300 J . Org. Chem., Vol. 62, No. 2, 1997
Marinetti et al.
Hz, Hendo, CH2-7), 1.8-2.0 (m, 2H, CH-1 and CH-5), 2.1-2.3
(m, 2H, CH2-4 and CH2-7), 2.5-2.7 (m, 2H), 4.73 (td, 3J ) 10.1,
3J ) 7.5 Hz, 1H, CHCl); 13C NMR (CDCl3) δ 55.8 (CHCl). [R]D
+ 25° (neat).
highly diastereoselective reaction and its potential in
asymmetric synthesis are under investigation.
Moreover, analogous reactions between phosphorus
derivatives, electron rich olefins, and strong, non nucleo-
philic acids, e.g. HBF4, may provide a rather general and
direct synthetic approach to phosphorus-carbon bonds,
when suitably developed.
Syn th esis of th e Dich lor op h osp h in es 4 a n d 6. Mag-
nesium (1.0 g, 45 mmol) and ethyl bromide (0.1 mL) were
stirred for 15 min in 10 mL of refluxing ether (for the synthesis
of 4) or at 50 °C in 10 mL of THF (for the synthesis of 6). A
solution of the chloride (6.0 g, 35 mmol) in 15 mL of dry solvent
(ether for 1 and THF for 3a ) was then added slowly. During
the addition of 1, the reaction temperature was maintained
at about 40 °C. With 3a a slightly exothermic reaction was
observed. Formation of the Grignard reagent was completed
by heating the mixture at 50-60 °C for about 30 min. After
cooling to rt, the solution was decanted into a pressure-
equalizing dropping funnel and added dropwise to a stirred
solution of PCl3 (3.3 mL, 38 mmol) in 50 mL of dry ether at
-78 °C. The mixture was allowed to rise to rt and filtered
under argon. (In the case of 6, the solvents ether-THF were
evaporated under vacuum, ether was added, and the mixture
was filtered). The solvent and the excess PCl3 were removed
under vacuum to give the crude product which was distilled
in a kugelrohr apparatus at about 110 °C/0.1 mm.
Exp er im en ta l Section
Gen er a l Meth od s. All reaction solvents were distilled
immediately prior to use. THF and ether were distilled from
sodium/benzophenone. All reactions were carried out under
an argon atmosphere. Neutral aluminum oxide (50-160 µm,
Prolabo) and Florisil (100-200 mesh, Aldrich) were used for
chromatographic separations. NMR spectra were recorded at
1
200.13 MHz for H, 50.32 MHz for 13C, and 81.01 MHz for 31P.
13C NMR assignments are based on literature data,16-18 DEPT
135 experiments and, eventually, 1H-13C correlations. Se-
lected NMR data are given below. Elemental analyses were
performed by the “Service d’Analyse du CNRS”, Gif sur Yvette,
France. Optical rotations were measured at room tempera-
ture. All commercially available reagents were used as
received from the suppliers, unless otherwise stated.
(1S)-cis-Myr ta n yld ich lor op h osp h in e (4): was obtained
in 48% yield (4.0 g); bp 84 °C/0.1 mm. It contains less than
5% of a second dichlorophosphine observed in the 31P NMR
spectrum. 4: colorless, air sensitive liquid; 31P NMR (CDCl3)
δ 197.5; 1H NMR (CDCl3) δ 0.97 (d, 2J ) 9.8 Hz, Hendo, CH2-7),
1.07 (s, Me), 1.22 (s, Me), 1.5-2.6 (m); 13C NMR (CDCl3) δ 52.9
(J C-P ) 44.9 Hz, CH2P). Mass spectrum (35Cl) m/z 238 (M,
4%), 223 (M - Me, 16%), 81 (100%).
Gen er a l P r oced u r e for th e Syn th esis of th e Alk yl
Ch lor id es 1, 2b, a n d 3a . A solution of the appropriate alcohol
(12 g, 78 mmol) and triphenylphosphine (40.9 g, 156 mmol) in
CCl4 (220 mL) was refluxed for 16 h. After cooling to rt, about
200 mL of hexane were added, and the white precipitate of
triphenylphosphine oxide was removed by filtration. After
evaporation of the solvent, the mixture was eventually ex-
tracted with hexane and filtered in order to remove the
residual Ph3PO. Fractional distillation afforded the desired
chloride.
(1S,2R)-2-(Ch lor om et h yl)-6,6-d im et h ylb icyclo[3.1.1]-
h ep ta n e (1). (1S)-cis-myrtanyl chloride was obtained from
(1S)-myrtanol (prepared by hydroboration-oxidation of (1S)-
(-)-â-pinene [R]D -21° (neat) according to ref 3b). Fractional
distillation afforded 9.0 g of 1 (67%) (98 °C/15 mm). 1H NMR
(CDCl3) δ 0.94 (d, 2J ) 9.7 Hz, Hendo, CH2-7), 0.98 (s, Me), 1.20
(s, Me), 3.47 (AB, J AB ) 10.5, 3J ) 1.0 Hz, 1H, CH2Cl), 3.56
(AB, 3J ) 0.8 Hz, 1H, CH2Cl); 13C NMR (CDCl3) δ 50.2 (CH2Cl).
Selected NMR and physical data have been reported.3a,b
(1S )-exo-2-C h lo r o -1,7,7-t r i m e t h y lb i c y c lo [2.2.1]-
h ep ta n e (2b). (1S)-exo-isobornyl chloride was obtained from
(1S)-endo-borneol (Aldrich, [R]D -35.3 (c ) 5, EtOH). Frac-
tional distillation under vacuum (0.1 mm) afforded the olefinic
dehydration byproduct, bornylene (0-25 °C, trapping at -78
°C), containing only very small amounts of the chloride. The
desired chloride 2b was subsequently obtained in 65% yield
(8.7 g) by sublimation at 40-50 °C (0.1 mm) as a colorless solid.
Selected 1H NMR (CCl4)17a and 13C NMR (CS2)17b data have
been reported. 1H NMR (CDCl3) δ 0.85 (s, Me), 1.00 (s, Me),
1.09 (s, Me), 2.01 (AB, J AB ) 13.8, 3J ) 8.4 Hz, 1H, CH2-3),
2.2 (AB, m, 1H, CH2-3), 3.95 (dd, 3J ) 8.4, 3J ) 4.7 Hz, 1H,
CHCl); 13C NMR (CDCl3) δ 68.3 (CHCl). Anal. Calcd for
(1R)-exo-Isop in oca m p h eyld ich lor op h osp h in e (6): ob-
tained in 79% yield (6.6 g) as a colorless liquid; 31P NMR
1
2
(CDCl3) δ 185.0; H NMR (CDCl3) δ 0.92 (dd, J ) 10.1 Hz, J
) 2.4 Hz, Hendo, CH2-7), 1.07 (s, Me-8), 1.23 (s, Me-9), 1.25 (d,
3J ) 8 Hz, Me-10), 1.8-2.6 (m); 13C NMR (CDCl3) δ 45.5 (J C-P
) 47.3 Hz, CHP). Mass spectrum (35Cl) m/z 238 (M, 2%), 137
(M - PCl2, 22%), 81 (100%). [R]D -54° (c ) 1, CHCl3).
Syn th esis of th e (1S)-en d o-Bor n yld ich lor op h osp h in e
(5a ). (Et2N)2PCl was prepared from PCl3 and diethylamine
according to ref 10 and distilled at 62-66 °C/1 mm. The
Grignard reagent prepared from exo-isobornyl chloride 2b (6.0
g, 35 mmol) and magnesium (1.0 g, 45 mmol) in THF (25 mL)
was decanted and added dropwise to a stirred solution of
(Et2N)2PCl (7.4 g, 35 mmol) in diethyl ether (50 mL) at -78
°C. The temperature was allowed to rise and the formation
of 7 was checked by 31P NMR: δ ) 93. The reaction mixture
was cooled to 0 °C, and gaseous HCl was bubbled through the
solution for about 5 min. The oily-solid insolubles were
decanted or filtrated, and the solvent was removed under
vacuum. The crude product was distilled on a kugelrohr
apparatus at about 110 °C/0.1 mm. 5a was obtained in 70%
yield (5.9 g) after distillation. The isomeric 5b was not
detected by 31P NMR spectroscopy. 5a : 31P NMR (CDCl3) δ
197.3; 1H NMR (CDCl3) δ 0.87 (d, 4J H-P )1.0 Hz, Me-10), 0.93
(s, Me), 1.07 (s, Me), 2.17 (m, 1H), 2.65 (m, PCH); 13C NMR
(CDCl3) δ 28.3 (CH2), 31.6 (J C-P ) 29.0 Hz, CH2), 33.8 (J C-P
)
C10H17Cl: C, 69.55, H, 9.92. Found: C, 69.98, H, 9.32, [R]D
52° (c ) 1, CHCl3).
+
21.6 Hz, CH2), 56.6 (J C-P ) 49.9 Hz, CHP). Mass spectrum
(35Cl) m/z 239 (M + 1, 26%), 137 (M - PCl2, 100%), 95 (26%),
81 (37%). [R]D -22° (c ) 1.6, CHCl3).
(1R )-en d o-3-C h lo r o -2,6,6-t r im e t h y lb ic y c lo [3.1.1]-
h ep ta n e (3a ). (1R)-neoisopinocampheyl chloride 3a was
obtained from (1R)-isopinocampheol (prepared by hydro-
boration-oxidation of (1R)-(+)-R-pinene of 91% ee according
to ref 8). The final mixture was separated by fractional
distillation: the byproduct, R-pinene, was recovered at 25 °C/
0.5 mm, and then 3a was recovered (30 °C, 0.1 mm) in 30%
yield (3.6 g). 1H NMR (400 MHz) (CDCl3) δ 1.08 (s, Me-8),
Syn th esis of th e P h osp h eta n e Oxid es 8-10. AlCl3 was
sublimed under argon at 170 °C immediately prior to use. To
0.32 g (2.4 mmol) of aluminum chloride in 2 mL of CH2Cl2 was
added at 0 °C a solution of 0.50 g (2.1 mmol) of dichlorophos-
phine and 0.32 mL (2.3 mmol) of 2,3,3-trimethylbutene in 1
mL of methylene chloride. The reaction mixture was stirred
at 0 °C for about 20 min, warmed to rt (31P NMR of the
3
2
-
intermediate phosphetanium salts R3PCl2+AlCl4
: 8′ δ )
1.21 (s, Me-9), 1.23 (d, J ) 7.8 Hz, Me-10), 1.24 (d, J ) 10.4
113.0, 112.6 (ratio 1.4:1); 9′ δ ) 120.1, 117.3 (ratio 5:1); 10′ δ
) 123.6, 119.0 (ratio 1:1)), and then hydrolyzed slowly at 0 °C
with distilled water. The organic layer was separated, washed
with water, and finally dried over MgSO4. The final product
was purified by column chromatography on neutral alumina
with hexane-ethyl acetate 60:40 as eluent (Rf ) 0.3).
(16) Coxon, J . M., Hydes, G. J ., Steel, P. J . J . Chem. Soc., Perkin
Trans. 2 1984, 1351.
(17) (a) Brown, H. C.; Liu, K.-T. J . Am. Chem. Soc. 1975, 97, 600.
(b) Lippmaa, E.; Pehk, T.; Paasivirta, J .; Belikova, N; Plate´, A. Org.
Magn. Reson. 1970, 2, 581.
(18) Gray, G. A., Cremer, S. E. J . Org. Chem. 1972, 37, 3458.
(19) X-ray data have been deposited at the Cambridge Crystal-
lographic Data Centre.
1-Myr t a n yl-2,2,3,3-t et r a m et h ylp h osp h et a n e
Oxid e
(8a ,b): obtained from myrtanyldichlorophosphine in 61% yield