Diastereoselective Ring-Closing Metathesis
CH2CHdCH2), 21.8 ppm (d, 3J(C,P) 3.0 Hz, CH3); 31P NMR (101
MHz, CDCl3) δ 28.5 ppm; IR (film) ν 1643 and 1608 (CdC),
1215 (PdO); HRMS (CI) m/z calcd for C9H16O2P [M + H]+
187.0888, found 187.0890.
General Procedure for the RCM of Phosphinates 1.
To a 0.02 M solution of a phosphinate 1 in dichloromethane
was added catalyst 3 (2 mol %). The mixture was stirred at
reflux for 30 min and then concentrated in vacuo.
phosphinate 5 (1 equiv) in dichloromethane were added
styrene (3 equiv) and catalyst 3 (2 mol %). The mixture was
stirred at reflux. Further portions of catalyst (2 mol %) were
added at 12 h intervals, and further portions of styrene (3
equiv) were added at 24 h intervals. Upon completion of the
reaction or after stirring for 48 h, the solution was concen-
trated in vacuo.
Cross-Metathesis of 5a with Styrene. Cyclic phosphinate
5a (4:1 mixture of cis and trans diastereomers) (49 mg, 0.31
mmol) underwent cross-metathesis with styrene (100 µL, 0.93
mmol) in the presence of catalyst 3 (10 mg, 0.012 mmol, 4 mol
%) as described in the general procedure above. After 24 h,
1H NMR showed that complete conversion of both diastereo-
mers of 5a had occurred. Purification by flash chromatography
(EtOAc to EtOAc/MeOH 98:2) afforded the cis and trans
diastereomers of 6a as white solids, which were recrystallized
from toluene. (2RS,6SR)-6-Methyl-2-(E)-styryl 5,6-dihydro-
1,2-oxaphosphorin 2-oxide cis-6a: yield 45 mg (61%); Rf 0.3
(EtOAc/MeOH 95:5); mp 126-130 °C; 1H NMR (400 MHz,
RCM of 1a. Phosphinate 1a (151 mg, 0.81 mmol) underwent
RCM according to the general procedure above to form cyclic
phosphinate 5a in 60% de. Purification by flash chromatog-
raphy (EtOAc/MeOH 98:2 to EtOAc/MeOH 95:5) afforded 5a
as a brown oil. The diastereomers were not separated. 6-Meth-
yl-2-vinyl-5,6-dihydro-1,2-oxaphosphorin 2-oxide 5a: yield
132 mg (100%); Rf 0.3 (EtOAc/MeOH 9:1); 1H NMR (400 MHz,
CDCl3) δ 6.83 (dddd, 3J(H,P) 37.9, 3J(H,H) 12.7, 3J(H,H) 5.5, 3J(H,H)
2.6 Hz, 1H; PCHdCH)trans, 6.77 (dddd, 3J(H,P) 39.0, 3J(H,H) 12.6,
3
3J(H,H) 5.5, J(H,H) 2.4 Hz, 1H; PCHdCH), 6.38 (m, 1H; PCHd
CHcisHtrans), 5.96-6.29 (m, 3H; PCH)CHcisHtrans and PCH)CH),
4.72 (m, 1H; POCH), 4.46 (m, 1H; POCH)trans, 2.32-2.46 (m,
2H; PCHdCHCH2)trans, 2.29 (m, 2H; PCHdCHCH2), 1.42 (d,
3J(H,H) 6.1 Hz, 3H; CH3)trans, 1.41 ppm (dd, 3J(H,H) 6.1, 4J(H,P) 1.2
3
3
CDCl3) δ 7.57 (dd, J(H,P) 21.5, J(H,H) 17.5, 1H; PCHdCHPh),
7.47-7.49 (m, 2H, Ar-H), 7.34-7.38 (m, 3H, Ar-H), 6.76
3
3
3
(dddd, J(H,P) 39.2, J(H,H) 12.5, J(H,H) 4.0 Hz × 2, 1H; PCHd
2
Hz, 3H; CH3); 13C NMR (101 MHz, CDCl3): δ 146.0 (d, J(C,P)
2
3
CHCH2), 6.25 (dd, J(H,P) 20.6, J(H,H) 17.5 Hz, 1H; PCHd
CHPh), 6.06 (dd, J(H,P) 24.0, J(H,H) 12.7 Hz, 1H; PCHd
2
1.0 Hz, PCHdCH), 136.3 (d, J(C,P) 2.0 Hz, PCHdCH2), 129.0
2
3
(d, 1J(C,P) 139.8 Hz, PCHdCH2), 120.4 (d, 1J(C,P) 119.8 Hz, PCHd
3
CHCH2), 4.81 (ddq, J(H,H) 6.2 Hz × 3, 1H; POCH), 2.26 (m,
2
3
CH), 69.8 (d, J(C,P) 6.0 POCH), 34.5 (d, J(C,P) 8.9 Hz, PCHd
CHCH2), 22.0 ppm (d, 3J(C,P) 7.6 Hz, CH3); 31P NMR (101 MHz,
CDCl3) δ 25.5 (trans), 22.2 ppm (cis); IR (film) ν 1612 (CdC),
1217 (PdO); HRMS (CI) m/z calcd for C7H12O2P [M + H]+
159.0575, found 159.0571.
2H; PCHdCHCH2), 1.41 ppm (d, 3J(H,H) 6.2 Hz, 3H; POCHCH3);
13C NMR (101 MHz, CDCl3) δ 149.4 (d, J(C,P) 6.3 Hz, PCHd
2
CHPh), 145.3 (s, PCHdCHCH2), 134.9 (d, 3J(C,P) 20.8 Ar-Cipso),
130.2 (s, Ar-Cpara), 128.7 (s, Ar-C), 127.7 (s, Ar-C), 121.0 (d,
1J(C,P) 121.3 Hz, PCHdCHCH2), 116.9 (d, J(C,P) 146.9 Hz,
1
RCM of 1b. Phosphinate 1b (145 mg, 0.55 mmol) under-
went RCM according to the general procedure above to form
cyclic phosphinate 5b in 19% de. Purification by flash chro-
matography (EtOAc/MeOH 98:2 to EtOAc/MeOH 95:5) af-
forded the cis and trans diastereomers of 5b as brown oils.
(2SR,5SR)-5-Benzyl-2-vinyl-5,6-dihydro-1,2-oxaphospho-
rin 2-oxide cis-5b: yield 59 mg (45%); Rf 0.1 (EtOAc); 1H NMR
(400 MHz, CDCl3) δ 7.14-7.34 (m, 5H; Ar-H), 6.83 (ddd, 3J(H,P)
37.8, 3J(H,H) 12.6, 3J(H,H) 5.2 Hz, 1H; PCHdCH), 6.06-6.42 (m,
3H; PCHdCH2), 6.03 (dd, 2J(H,P) 22.9, 3J(H,H) 12.6 Hz, 1H; PCHd
PCHdCHPh), 69.8 (d, 2J(C,P) 6.1 POCH), 34.5 (d, 3J(C,P) 8.8 Hz,
PCHdCHCH2), 22.0 ppm (d, J(C,P) 7.6 Hz, POCHCH3); 31P
3
NMR (101 MHz, CDCl3) δ 22.5 ppm; IR (film) ν 1608 (CdC),
1205 (PdO); HRMS (CI) m/z calcd for C13H16O2P [M + H]+
235.0888, found 235.0894. (2RS,6RS)-6-Methyl-2-(E)-styryl-
5,6-dihydro-1,2-oxaphosphorin 2-oxide trans-6a: yield 12
mg (16%); Rf 0.4 (EtOAc/MeOH 95:5); mp 126-130 °C; 1H
NMR (400 MHz, CDCl3) δ 7.33-7.52 (m, 6H, Ar-H and PCHd
3
3
3
3
CHPh), 6.85 (dddd, J(H,P) 38.1, J(H,H) 12.6, J(H,H) 2.6, J(H,H)
2
3
1.0 Hz, 1H; PCHdCHCH2), 6.46 (dd, J(H,P) 27.8, J(H,H) 17.8
2
3
3
CH), 4.49 (ddd, J(H,H) 11.6, J(H,P) 8.6, J(H,H) 3.3 Hz, 1H;
2
3
Hz, 1H; PCHdCHPh), 6.09 (ddm, J(H,P) 21.1, J(H,H) 12.6 Hz,
1H; PCHdCHCH2), 4.57 (m, 1H; POCH), 2.40-2.49 (m, 1H;
PCHdCHCHAHB), 2.30-2.37 (m, 1H; PCHdCHCHAHB) 1.45
3
2
POCHAHB), 4.07 (ddm, J(H,P) 17.2, J(H,H) 11.6 Hz, 1H;
POCHAHB), 2.83 (dd, J(H,H) 13.5, J(H,H) 6.5 Hz, 1H; CHAHB-
2
3
2
3
Ph), 2.72 (dd, J(H,H) 13.5, J(H,H) 8.8 Hz, 1H; CHAHBPh), 2.59
ppm (m, 1H; CHCH2Ph ); 13C NMR (101 MHz, CDCl3): δ 150.3
(s, PCHdCH), 138.0 (s, Ar-Cipso), 136.3 (d, 2J(C,P) 2.7 Hz, PCHd
ppm (d, J(H,H) 6.3 Hz, 3H; POCHCH3); 13C NMR (101 MHz,
3
CDCl3) δ 147.3 (d, 2J(C,P) 6.8 Hz, PCHdCHPh), 146.8 (s, PCHd
3
CHCH2), 134.9 (d, J(C,P) 20.1 Ar-Cipso), 130.2 (s, Ar-Cpara),
1
CH2), 129.0 (s, Ar-C), 128.9 (d, J(C,P) 138.3 Hz, PCHdCH2),
1
128.8 (s, Ar-C), 127.7 (s, Ar-C), 120.4 (d, J(C,P) 119.7 Hz,
128.7 (s, Ar-C), 126.8 (s, Ar-Cpara), 120.0 (d, 1J(C,P) 119.3 Hz,
1
PCHdCHCH2), 118.1 (d, J(C,P) 135.9 Hz, PCHdCHPh), 73.3
2
3
PCHdCH), 65.5 (d, J(C,P) 6.3 POCH2), 38.6 (d, J(C,P) 9.2 Hz,
CHCH2Ph), 37.1 ppm (d, 4J(C,P) 2.3 Hz, CH2Ph); 31P NMR (101
MHz, CDCl3) δ 20.5 ppm; IR (film) ν 1604 (CdC), 1219
(PdO); HRMS (CI) m/z calcd for C13H16O2P [M + H]+ 235.0888,
found 235.0900. (2SR,5RS)-5-Benzyl-2-vinyl-5,6-dihydro-
1,2-oxaphosphorin 2-oxide trans-5b: yield 42 mg (33%); Rf
2
3
(d, J(C,P) 7.1 POCH), 34.0 (d, J(C,P) 10.9 Hz, PCHdCHCH2),
22.1 ppm (d, J(C,P) 7.1 Hz, POCHCH3); 31P NMR (101 MHz,
3
CDCl3) δ 24.8 ppm; IR (film) ν 1610 (CdC), 1209 (PdO); HRMS
(CI) m/z calcd for C13H16O2P [M + H]+ 235.0888, found
235.0890.
1
0.2 (EtOAc); H NMR (400 MHz, CDCl3) δ 7.17-7.34 (m, 5H;
3
3
4
Ar-H), 6.71 (dddd, J(H,P) 37.8, J(H,H) 12.6, J(H,H) 1.2 Hz × 2,
Acknowledgment. We sincerely thank Rhodia Or-
ganique Fine and the EPSRC (GR/N34901/01(P)) for
generous financial support to K.S.D. and F.B., respec-
tively. We also thank Dr. Tim Claridge (Chemistry
Research Laboratory, Oxford) and Jean-Pierre Corbet
(Rhodia Organique Fine) for helpful discussions and Dr.
Andrew Cowley for performing the X-ray crystallogra-
phy analysis (Chemistry Research Laboratory, Oxford).
3
3
2
1H; PCHdCH), 6.34 (ddd, J(H,P) 24.2, J(H,H) 17.7, J(H,H) 2.6
Hz, PCHdCHcisHtrans), 6.07-6.27 (m, 2H; PCHdCHcisHtrans),
2
3
4
6.02 (ddd, J(H,P) 23.3, J(H,H) 12.7, J(H,H) 2.3 Hz, 1H; PCHd
CH), 4.12-4.26 (m, 2H; POCH2), 2.82 (m, 1H; CHCH2Ph), 2.72
ppm (m, 1H; CH2Ph); 13C NMR (101 MHz, CDCl3): δ 150.7 (s,
2
PCHdCH), 137.6 (s, Ar-Cipso), 136.3 (d, J(C,P) 2.3 Hz, PCHd
1
CH2), 128.9 (s, Ar-C), 128.8 (s, Ar-C), 128.8 (d, J(C,P) 137.8
Hz, PCHdCH2), 126.9 (s, Ar-Cpara), 120.0 (d, 1J(C,P) 119.1 Hz,
2
3
PCHdCH), 67.0 (d, J(C,P) 6.4 POCH2), 38.7 (d, J(C,P) 9.3 Hz,
CHCH2Ph), 36.7 ppm (d, 4J(C,P) 1.3 Hz, CH2Ph); 31P NMR (101
MHz, CDCl3) δ 21.3 ppm; IR (film) ν 1603 (CdC), 1221
(PdO); HRMS (CI) m/z calcd for C13H16O2P [M + H]+ 235.0888,
found 235.0894.
Supporting Information Available: Detailed description
of experimental procedures, NMR spectra, and X-ray crystal
structures of cis-6a, trans-6a, and trans-6f. This material is
General Procedure for the Cross-Metathesis of Cyclic
Phosphinates 5 with Styrene. To a 0.3 M solution of a cyclic
JO0518708
J. Org. Chem, Vol. 70, No. 26, 2005 10809