An organocatalytic method for the chemo- and regioselective acylation of monosaccharides has been developed. Treatment of octyl beta-D-glucopyranoside with isobutyric anhydride in the presence of 10 mol % of a C2-symmetric chiral 4-pyrrolidinopyridine catalyst (1) at -50 degrees C gave the 4-O-isobutyryl derivative as the sole product in 98% yield. Thus, chemoselective acylation, favoring a secondary hydroxyl group in the presence of a free primary hydroxyl group, and regioselective acylation, favoring one of three secondary hydroxyl groups, took place with perfect selectivity. A competitive acylation between octyl beta-D-glucopyranoside and a primary alcohol (2-phenylethanol) with 1.1 equiv of isobutyric anhydride in the presence of 1 gave the 4-O-isobutyrate of octyl beta-D-glucopyranoside with 99% regioselectivity in 98% yield, which indicates that acylation of the secondary hydroxyl group at C(4) of the carbohydrate proceeds in an accelerative manner. A possible mechanism, involving multiple hydrogen-bonding between 1 and the monosaccharide, is proposed for the chemo- and regioselective acylation.

The epimerization-free formation of peptide bonds is crucial for the development of peptide therapeutics and pharmaceuticals. Herein, we report a hydrosilane-mediated approach for the construction of peptide bonds between most amino acids under ambient conditions. This concise protocol with an original silylating reagent HSi(OCH(CF 3 ) 2 ) 3 facilitates the use of amino acids bearing a broad variety of functional groups without any epimerization. Moreover, a catalytic system using an aminosilane catalyst enables not only the acceleration in silylation of carboxylic acids but also amide synthesis with minimal substrate use (electrophile/nucleophile/silylating reagent = 1:1:1) and waste production (hydrogen gas and a siloxane). These simple and powerful approaches are established as a potentially general paradigm in synthesis of desired peptides in high yields.

The 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated sp(3) C-H bond arylation of tetrahydroisoquinolines and isochromans is described. The corresponding products were facilely synthesized via a simple nucleophilic addition reaction between readily available aryl Grignard reagents and iminium (or oxonium) cations generated in situ by DDQ oxidation of tetrahydroisoquinolines (or isochromans) under mild conditions.

Nonprotected carbohydrates: The catalytic regioselective thiocarbonylation of carbohydrates by using organotin dichloride under mild conditions was demonstrated. The reaction afforded various deoxy saccharides in high yields and excellent regioselectivity in a minimum number of steps. The regioselectivity of the thiocarbonylation is attributed to the intrinsic character of the carbohydrates based on the stereorelationship of their hydroxy groups (see scheme).