produced by the catalyst when a matching between the
chirality of the backbone and the chirality of the P/O
heterocycle exists.8
pseudo-ortho-Disubstituted paracyclophane has planar
chirality. The chiral phosphine PhanePhos (4,12-bis(di-
phenylphosphino)-[2.2]-paracyclophane) (Figure 1) based on
phino)paracyclophane (4)12 was found to be a convenient
general intermediate. The reaction of 4 with the conjugate
bases of a number of diols and phenols proceeded smoothly
and provided the corresponding phosphonites in good yields.
A range of phenols, as well as aromatic and aliphatic diols,
was tested.13 Biaryl diols emerged as the best complement
to the chirality of the paracyclophane backbone.
Phosphonites 1a-c derived from 2,2′-biphenol (1a), 2,2′-
binaphthol (Binol) (1b), and 3,3′-di-tert-butyl-5,5′,6,6′-
tetramethyl-biphenol (1c) were isolated and characterized by
NMR spectroscopy (Figure 2).12 All phosphonites 1a-c were
Figure 1.
this backbone has been very successfully used in rhodium-
catalyzed hydrogenations of dehydroamino acids9 and in
ruthenium-catalyzed hydrogenation of ketones.10 No attempt
has so far been reported to expand the range of ligands based
on this backbone by replacing two P-C bonds with two P-O
bonds. The preparation of such ligands of general structure
1 (Figure 1), their metal complexes, and their application to
asymmetric catalysis was a previously unexplored area.
Enantiomerically pure pseudo-ortho-dibromo-paracyclo-
phane (2, 4,12-dibromo-paracyclophane)11 was the starting
material for the chemistry described herein. Although various
procedures have been reported for the synthesis of phos-
phonites, we found that a stepwise procedure via intermedi-
ates 3 and 4 was easy to implement and flexible and
eventually yielded clean products (Scheme 1).
Figure 2.
relatively insoluble in MeOH and were isolated from the
crude reaction by simply removing the reaction solvent and
washing the product with MeOH (the salts generated in the
reaction being soluble in MeOH). Configurationally flexible
2,2′-biphenol could give rise, in principle, to different
diastereoisomers with the two P/O heterocycles having (R/
R), (S/S), or (R/S) configuration. The 31P NMR spectrum,
however, indicated that in effect compound 1a was isolated
as a single diasteroisomer.
Scheme 1. Synthesis of Phosphonites 1
The rhodium complexes of general formula [(1a-c)-Rh-
COD]BF4 were prepared by reacting ligands 1a-c with
[Rh(COD)2]BF4 in dichloromethane at room temperature.
When phosphonites 1c bearing bulky P/O units were used,
only the “matched” ligand (S)-1-(R)-c gave the desired
rhodium complex. The “mismatched” ligand (S)-1-(S)-c did
not react with [Rh(COD)2]BF4.
The catalysts derived from rhodium complexes [(1a-c)-
Rh-COD]BF4 were tested in the catalytic hydrogenation of
(8) A similar concept has recently been applied to the synthesis of
phosphite ligands; see ref 4.
(9) Pye, P. J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.;
Reider, P. J. J. Am. Chem. Soc. 1997, 119, 6207.
(10) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.; Zanotti-Gerosa,
A. Org. Lett. 2000, 2, 4173.
(a) (i) t-BuLi, Et2O, -78oC; (ii) ClP(NR2)2, rt, 74-84% yield;
(b) HCl in Et2O, rt, 62-73% yield; (c) Li salts of the diol, THF,
rt, 48-72% yield.
(11) Pye, P. J.; Rossen, K.; Volante, R. P. Merck & Co., PCT Appl.
WO 97/47632, 1997. Pye, P. J.; Rossen, K.; Volante, R. P., Maliakal, A. J.
Org. Chem. 1997, 62, 6462.
Metalation of the dibromo precursor 2 with t-BuLi,
followed by reaction with an appropriate chloro diamino-
phosphine gave products 3a-b.12 These compounds were
transformed into 4 by treatment with a solution of hydrogen
chloride in diethyl ether. pseudo-ortho-Bis(dichlorophos-
(12) See Supplementary Information
(13) The ligands derived from 2,6-dimethylphenol, 2-naphthol, both
enantiomers of TADDOL and 1,2-diphenyl-ethane-diol, were prepared and
tested in rhodium-catalysed hydrogenation of dehydroamino acids. The
results were inferior to the ones obtained with ligands 1a,b.
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Org. Lett., Vol. 3, No. 23, 2001