Stereospecificity of the 1,2-Wittig Rearrangement: How Chelation Effects Influence Stereochemical Outcome

Since its discovery the rearrangement of R-metalated ethers, particularly the [2,3]-Wittig rearrangement, has been the subject of intensive mechanistic and synthetic investigations.1 Relative to the [2,3]-shift, the [1,2]-Wittig rearrangement has received relatively little publicity. Most studies of the [1,2]-Wittig have been mechanistic in origin, resulting in the widely accepted theory that the reaction proceeds via a radical pair dissociationrecombination mechanism.2 Several years ago, Schreiber3 reported an important observation on the stereospecific nature of this rearrangement (Scheme 1). Deprotonation of 1 resulted in “synthetically useful levels” of the [1,2]-rearrangement product that was heavily biased toward the syn isomer 3. Schreiber postulated that the product arose from bond reorganization via a diradical transition state in which a lithium tether 2 sets up the syn stereochemistry. Another surprising feature of this rearrangement was the high level of retention (94%) at the migrating center. This observation became more interesting upon Cohen’s4 and Brückner’s5 recent evidence that [1,2]-Wittig rearrangements proceeded with inversion of the lithium-bearing terminus. Nakai6 addressed this question and showed clearly that the [1,2]-Wittig rearrangement of enantiodefined R-alkoxylithium species proceeds with retention of the migrating center and with inversion of the lithium-bearing terminus (Scheme 2). In these examples, the stereochemistry of the product alcohols is not the result of chelation control, but rather decided by the configuration of the stannane precursor. While there is little argument with either mechanistic explanation for the observed stereochemistries, it is important to note that the enantiodefined stannanes studied by Nakai did not hold the possibility of rearrangement under chelation control.7 We found it intriguing to consider substrates with an ether oxygen capable of coordinating with the lithium of the stereodefined lithium terminus. In such substrates the appropriate stereochemical combination could put Schreiber’s mechanism in stereochemical conflict with the results of Nakai, Cohen, and Brückner (Scheme 3). We therefore sought to prepare and study such substrates to provide a deeper understanding of the [1,2]-Wittig rearrangement. We believed that knowledge of the stereochemical influences imparted by these two mechanistic pathways would allow the discovery of new reaction conditions which should enable the practitioner to predict and control the stereochemical course of the [1,2]-Wittig rearrangement. Such reaction control would be of considerable value as it would represent a means for the selective construction of either synor anti-1,3 polyols, via a common reaction manifold. Our preliminary experiments began with the preparation of the enantiodefined stannanes 6, 9, 10, and 11. The syntheses of these compounds paralleled established procedures8 and involved the displacement of the known enantiodefined stannyl mesylates9 (R)13 and (S)-13 by the alkoxides of erythro and threo forms of 1-C-phenyl-2,3-O-isopropylidene-D-glycerol10 (Scheme 4). This method provided the desired stannanes in 87% yield and in greater than 95% de as judged by the 1H NMR. Once model compounds 6, 9, 10, and 11 were in hand, the [1,2]-Wittig rearrangement reaction was investigated. Compound 6 was first exposed to n-BuLi in 30% THF/hexanes, the same solvent system employed by Schreiber. The reaction gave a 64% (1) (a) Nakai, T.; Mikami, K. Chem. ReV. 1986, 86, 885-902. (b) Marshal, J. A. In ComprehensiVe Organic Synthesis; Pattenden, G., Ed.; Pergamon: London, 1991; Vol. 3, pp 975-1014. (2) (a) Schäfer, H.; Schöllkopf, U.; Walter, D. Tetrahedron Lett. 1968, 2809-2814, and references therein. (b) Evans, D. A.; Baillargeon, D. J. Tetrahedron Lett. 1978, 3315, 3315-3322. (c) Azzena, U.; Denurra, T.; Melloni, G.; Piroddi, A. M. J. Org. Chem. 1990, 55, 5532-5535. (d) Tomooka, K.; Yamamoto, H.; Nakai, T. J. Am. Chem. Soc. 1996, 118, 3317-3318. (e) Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann. Chem. 1997, 12751281. (3) (a) Schreiber. S. L.; Goulet, M. T. Tetrahedron Lett. 1987, 28, 10431046. (b) Goulet, M. T. Ph.D. Thesis, Yale University, 1988. (4) Verner, E. J.; Cohen, T. J. Am. Chem. Soc. 1992, 114, 375-377. (5) Hoffmann, R.; Brückner, R. Chem Ber. 1992, 125, 1957-1963. (6) (a) Tomooka, K.; Igarashi, T.; Nakai, T. Tetrahedron Lett. 1993, 34, 8139-8142. (b) Tomooka, K.; Igarashi, T.; Nakai, T. Tetrahedron 1994, 50, 5927-5932. (7) Nakai has reported chelation-controlled rearrangements of racemic lithio species (see ref 2e). (8) Tomooka, K.; Igarashi, T.; Watanabe, M.; Nakai, T. Tetrahedron Lett. 1992, 33, 5795-5798. (9) Matteson, D. S.; Tripathy, P. B.; Sarkar, A.; Sadhu, K. M. J. Am. Chem. Soc. 1989, 111, 4399-4402 and references therein. (10) (a) Ohgo, Y.; Yoshimura, J.; Kono, M.; Sato, T. Bull. Chem. Soc. Jpn. 1969, 42, 2957-2961. (b) Mulzer, J.; Angermann, A. Tetrahedron Lett. 1983, 24, 2843-2846. Scheme 1. [1,2]-Wittig Rearrangement Where Chelation Sets the Stereochemistry of the Newly Formed Alcohol3