to give the cyclopropyl ketone 6 (121 mg, 95%) which was
spectroscopically identical to that reported above. A sample was
debenzoylated with potassium tert-butoxide in tert-butanol, as
above, to give the benzyl alcohol 7 with e.e. >95% (n-hexane–
EtOH, 9 : 1).
123.4, 123.3 (Py), 77.1 (PhCH), 75.7 (d, J 15.0, PCH2CH2CH),
25.6 (d, J 72.0, PCH2) and 23.1 (PCH2CH2); m/z(ES) 599
(100%, MNa+) (Found MNa+, 599.1729. C34H29O5N2PNa
requires M, 599.1712); anal. (Found: C, 70.7; H, 5.1; N, 4.9.
C30H29O5PN2 requires C, 70.8; H, 5.1; N 4.9%).
Synthesis of cyclopropane 6 from keto-phosphine oxide 10. A
solution of LDA was prepared by the dropwise addition of n-
butyllithium (0.04 cm3 of a 1.7 mol dm−3 solution in hexane,
68 lmol) to a stirred solution of diisopropylamine (6 mg,
0.06 mmol) in dry tetrahydrofuran (0.5 cm3) at −78 ◦C. The
prepared LDA was added dropwise to a solution of phosphine
oxide 10 (32 mg, 55.7 lmol) in dry tetrahydrofuran (0.5 cm3) at
(1ꢀS,2ꢀS,1ꢀꢀR)-[2ꢀ -{3-Nicotinoyloxy(phenyl)methyl}cyclopro-
pyl](3-nicotinoyl)methanone 27 and (1ꢀS,2ꢀS,1ꢀꢀR)-[2ꢀ-{hydroxy-
(phenyl)methyl}cyclopropyl](3-nicotinoyl)methanone 28. A solu-
tion of LDA was prepared by the dropwise addition of
n-butyllithium (0.32 cm3 of a 1.7 mol dm−3 solution in hexanes,
0.54 mmol) to a stirred solution of diisopropylamine (55 mg,
0.54 mmol) in dry tetrahydrofuran (2.5 cm3) at −78 ◦C. The
prepared LDA was added dropwise to a stirred solution of
phosphine oxide 26 (285 mg, 0.50 mmol) in dry tetrahydrofuran
(2.5 cm3) at −78 ◦C. The reaction mixture was s◦tirred for
◦
−78 C. The reaction mixture was stirred for 11 h, warmed to
0 ◦C and stirred for a further 27 h. The reaction was quenched
with saturated ammonium chloride (0.5 cm3) and the tetrahy-
drofuran was evaporated under reduced pressure and the residue
was extracted with ethyl acetate (3 × 5 cm3). The combined
organic extracts were dried (Na2SO4) and evaporated under
reduced pressure. The residue was chromatographed (SiO2,
hexanes–EtOAc, 2 : 1) to give the starting material (4 mg, 23%)
and, after recrystallisation (from EtOAc), cyclopropyl ketone
6 (15 mg, 76%) as white needles, which was spectroscopically
identical to that reported above.
◦
11 h, subsequently warmed to 0 C and stirred at 0 C for an
additional 27 h. The reaction was quenched with saturated
ammonium chloride (1 cm3) and the tetrahydrofuran was
evaporated under reduced pressure. The residue was extracted
with ethyl acetate (3 × 5 cm3). The combined organic extracts
were dried (Na2SO4) and evaporated under reduced pressure.
The residue was chromatographed (SiO2, EtOAc–hexanes, 1 : 2)
to give the cyclopropane 27 (24 mg, 13%) as a white gum and the
hydroxy-cyclopropane 28 (23 mg, 18%) as a colourless oil. The
cyclopropane 27 had the following data: Rf (EtOAc–hexanes,
2 : 1) 0.21; [a]D23 +7.6 (c 1.2, CHCl3); mmax(CH2Cl2) 3039 (C–H)
Synthesis of cyclopropane 6 from phosphinate oxide 11. A
solution of LDA was prepared by the dropwise addition of n-
butyllithium (0.04 cm3 of a 2.7 mol dm−3 solution in hexanes, 96
lmol) to a stirred solution of diisopropylamine (10 mg, 96 lmol)
=
=
=
1723 (OC O), 1676 (PyC O) and 1590 (C C); dH(400 MHz;
CDCl3) 9.27 (1 H, br s, Py-C2), 9.06 (1 H, br s, Py-C2), 8.79
(1 H, br s, Py-C6), 8.75 (1 H, br s, Py-C6), 8.32 (1H, dt, J 8.0
and 2.0, Py-C4), 8.07 (1 H, dt, J 8.0 and 2.0, Py-C4), 7.49–7.31
(7 H, m, Ar), 5.90 (1 H, d, J 7.5, PhCH), 2.69 [1 H, dt, J 8.0
and 4.5, PyC(O)CH], 2.33 (1 H, dddd, J 8.5, 7.5, 6.5 and 4.0,
PhCHCH), 1.68 (1 H, dt, J 9.0 and 4.5, CHACHB) and 1.42
(1 H, ddd, 8.0, 6.5 and 4.0, CHACHB); dC(125 MHz; CDCl3)
◦
in dry tetrahydrofuran (2 cm3) at −78 C. The prepared LDA
was added dropwise to a solution of phosphinate ester 11 (50 mg,
0.09 mmol) in dry tetrahydrofuran (2 cm3) at −78 ◦C. The
reaction mixture was stirred at −78 ◦C for 11 h, warmed to 0 ◦C
and stirred for a further 27 h. The reaction was quenched with
saturated ammonium chloride (1 cm3) and the tetrahydrofuran
evaporated under reduced pressure. The residue was extracted
with dichloromethane (3 × 10 cm3). The combined organic
extracts were dried (Na2SO4) and the organic layer evaporated
under reduced pressure. The residue was chromatographed
(SiO2, hexanes–Et2O, 2 : 1) to give, after recrystallisation (from
EtOAc), the cyclopropyl ketone 6 (7 mg, 23%) as white needles,
which was spectroscopically identical to that reported above.
(1S,2S)-1,2-Bis(3-nicotinoyloxy)-4-diphenylphosphinoyl-1-phe-
nylbutane 26. Triethylamine (96.0 mg, 0.95 mmol) was added
dropwise to a stirred solution of diol25 25 (71 mg, 0.19 mmol)
and dimethylaminopyridine (43 mg, 0.35 mmol) in dry
dichloromethane (2 cm3) at room temperature. Nicotinoyl
chloride hydrochloride (170 mg, 0.95 mmol) was added and
the reaction was stirred for 18 h. The reaction was quenched
with water (0.5 cm3) and extracted with dichloromethane (3 ×
10 cm3). The combined organic extracts were dried (Na2SO4)
and evaporated under reduced pressure. The residue was
chromatographed (SiO2, EtOAc–MeOH, 19 : 1) to give, after
recrystallisation (from EtOAc–hexanes, 9:1), the bis-nicotinoyl
phosphine oxide 26 (97 mg, 84%) as white needles, m.p.
166–168 ◦C (from EtOAc–hexanes, 9 : 1); Rf (EtOAc–MeOH,
19 : 1) 0.18; [a]D23 +7.9 (c 1.55, CHCl3); mmax(CH2Cl2)/cm−1
=
197.3 (CHC O), 164.4 (CO2), 153.7, 153.4, 150.9, 149.4 (Py),
138.2 (ipso-Ph), 137.2, 135.3 (Py) 132.7 (ipso-Py), 128.9 (ortho-
Ph), 128.8 (para-Ph), 126.8 (meta-Ph), 126.2 (ipso-Py), 123.6,
=
123.4 (Py), 77.7 (PhCH), 29.9 (CHC O), 22.6 (PhCHCH)
and 16.6 (CH2); m/z(EI) 357 [6%, (M − H)+] [Found (M −
H)+, 357.1231. C22H17O3N2 requires M, 357.1239]. The hydroxy
cyclopropane 28 had the following data: Rf (EtOAc–hexane,
2 : 1) 0.18; [a]D23 +4.8 (c 1.1, CHCl3); mmax(CH2Cl2) 3688 (O–H),
=
=
3048 (C–H), 1673 (PyC O) and 1602 (C C); dH(400 MHz;
CDCl3) 9.34–9.20 (1 H, br m, Py-C2), 8.87–8.73 (1 H, br m,
Py-C2), 8.28 (1 H, br d, J 7.5, Py-C4), 7.57–7.47 (1 H, br m,
Py-C5), 7.43–7.27 (5 H, m, Ph), 4.73 (1 H, d, J 5.5, PhCH),
2.75 [1 H, dt, J 8.0 and 4.5, C(O)CH], 2.11 (1 H, J 8.0, 6.5,
5.5 and 4.0, PhCHCH), 1.61 (1 H, ddd, J 8.5, 4.5 and 4.0,
CHACHB) and 1.41 (1 H, ddd, J 8.0, 6.5 and 3.5, CHACHB);
=
dC(125 MHz; CDCl3) 197.9 (C O), 152.5 (Py), 149.0, 142.5
(ipso-Ph), 128.7 (ortho-Ph), 128.2 (para-Ph), 126.2 (meta-Ph),
126.0 (ipso-Py), 123.9 (Py), 73.7 (CHOH), 32.9 (PyCOCH),
22.3 (PhCHOHCH) and 15.5 (CH2); m/z(EI) 252 [8%, (M −
H)+] [Found (M − H)+, 252.1020. C16H14O2N requires M,
252.1024].
=
=
1731 (C O), 1592 (C C) and 1438 (P–Ph); dH(400 MHz;
CDCl3) 9.12 (1 H, d, J 1.5, NCHCCO), 9.10 (1 H, d, J 1.5,
NCHCCO), 8.72 (1 H, dd, J 5.0 and 1.5, NCHCH), 8.69
(1 H, dd, J 5.0 and 1.5, NCHCH), 8.19 (1 H, dt, J 8.0 and
2.0, NCHCHCH), 8.15 (1 H, dt, J 8.0 and 2.0, NCHCHCH),
7.66–7.56 (4 H, m, ortho-PPh), 7.52–7.27 (13 H, m, PPh, Ph and
2 × NCHCH), 6.13 (1 H, d, J 7.5, PhCH), 5.75 (1 H, td, J 7.0
and 6.0, PhCHCH), 2.40–2.20 (2 H, m, PCH2) and 2.05–1.91
(2 H, m, PCH2CH2); dC(100 MHz; CDCl3) 164.6, 164.0 (2 ×
Crystal data for 8: C17H16O2, M = 252.30, orthorhombic,
space group = Pccn, a = 13.1650(8), b = 28.102(2), c = 7.2735(3)
3
−1
˚
˚
A, U = 2690.9(3) A , Z = 8, l(Mo-Ka) = 0.080 mm , 8455
reflections measured at 180(2) K using an Oxford Cryosystems
Cryostream cooling apparatus, 1731 unique (Rint = 0.044); R1 =
0.058, wR2 = 0.118 [I > 2r(I)]. The structure was solved with
SHELXS-97,32 and refined with SHELXL-97.32
Crystal data for 13: C29H27O4P, M = 470.48, orthorhombic,
space group = P2(1)2(1)2(1), a = 10.7399(6), b = 12.8444(8),
3
˚
˚
=
C O), 153.8, 153.7, 150.8, 137.1, 137.0 (Py), 135.4 (ipso-Ph),
c = 17.6182(11) A, U = 2430.4(3) A , Z = 4, l(Mo-Ka) =
0.147 mm−1, 14107 reflections measured at 180(2) K using
an Oxford Cryosystems Cryostream cooling apparatus, 4251
unique (Rint = 0.106); R1 = 0. 069, wR2 = 0.120 [I > 2r(I)]. The
absolute structure parameter (Flack parameter) 0.2(4) indicates
that the absolute structure has been assigned correctly, and this
132.1 (d, J 99.6, ipso-PPh), 132.0 (d, J 99.6, ipso-PPh), 132.0
(d, J 2.5, para-PPh), 131.9 (d, J 2.5, para-PPh), 130.7 (d, J
9.0, ortho-PPh), 130.6 (d, J 9.0, ortho-PPh), 129.2 (para-CPh),
129.0 (ortho-CPh), 128.8 (d, J 12.0, meta-PPh), 128.7 (d, J 11.5,
meta-PPh), 127.3 (meta-CPh), 125.4 (ipso-Py), 125.3 (ipso-Py),
6 3 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 6 3 0 – 6 3 7