz, 1 H, H endo ),. (d, J =. Hz, 1 H, H exo ), 1.1 (dd, J =.,. Hz, 1 H, H endo ), 1.0 (d, J =. Hz, 1 H, H exo ), 0. (s, H, H 11 ); 13 C MR ( MHz, CDCl 3 ) δ 11.1, 11., 133.3, 13.0, 13., 13.3, 13.1, 131.1, 1.31, 1., 1., 1.1, 1.0, 1., 1.3, 1.0, 1.0, 1., 1.0,. (C ),.3 (C ),.3 (d, J =.3 Hz, C 1 ),.0 (C ), 3.0 (d, J =. Hz, C ), 1.0 (C ), 0.11 (C ), 1.1 (C ), 3. (C 10 ),.1 (C 11 ); MS (EI) (), 0 (3), 01 (100); HRMS (EI) calc for C 3 H OP (M-C H ).1, found

18 O P 3 1 CO Me -((3-(-Methoxycarbonylphenyl)bicyclo[1.1.0]but-1-yl)(phenyl)methyl)--(3-cyclopropylallyl)-P,Pdiphenylphosphinamide (1). According to General Protocol C, a solution of bicyclobutane a (0.0 g, 0.1 mmol), freshly prepared cyclopropylallyl bromide (0.130 g, 0. mmol) and Bu HSO (0.0 g, 0.00 mmol) in Me (.0 ml) was treated with 0% aq aoh (.0 ml), and vigorously stirred at rt for 1 h. The reaction mixture was diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The resulting oil was purified by chromatography on a short pad of SiO (hexanes/etoac, 1:) to afford crude, unstable amide 1 (0.0 g, %): 1 H MR (300 MHz, CDCl 3 ) δ.0-.3 (m, H),.-. (m, H),.-.3 (m, 3 H),.-. (m, 3 H),.3 (dd, J = 1.,. Hz, 1 H, H 1 ),. (dd, J = 1.,. Hz, 1 H, H ),.1 (d, J =.0 Hz, 1 H, H ),.0 (s, 3 H, OCH 3 ), (m, 1 H, H ), (m, 1 H, H ),. (d, J =. Hz, 1 H, H 3exo or H exo ), 1. (d, J =. Hz, 1 H, H exo or H 3exo ), 1.00 (s, 1 H, H 3endo or H endo ), (m, H, H 10, H 11 ), 0. (s, 1 H, H endo or H 3endo ), (m, 1 H, H ); 13 C MR ( MHz, C D ) δ 1. (CO), 1., 13., 13., 13.1, , 13., 13.1, 13., 131.0, 1., 1., 1.3, 1.1, 1.00, 1., 1.1, 1., 1., 1.1,.0 (C 1 ), 1.0 (OCH 3 ),. (C ), 3.0 (C 1 or C ), 3.0 (C or C 3 ),. (d, J = 3. Hz, C 1 ), 3. (C ), 13. (C ),.0 (C 10 or C 11 ),. (C 11 or C 10 ). MeO C P(O) 1a P(O) 1b CO Me (S*,R*,R*)--Cyclopropyl--(-(P,P-diphenylphosphinamido))--((-methoxycarbonyl)phenyl)-- phenyl--azaspiro[3.]oct-1-ene (1a) and (S*,R*,R*)--Cyclopropyl-3-(-(P,Pdiphenylphosphinamido))--((-methoxycarbonyl)phenyl)--phenyl-3-azatricyclo[ , ]nonane (1b). A solution of amide 1 (0.0 g, 0.0 mmol) in Me (.0 ml) was stirred at rt for 1 h. The solvent was removed in vacuo and the residual oil was purified by chromatography on SiO (hexanes/etoac, 1:) to afford 1a (0.01 g, 33%) and 1b (0.01 g, 31%). 1

19 1a. Obtained as a colorless oil: IR (neat) 1, 10, 10, 13, 1, 11, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.-.1 (m, 3 H),.-. (m, H),.1-. (m, H),.3-.3 (m, H),.1-.0 (m, H),. (s, 1 H, H 1 ),.1 (d, J = 11.3 Hz, 1 H, H ), 3.1 (s, 3 H, OCH 3 ), (m, 1 H, H ), 3.33 (app q, J = 10.1 Hz, 1 H, H ),.-.1 (m, 1 H, H ),. (d, J = 13. Hz, 1 H, H 3 ),.30 (d, J = 13. Hz, 1 H, H 3 ), (m, H H ), (m, 1 H, H 10 ), (m, H, H 11 or H 1 ), (m, H, H 1 or H 11 ); 13 C MR ( MHz, CDCl 3 ) δ 1.1 (CO), 13., 13., 13.0, 13.0, 13.1, 133.1, 13.3, 13.0, 13., 13.1, 131., 131., 130., 1., 1.10, 1.0, 1.3, 1., 1., 1.30, 1., 1.,. (C ),. (d, J = 3.3 Hz, C ),.0 (OCH 3 ), 1.1 (C ),. (d, J =. Hz, C ), 33. (C 3 ), 3. (C ),. (C 10 ),. (C 11 or C 1 ),. (C 1 or C 11 ); MS (EI) m/z (rel. intensity) 3 (M +, ), (), 3 (3), 31 (1), 30 (), 30 (31), 1 (), 01 (100); HRMS (EI) calc for C 3 H 3 O 3 P 3.33, found b. Obtained as a colorless oil: IR (neat), 11, 110, 13, 1, 11 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.03-. (m, H),.-.1 (m, H),.-. (m, 3 H), (m, 1 H),.0 (d, J =. Hz, 1 H, H ), 3.0 (s, 3 H, OCH 3 ), 3. (td, J =.,.0 Hz, 1 H, H ), 3. (app q, J = 10.0 Hz, 1 H, H ),.3-. (m, 1 H, H ),. (dd, J =.,. Hz, 1 H, H endo ), 1. (dd, J =., 1. Hz, 1 H, H exo ), 1. (d, J =. Hz, H exo ), 1. (dd, J =.,. Hz, 1 H, H endo ), 1. (dd, J =., 3. Hz, 1 H, H ), (m, 1 H, H 10 ), (m, 1 H, H 11 or H 1 ), (m, 1 H, H 1 or H 11 ), (m, 1 H, H 11 or H 1 ), (m, 1 H, H 1 or H 11 ); 13 C MR ( MHz, CDCl 3 ) δ 1.1 (CO), 1.3, 11.0, 11., 133., 13., 13.3, 13., 13.1, 131., 130., 1., 1., 1.0, 1.0, 1., 1., 1.1, 1., 1.1, 1.,. (C ),. (d, J =. Hz, C 1 ),.1 (C ),.3 (C ), 1. (OCH 3 ), 0. (C ),.1 (C ),. (C ), 3. (C ), 1. (C 10 ),.3 (C 11 or C 1 ),.0 (C 1 or C 11 ); MS (EI) m/z (rel. intensity) 3 (M +, ), 3 (), 3 (3), 30 (), 30 (1), 1 (), 01 (100); HRMS (EI) calc for C 3 H 3 O 3 P 3.33, found 3.3 H O P H -(1-enylprop--ynyl)-P,P-diphenylphosphinamide (0). A solution of -benzylidene-p,pdiphenylphosphinamide (1 g, 3 mmol) in dry THF (100 ml) was cooled to 0 o C and treated with HCCMgBr (10 ml, mmol, 0. M in THF). The reaction mixture was stirred at 0 o C for 30 min, slowly quenched with sat. H Cl, and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. The resulting solid was purified by chromatography on SiO (hexanes/etoac, 1:) to afford 0 (1 g, 0%) as a colorless solid: Mp o C (hexanes/ch Cl ); IR (KBr) 3, 31, 30, 1

20 1 O P 3 1 CO Me, 1, 11, 1, 13, 11, 11, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.1-.0 (m, H),.-. (m, H),.-. (m, H),.-.3 (m, H),. (td J = 10.1,. Hz, 1 H, H 1 ), 3.1 (app t, J =. Hz, 1 H, H),. (d, J =. Hz, 1 H, H 3 ); 13 C MR ( MHz, CDCl 3 ) δ 13., 13., , 13.0, 13., 13., 13.30, 13., 13.1, 13.0, 131.0, , 1.0, 1., 1., 1.1, 1., 3.3 (d, J =.0 Hz, C ), 3. (C 3 ),. (C 1 ); MS (EI) 331 (M +, 3), 30 (0), (), (1), 01 (100), 13 (1), 1 (1), 130 (); HRMS (EI) calc for C 1 H 1 OP , found ((3-(-Methoxycarbonylphenyl)bicyclo[1.1.0]but-1-yl)(phenyl)methyl)--(-methylallyl)-P,Pdiphenylphosphinamide (1). According to General Protocol C, a solution of bicyclobutane a (0.10 g, 0.0 mmol), 3-bromo--methylpropene (0.10 ml, 1.0 mmol) and Bu HSO (0.013 g, 0.10 mmol) in Me (10 ml) and 0% aq aoh (10 ml) was vigorously stirred at rt for 1 h. The reaction mixture was diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ), and evaporated. Purification by chromatography on SiO (hexanes/etoac, 1:) afforded 1 (0.10 g, 0%) as a colorless oil: IR (neat) 30,, 11, 10, 13, 1311, 10, 111, 111 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.-. (m, H),. (d, J =.3 Hz, H),.3-. (m, 3 H),.10 (d, J =. Hz, H),.01 (t, J =. Hz, H),. (d, J =. Hz, H),.3 (d, J =. Hz, H),. (d, J =. Hz, H, H ),.3 (d, J = 11. Hz, 1 H, H 1 ), 3. (s, 3 H, OCH 3 ), 3.3 (dd, J = 1.1, 10. Hz, 1 H, H ), 3. (dd, J = 1.3, 10. Hz, 1 H, H ),. (d, J =.0 Hz, 1 H, H 3exo or H exo ), 1. (d, J =.3 Hz, 1 H, H exo or H 3exo ), 1. (s, 3 H, H ), 0. (s, 1 H, H 3endo or H endo ), 0.1 (s, 1 H, H endo or H 3endo ); 13 C MR (. MHz, CDCl 3 ) δ 1.3 (CO), 1.0, 11., 11., 13.1, 13.1, 13., 133., 13.1, 13., 13., 13.30, 1.1, 1., 1.3, 1.1, 1., 1.3, 1., 1., 113. (C ), 3.10 (C 1 ), 3.1 (C ),.0 (OCH 3 ), 3. (C 3 or C ), 3.31 (C or C 3 ),. (d, J =. Hz, C ), 3.1 (C ), 0.0 (C ); MS (EI) m/z (rel. intensity) (M +, 1), 3 (), 31 (1), 30 (10), (), 30 (3), 1 (1), 01 (), 13 (), 11 (100); HRMS (EI) calc for C 3 H 3 O 3 P., found P(O) 1

21 -Cinnamyl--(3-phenylprop--ynyl)-P,P-diphenylphosphinamide (). To a solution of -(3-phenylprop-- ynyl)--diphenylphosphinamide (0.00 g, 0.1 mmol) in Me (.0 ml) was added freshly prepared (Z)- cinnamyl bromide (0.1 g, 0. mmol) followed by Bu HSO (0.0 g, 0.0 mmol) and 0% aq aoh (.0 ml). The reaction mixture was vigorously stirred at rt for 1 h, diluted with water and extracted (3x) with EtOAc. The combined organic layers were washed with water and brine, dried (a SO ) and evaporated. The crude oil was purified by chromatography on SiO (hexanes/etoac, 1:) to afford 1 (0.0 g, %) as a colorless oil: IR (neat) 30, 1, 10, 13, 13, 103, 11, 110 cm -1 ; 1 H MR (300 MHz, CDCl 3 ) δ.00 (dd, J =.,. Hz, H),.1-.1 (m, H),.0-. (m, H),. (d, J = 11. Hz, 1 H, H ),. (td, J = 1.1,. Hz, 1 H, H ),.1 (dd, J =.0,. Hz, H, H 1 ),.0 (d, J =. Hz, H, H ); 13 C MR ( MHz, CDCl 3 ) δ 13.30, 13., 13., 13.31, 13.11, 131., 131.3, 131., 130.0, 1., 1., 1., 1.1, 1.10, 1.0, 1.03, 1., 1.,.0 (d, J =. Hz, C ),.3 (C 3 ), 3.3 (d, J = 3.0 Hz, C ), 3.30 (d, J =.3 Hz, C 1 ); MS (EI) m/z (rel. intensity) (M +, 1), (), 33 (), (1), 30 (10), 1 (), 10 (100); HRMS (EI) calc for C 30 H OP (M-H).1, found.11. References: 1. M. Banerjee, S. Roy, Org. Lett. 00,, S. C. Ward, S. A. Fleming, J. Org. Chem. 1,, A. B. Charette, C. Molinaro, C. Brochu, J. Am. Chem. Soc. 001, 13, A. Al-Dulayymi, Z. Li, M. euenschwander, Helv. Chem. Acta 000, 3, 1-.. W. B. Jennings, C. J. Lovely, Tetrahedron 11,, 1-.. A. A. Cantrill, A.. Jarvis, H. M. I. Osborn, J. B. Sweeney, Synlett 1, -.. F. Chemla, V. Hebbe, J.-F. ormant, Synthesis 000, -.. Prepared by the reaction of P(O)Cl with propargyl amine, followed by Sonogashira coupling with iodobenzene. 0

22 OESY spectrum of cpd 1 1