Katsuhiko Tomooka

Asymmetric [2,3]-Wittig rearrangement as a general tool for asymmetric synthesis

Recent advances in the asymmetric (2,3)-Wittig rearrangement as a general tool for asymmetric synthesis of homoallylic alcohols are described. First, the synthetic utilities of the asymmetric transmission type and the two asymmetric induction types are demonstrated, including applications in asymmetric syntheses of natural products and steroid side chains. Second, some examples are presented of the enantioselective versions involving a chiral ligand-bound boron enolate and organolithium as the migrating terminus. Finally, the mechanistic grounds of the asymmetric versions are discussed on the basis of the stereochemical analyses of the asymmetric version involving an enantiomerically-defined carbanion terminus. The (2,3)-Wittig rearrangement is a special class of (2,3)-sigmatropic rearrangement which involves an a- oxy carbanion as the migrating terminus to afford various types of homoallylic alcohols. As can be seen in the general formula (eq. l), this type of carbanion rearrangement possesses synthetically valuable features, including (a) the regiospecific carbon-carbon bond formation with allylic transposition of the oxygen function, (b) the stereoselective formation of a new olefinic bond, and (c) the stereoselective creation of vicinal chiral centers. Thus, the (2,3)-Wittig rearrangement currently enjoys widespread application in many facets of organic synthesis, particularly in the context of acyclic stereocontrol and natural product synthesis (ref. 1). The most significant feature is its ability of efficient diastereocontrol over the newly-created chiral centers through the proper choice of the combination of G group and substrate geometry. Some of the highly diastereoselective variants thus developed are shown below which provide a higher than 95% of either threo or erythro diastereoselectivity (refs. 1, 2).

[2,3]Wittig rearrangement of enantiomerically-defined α-(allyloxy)stannanes: Solid evidence for inversion of configuration at the lithium- bearing migrating terminus

Abstract The [2,3]Wittig rearrangement of enantiomerically-defined α-(allyloxy)stannanes, prepared from (S)-1-tributylstannyl-1-propanol, with butyllithium is shown to proceed with essentially complete inversion of configuration at the lithium-bearing migrating terminus. This inversion stereochemistry is further confirmed by the rearrangement of diastereomerically-defined α-(allyloxy)stannanes.

Directing group-controlled hydrosilylation: Regioselective functionalization of alkyne

Pt(0)-catalyzed hydrosilylation of unsymmetric alkynes proceeds in a highly regioselective manner with a dimethylvinylsilyl (DMVS) group as the directing group. This hydrosilylation affords a single regioisomer of silylalkenes from propargylic and homopropargylic alcohol derivatives. DMVS also has an accelerating effect that allows group-selective hydrosilylation of the DMVS-attached alkyne prior to that of other alkynes. Combined hydrosilylation and transformation reactions of the resulting silylalkenes afford various tri-substituted alkenes and multi-oxy-functionalized compounds with high regioselectivity from unsymmetric alkynes.

Enantioselective Synthesis of Silanol

An enantioselective nucleophilic substitution reaction of achiral dialkoxysilane has been developed. The reaction proceeds with efficient stereocontrol on the silicon chirality center to give the enantioenriched silyl ether, which can be converted to the silanol without loss of enantiopurity. We have analyzed the steric course of the reaction by using DFT calculations and propose a transition state model to explain the observed enantioselectivity.

Direct Thioamination of Arynes via Reaction with Sulfilimines and Migratory N-Arylation

A novel method for preparing a diverse range of o-sulfanylanilines is described. Direct thioamination of arynes with sulfilimines gives o-sulfanylanilines, involving C-N and C-S bond formations and migratory N-arylation.

Catalytic enantioselective synthesis of alkenylhydrosilanes

Nonracemic silanes possessing a silicon stereocenter have structural similarity to their carbon congeners, but show substantial differences in their physical and electronic properties. Therefore, nonracemic silanes have attracted attention in the fields of synthetic, material, and bioorganic chemistry. Despite their potential importance, nonracemic silanes are unavailable in nature, and therefore the development of an efficient asymmetric method for their preparation is eagerly awaited. Among the several possible methods for the asymmetric synthesis of chiral silanes, desymmetrization of achiral silanes A would be the most rational approach (Scheme 1). Previously, we had developed asymmetric syn-

Enantioselective [2,3]-Wittig rearrangement induced by asymmetric lithiation with a t-butyllithium/chiral bis(oxazoline) system

Abstract The [2,3]-Wittig rearrangement of (E)-crotyl propargylic ethers, when induced with a t-BuLi/chiral bis(oxazoline) complex, is shown to provide high enantioselectivity (up to 89% ee) along with high diastereoselectivity.

External chiral ligand-induced enantioselective lithiation/SE2 reactions of isochroman and phthalan

Abstract Treatment of isochroman and phthalan with a t-BuLi/chiral bis(oxazoline) complex followed by reaction with carbon-electrophiles such as benzaldehyde and CO2 is shown to afford the α-substituted derivatives in moderate-to-high enantioselectivities (up to 97% ee and 83% ee, respectively). The asymmetric induction is proved to occur at the post-lithiation step.

Enantioselective synthesis of planar chiral organonitrogen cycles

Enantioselective synthesis of a planar chiral organonitrogen cycle has been newly developed based on the unprecedented prochiral face-selective cyclization of achiral linear precursors by an appropriate chiral promoter.

Enantioselective carboxylation of α-methoxybenzyllithium generated via asymmetric lithiation with a t-BuLi/chiral bis(oxazoline) complex

Abstract Treatment of benzyl methyl ether with a t -BuLi/chiral bis(oxazoline) complex followed by carboxylation is shown to afford α-methoxy phenylacetic acid in high % ee (up to 95%). The asymmetric induction was proved to occur at the post-lithiation step.