With regard to atom economy and E-factor, catalytic condensation of carboxylic acids with equimolar amounts of alcohols is the most desirable. Although several highly active dehydration catalysts have been reported, more efficient alternatives are still strongly needed because the dehydrative esterification of tertiary alcohols, phenols, acid-sensitive alcohols, amino acids, and hardly soluble alcohols has never proceeded satisfactorily. Here we report new insights into the classical DMAP-catalyzed acylation of alcohols: surprisingly, only a 0.05-2 mol % of DMAP can efficiently promote acylation of alcohols with acid anhydrides under auxiliary base- and solvent-free conditions to give the corresponding esters in high yields. Furthermore, we achieved the recovery and reuse of commercially available polystyrene-supported DMAP without using any solvents. These serendipitous findings provide widely useful and environmentally benign esterification methods, which might be more practical and reliable than catalytic dehydrative condensation methods, in particular, for the less reactive alcohols which hardly condense with carboxylic acid directly.

The asymmetric epoxidation of allylic alcohols by metal catalysts, [1] though a widely used synthetic method, could gain even more practical applications if the following were realized: 1) employment of a ligand designed to achieve high enantioselectivity for Z olefins, 2) catalyst loading of less than 1 mol %, 3) reaction temperatures of 0 8C to room temperature over a shorter time, 4) use of aqueous tert-butyl hydroperoxide (TBHP) as an achiral oxidant instead of anhydrous TBHP, and 5) simple workup procedures for small epoxy alcohols. Many important improvements have been made to the methodology developed by Sharpless and co-workers for the titanium tartarate catalyzed asymmetric epoxidation. [2][3][4] Nonetheless, each of these approaches fails to fulfil the above criteria.[1-5] Herein, we report our recent progress on all five fronts.Recently, we developed a series of hydroxamic acid ligands and demonstrated that they were effective for the vanadium-catalyzed asymmetric epoxidation of allylic alcohols. [6,7] These results suggested that several structural features of the hydroxamic acid significantly enhanced the rate and enantioselectivity of the reaction. However, the ligand deceleration effect was still observed in these cases. [6][7][8] To exclude this effect, we planned to design a new C 2 -symmetric bishydroxamic acid 1 that incorporated the following features: 1) an additional binding site with which 1 can chelate as a bidentate ligand to the metal center to complete the generation of a chiral vanadium/ligand complex more efficiently than the monohydroxamic acid and 2) an R group of the amide in 1 that is sufficiently large so the oxygen atom of the carbonyl group is directed towards the cyclohexane ring to minimize steric interaction and restrict its coordination with the metal center. Furthermore, the attachment of additional ligands to the vanadium center will also be restricted because of steric reasons. Thus, doubly or triply coordinated species, which are believed to be inactive, should not be generated from the bishydroxamic acid ligand, and consequently a ligand deceleration effect within the vanadium/1 catalytic system should not be problematic. [8] We devised a synthetic protocol for 1 from a readily available diamine tartrate salt (Scheme 1) so that the veracity of our hypothesis could be proved.[9] These reaction sequences can be carried out with satisfactory yields and without any purification to provide 4, from which we have prepared an array of diverse ligands 1 a-c.As expected, the use of a complex of vanadium with ligand 1 provided epoxy alcohols both in good yields with high enantioselectivities (Table 1).[9] The catalyst 5 a, derived from vanadium and 1 a, invariably induced excellent enantioselectivities during the epoxidation of trans-disubstituted and -trisubstituted allylic alcohols. The most gratifying aspect of this catalytic system was the excellent enantioselectivity observed during the epoxidation of cis-substituted allylic alcohols with catalyst 5 b, which was derived from...

This communication describes the rational design of an l-histidine-derived minimal artificial acylase. Our new artificial acylase, tert-butyldiphenylsilyl ether of N-(2,4,6-triisopropylbenzenesulfonyl)-pi(Me)-l-histidinol, is a simple and small molecule (molecular weight = 660) that contains only one chiral carbon center that originates from natural l-histidine. The kinetic acylation of racemic secondary alcohols induced by this compound showed an S (kfast/kslow) value of up to 93. A reusable polystyrene-bound artificial acylase was also developed to examine its practical usability.

The exothermic reaction of 3,5-bis(trifluoromethyl)phenyl or 4-nitrophenyl isothiocyanate with 4-pyrrolidinopyridine (PPY) gave the corresponding arylaminothiocarbonylpyridinium salts in quantitative yields. These novel zwitterionic salts were effective as organocatalysts for the transesterification reaction of an equimolar mixture of methyl carboxylates and alcohols in hydrocarbons such as heptane and octane under azeotropic reflux conditions with the removal of methanol. In sharp contrast, PPY was inert as a catalyst under the same reaction conditions.