Herein is reported the development of a new process to manufacture (S)-pregabalin. The method comprises six steps, run under the catalysis of a recyclable polymer bound phase transfer catalyst, and afforded (S)-pregabalin in overall 54% yield, starting from building blocks acetylacetone, isovaleraldehyde, and nitromethane.
Abstract:Heavily substituted cyclopropane esters were prepared in high yields, complete diastereoselection and average (up to 58%) enantioselectivity. The reaction described herein entailed reacting 4-nitro-5-bromostyrylisoxazoles, a class of powerful Michael acceptors with malonate esters under the catalysis of 5 mol% of a chincona derived phase-transfer catalyst.
Herein we report a two-step sequence for the preparation of amides starting from azides and enolisable aldehydes. The reaction proceeded via the formation of triazoline intermediates that were converted into amides via Lewis acid catalysis. Preliminary studies on the preparation of triazolines under chiral phase transfer catalysis are also presented, demonstrating that enantioenriched amides could be prepared from achiral aldehydes in moderate to low enantioselectivity.
An
enantioselective protocol for the desymmetrization of cis-3,5-O-arylidenecyclohexanones has been
developed that proceeded under the catalysis of readily available
and inexpensive Cinchona-derived quaternary ammonium
salts. The synthetic relevance of the methodology was exemplified
by the synthesis of a key intermediate that could be used in the preparation
of the active pharmaceutical ingredient, paricalcitol (Zemplar).
Herein we report the first organocatalytic method for the desymmetrization of meso-aziridines that does not require the use of an external nucleophilic reagent. The process was designed upon a base promoted rearrangement of bicyclic meso-cyclopentanone aziridines, that progresses in intramolecular fashion to provide densely functionalized cyclic ketones, key intermediates for the preparation of Active Pharmaceutical Ingredients. The key enantio-determining step proceeded under the catalysis of a bifunctional thiourea organocatalyst. The process provides an entry to a class of highly functionalized chiral amines, 4-aminocyclopentenones, not accessible with previous desymmetrization methods. The ambiphilic nature of the products makes them versatile synthetic intermediates in the preparation of natural products and popular antiviral nucleoside inhibitors, for example abacavir.
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