Stereodivergent total asymmetric synthesis of polyhydroxylated pyrrolidines via tandem allylic epoxidation and intramolecular cyclization reactions

Epoxidation of the allylic alcohols 10 and 11 using the VO(acac)₂/t-BuOOH system followed by an intramolecular 5-exo cyclization of the resulting δ-epoxycarbamates 12, 13, 18, and 19 has been shown to provide a general and efficient solution for the asymmetric synthesis of polyhydroxy pyrrolidines. The requisite vicinal amino alcohol functionality was enantio-/regio-selectively installed by the Os-catalyzed asymmetric aminohydroxylation reaction of the designed achiral olefin 6.     

Galerkin Projections and Finite Elements for Fractional Order Derivatives

Ordinary differential equations (ODEs) with fractional order derivatives are infinite dimensional systems and nonlocal in time: the history of the state variable is needed to calculate the instantaneous rate of change. This nonlocal nature leads to expensive long-time computations (O(t ²) computations for solution up to time t). A finite dimensional approximation of the fractional order derivative can alleviate this problem. We present one such approximation using a Galerkin projection. The original infinite dimensional system is replaced with an equivalent infinite dimensional system involving a partial differential equation (PDE). The Galerkin projection reduces the PDE to a finite system of ODEs. These ODEs can be solved cheaply (O(t) computations). The shape functions used for the Galerkin projection are important, and given attention. The approximation obtained is specific to the fractional order of the derivative; but can be used in any system with a derivative of that order. Calculations with both global shape functions as well as finite elements are presented. The discretization strategy is improved in a few steps until, finally, very good performance is obtained over a user-specifiable frequency range (not including zero). In particular, numerical examples are presented showing good performance for frequencies varying over more than 7 orders of magnitude. For any discretization held fixed, however, errors will be significant at sufficiently low or high frequencies. We discuss why such asymptotics may not significantly impact the engineering utility of the method.     

Development of more potent 4-dimethylaminopyridine analogues

[reaction: see text] The syntheses of bicyclic diaminopyridines 3 and 4 and tricyclic triaminopyridines 5 and 6, two novel series of nucleophilic catalysts, are described. Arguments are made for predicting the superiority of these catalysts over DMAP and even 2, the best esterification catalyst reported to date. The efficiencies of DMAP, PPY, and 2-6 in catalyzing the esterification of tertiary alcohols were compared. As predicted, 5 and 6 were about 6-fold more effective than DMAP and slightly better than 2.     

Chemoenzymatic synthesis of optically active heterocyclic homoallylic and homopropargylic alcohols

A chemoenzymatic methodology has been developed using indium-mediated allylation of heterocyclic aldehydes under aqueous conditions followed by Pseudomonas cepacia lipase-catalyzed enantioselective acylation of racemic homoallylic and homopropargylic alcohols in organic media. It is observed that the lipase immobilized on ceramic particles (PS-C Amano II) catalyzes the resolution in a highly enantioselective manner in less time as compared to the native enzyme (PS Amano). The approach provides new functionalized chiral synthons useful in the synthesis of natural and pseudonatural products.     

Asymmetric synthesis of (+)-iso-6-cassine via stereoselective intramolecular amidomercuration

The first asymmetric synthesis of (+)-iso-6-cassine is described. Lipase-catalyzed resolution, enantioselective Overman rearrangement, and diastereoselective intramolecular amidomercuration were used for the installation of the three stereocenters in (+)-iso-6-cassine, and cross-metathesis was employed for the attachment of the side-chain.     

Conformationally restricted 4-dimethylaminopyridine (DMAP) analogs: synthesis and evaluation of catalytic effectiveness

The syntheses of a series of conformationally restricted 4-dimethylaminopyridine (DMAP) analogs 1-3 are described. Evaluations of catalyst effectiveness demonstrated that 1 was the best catalyst for the acetylation reaction of a tertiary alcohol, while 2 and 3 were roughly comparable to DMAP. The order of effectiveness of these catalysts roughly parallels their acetylation enthalpies estimated from ab initio calculations.