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Alpha rules: A thiourea acts as an efficient organocatalyst for the glycosylation of protected galactals to form oligosaccharides containing a 2-deoxymonosaccharide moiety. The reaction is highly stereoselective for α-linkages and proceeds by way of a syn-addition mechanism.

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A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α-selectivity and yields (77–97 %) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH⋅H2O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.

Heterocycling: Diphenyl vinyl sulfonium salt 1 acts first as an electrophile, then a base, and then again as an electrophile in this operationally simple, high yielding, one‐pot synthesis of pharmacologically important morpholines, thiomorpholines, and piperazines. Compound 1 is an excellent synthon for the 1,2‐ethane dication.

Heating one of the most abundant naturally occurring inorganic chemicals (elemental sulfur) with one of the most readily available homochiral molecules (limonene) gives a one-step synthesis of a chiral sulfide which exhibits outstanding selectivities in sulfur ylide mediated asymmetric epoxidations and aziridinations. In particular reactions of benzyl and allylic sulfonium salts with both aromatic and aliphatic aldehydes gave epoxides with perfect enantioselectivities and the highest diastereoselectivities reported to date. In addition reactions with imines gave aziridines again with the highest enantioselectivities and diastereoselectivities reported to date. The reactions are scaleable, and the sulfide can be reisolated in high yield. The epoxidation has been used as the key step in a convergent and stereoselective synthesis of each of the diastereoisomers of the cinchona alkaloids, quinine and quinidine.

Chiral nonracemic phosphorus compounds are ubiquitous in catalytic asymmetric synthesis, both as ligands in metal-based processes 1 and as organocatalysts in their own right. 2 However, although a very large number of such ligands have been tested, the great majority have their chirality located on the carbon backbone (C-stereogenic, e.g., BINAP and DuPHOS) 1a instead of on the phosphorus atom (P-stereogenic, e.g., DiPAMP). 1c This is despite the fact that better chiral induction might be expected by incorporation of chirality as close as possible to the catalytic center. 3 Although P-stereogenic ligands have proven to be effective, 4 relatively few have been studied because they are difficult to synthesize. 5 Early methods were based on resolution and the generation of unequal mixtures of diastereomers, 5a while more recent strategies include desymmetrization, enzymatic resolution, and catalytic asymmetric synthesis. 5b,6 Some of these methods can be very effective, but most are limited in scope in some way and there remains a clear need for a general solution. Herein we report on our efforts to provide such a methodology.We have been interested in this difficult problem for some time. 7 We felt that there was promise in strategies involving kinetic resolution (KR) or dynamic kinetic resolution (DKR) in P(III)/P(V) interconversions (Scheme 1). Our initial approach centered on KR in asymmetric reduction (Scheme 1a), but this gave uniformly low selectivity, 7a in line with previous reports, 8 and we turned our attention to asymmetric oxidation (Scheme 1b). There have been very few reported successes at KR/DKR in such systems, 5a,9 most notably by Perlikowska et al. 9a who reported up to 39% ee in the KR of P-stereogenic tertiary phosphines and 70% ee for a single example of the first DKR of a chlorophosphine. In our early experiments, 7b,c we reacted racemic phosphines with chiral nonracemic epoxides hoping that the high temperature of the reaction would allow DKR through racemization of the phosphine, but the selectivity was low (20% at best).A way to achieve facile interconversion of stereogenic phosphorus centers at low temperatures is via pseudorotation of pentavalent pentacoordinate phosphorus compounds (10P5). 10 We therefore explored a variety of processes that could involve 10P5, and we report now our preliminary results on an asymmetric version of the oxidation/reduction/dehydration system known as the Appel conditions. 11 Typically, these conditions involve use of PPh 3 /CCl 4 to convert an alcohol to an alkyl chloride in high yield. From our perspective, these conditions are an oxidation of a phosphine involving a potentially chiral reagent (Scheme 2). Therefore, we were encouraged when our first experiments with this system gave some selectivity. Treatment of racemic phenyl-ortho-anisylmethylphosphine (PAMP, the precursor of DiPAMP) with CCl 4 and (-)-menthol in benzene at reflux gave the phosphine oxide ((R)-PAMPO) in good yields and up to 24% ee.Subsequently, we used the more reactive hexachloroaceto...

Reaction of bromoethylsulfonium salt with 1,2-/1,3-aminoalcohols gave six- and seven-membered rings in good-to-excellent yields. The reactions proceed through generation of a vinyl sulfonium salt followed by annulation to give 1,4-heterocyclic compounds such as morpholines and benzoxazepines in a simple procedure. The method accommodates a range of nitrogen substituents and the amino alcohol can be substituted by amino thiols and diamines to give thiomorpholines, piperazines and benzodiazepines.