ABSTRACT
Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of "classic" natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge.
ABSTRACT
The palladium-catalyzed decarboxylative allylic alkylation of diastereomeric ß-ketoesters derived from 4-tert-butylcyclohexanone is described. These experiments were performed to elucidate our understanding of stereoablative enantioconvergent catalysis. A detailed analysis of the product distribution, including stereochemical outcome of the products, is included. These studies also reveal an interesting example of selectivity that is governed by competing modes of substrate and catalyst control.
ABSTRACT
The development of (trimethylsilyl)ethyl ester protected enolates is reported. The application of this class of compounds in palladium-catalyzed asymmetric allylic alkylation is explored, yielding a variety of α-quaternary six- and seven-membered ketones and lactams. Independent coupling partner synthesis engenders enhanced allyl substrate scope relative to traditional ß-ketoester substrates; highly functionalized α-quaternary ketones generated by the union of (trimethylsilyl)ethyl ß-ketoesters and sensitive allylic alkylation coupling partners serve to demonstrate the utility of this method for complex fragment coupling.
Subject(s)
Allyl Compounds/chemistry , Palladium/chemistry , Trimethylsilyl Compounds/chemistry , Trimethylsilyl Compounds/chemical synthesis , Alkylation , Esters , Molecular Structure , StereoisomerismABSTRACT
The first regio-, diastereo-, and enantioselective allylic alkylation of acyclic ß-ketoesters to form vicinal tertiary and all-carbon quaternary stereocenters is reported. Critical to the successful development of this method was the employment of iridium catalysis in concert with N-aryl-phosphoramidite ligands. Broad functional group tolerance is observed at the keto-, ester-, and α-positions of the nucleophile. Various transformations demonstrating the utility of this method for rapidly accessing complex enantioenriched compounds are reported.
Subject(s)
Acrylates/chemistry , Allyl Compounds/chemical synthesis , Esters/chemistry , Iridium/chemistry , Ketones/chemistry , Organometallic Compounds/chemistry , Alkylation , Allyl Compounds/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
Highly congested vicinal stereocenters comprised of tertiary and all-carbon quaternary centers were generated via Ir-catalyzed asymmetric allylic alkylation of ß-ketoesters. These catalytic reactions proceed in excellent yields with a broad scope on either reaction partner and with outstanding regio-, diastereo-, and enantiocontrol. Implementation of a subsequent Pd-catalyzed alkylation affords dialkylated products with pinpoint stereochemical control of both chiral centers.
