April 1998
SYNLETT
423
1:PhCONEt = 2:8; 1:PhOCONEt = < 5: > 95. With the appropriate
References and Footnotes
2
2
18
caveat, these results suggest an order of metalation power, DMG =
1.
Current address: SmithKline Beecham Pharmaceuticals, New
Frontiers Science Park, Harlow, Essex, CM19 5AW, UK.
t
OCONEt > CONEt > P(O) Bu > OMe.
2
2
2
t
As an initial indication of cooperative metalation effects of the P(O) Bu
2
2.
Current address: Department of Medicinal Chemistry, The Royal
Danish School of Pharmacy, Universitetsparken 2, DK-2100,
Copenhagen, Denmark.
t
17
DMG, lithiation - BuNCO quench of 7a provided a 8:1 ratio (56%
combined isolated yield) of 8 and 9. Similarly, metalation - TMSCl
17
quench of 7b, afforded 8 as the only isolable product.
3.
4.
Snieckus, V. Chem. Rev. 1990, 90, 879.
a) Stuckwisch, C. G. J. Org. Chem. 1976, 41, 1173; b) Dashan, L.;
Trippett, S. Tetrahedron Lett. 1983, 24, 2039; c) Yoshifuji, M.;
Ishizuka, T.; Choi, Y. J.; Inamoto, N. Tetrahedron Lett. 1984, 25,
553; d) Schaub, B.; Jenny, T.; Schlosser, M. Tetrahedron Lett.
1984, 25, 4097; e) Craig, D. C.; Roberts, N. K.; Tanswell, J. L.
Aust. J. Chem. 1990, 43, 1487.
5.
Thus treatment of Ph PO with t-BuLi leads, in addition to ortho-
3
metalation, to Ph displacement by t-Bu, and further ortho-
lithiation: see ref 4d and Seyferth, D.; Welch, D. E.; Heeren, J. K.
J. Am. Chem. Soc. 1964, 86, 1100.
6.
7.
Schmid, R.; Foricher, J.; Cereghetti, M.; Schönholzer, P. Helv.
Chim. Acta 1991, 74, 370.
Brown, J. M.; Woodward, S. J. Org. Chem. 1991, 56, 6803;
Alcock, N. W.; Brown, J. M.; Pearson, M.; Woodward, S.
Tetrahedron Asymmetry 1992, 3, 17.
Scheme 3
8.
9.
Bader, A.; Lindner, E. Coord. Chem. Rev. 1991, 108, 27.
Togni, A. Chimia 1996, 50, 86.
In pursuit of chemistry of potential value for ligand studies, phosphine
oxide 2i (Scheme 4) was reduced with trichlorosilane to give the
unsymmetrical bisphosphine 10 and 2k was subjected to typical
Ullmann homocoupling conditions to afford the 2,2'-bisphosphinyl
biaryl 11 in excellent yield. Attempts to further metalate 11 were
unsuccessful, results which may be understood on the basis of the single
crystal X-ray analysis of 11 which shows alignment of both oxygens
towards the centres of the opposite rings thereby placing them in
unfavourable orientation for directing ortho-deprotonation.
10. Supported by X-ray crystal structure data (2.498 Å).
11. Complete crystallographic data for compounds 1, 2f, and 11 has
been deposited with the Cambridge Crystallographic Data Centre.
12. Mann, B.E.; Shaw, B.L.; Slade, R.M. J. Chem. Soc. (A) 1971,
2976.
11
13. Compound 1 was also prepared (44% yield) by treatment of
phenyldichlorophosphine with t-BuLi (2 equiv) in toluene at 0°C
followed by reflux (12 h) and hydrogen peroxide oxidation.
Although less general, this method is particularly useful for
preparation of large quantities of 1. The use of toluene as the
solvent is crucial; in THF or Et O, no product was isolated.
2
14. Typical Experimental Procedure. To
a solution of di-t-
butylphenylphosphine oxide (1) (302 mg, 1.27 mmol) in anhyd
THF (8 mL) at < -70°C (CO /acetone bath) was added dropwise t-
2
BuLi (0.99 mL, 1.39 mmol, 1.4 M in pentane) and the reaction
mixture was stirred (80 min). The yellow suspension was treated
via cannula with a solution of I (354 mg, 1.39 mmol) in THF (5
mL) and the resulting red solution was warmed to rt over 8-10 h.
2
Scheme 4
Addition of aq Na S O and standard work up, followed by flash
2
2 3
t
In summary, this work has introduced the P(O) Bu ortho-metalation
2
chromatography (5:1 EtOAc/hexane eluent) afforded 352 mg
(76% yield) of 2k as a colourless solid, mp 164.5-165°C (Et O/
group for the regiospecific synthesis of new P-based aromatics,
evaluated its relative hierarchy with respect to several other DMGs, and
revealed its potential for the construction of new phosphorus ligands.
Extension and application of these preliminary results is under active
study.
2
-1
1
CH Cl ); IR (KBr) 1164 cm ; H NMR (CDCl , 250 MHz) δ
2
2
3
8.15 (ddd, 1H, J = 1.3, 2.1, 8.0 Hz), 7.54 (ddd, 1H, J = 1.5, 7.6, 7.7
Hz), 7.37 (dddd, 1H, J = 1.4, 2.2, 7.5, 7.7 Hz), 7.09 (dddd, 1H, J =
13
1.5, 3.0, 7.6, 7.7 Hz), 1.33 (d, 18H, J = 13.6 Hz); C NMR
(CDCl , 63 MHz) 144.4 (d, J = 8.0 Hz), 132.5 (d, J = 11.4 Hz),
3
131.7, 131.3 (d, J = 76.5 Hz), 125.8 (d, J = 10.0 Hz), 98.7, 37.2 (d,
Acknowledgements
+
J = 59.1 Hz), 27.5; m/z (EI) 364 (M ); Anal Calcd for C
H IOP:
14 22
We are grateful to NSERC Canada and Monsanto (Industrial Research
Chair program) and URIF Ontario for financial support. We warmly
thank Dr. Dennis Phillion, Monsanto for suggesting this research and
Dr. Mike Campbell for MM2 force field calculations (SYBYL 6.2).
C, 46.17; H, 6.09; P, 8.50. Found: C, 45.95; H, 5.89; P, 8.69.
15. Crystal data for 2f: C BO P, M = 365.28, monoclinic, C2/c,
H
20 35
3
r
a = 20.663(2), b = 13.337(1), c = 15.604(2) Å, β = 101.745(7)°, V
3
3
= 4210.0(10) Å , Z = 8, F(000) = 1592, D = 1.153 g/cm , T =
c
160K. Data were collected on a Siemens P4 Diffractometer with
MoKα radiation (λ = 0.71073 Å). A total of 3689 independant
reflections were measured. The structure was solved using direct