Eugene Ghera

Stereoselective and enantioselective synthesis of five-membered rings via conjugate additions of allylsulfone carbanions*

This lecture describes some of our studies of lithio derivatives of allyl sulfone carbanions which add α-regioselectively as well as anti diastereoselectively to Michael acceptor olefins. This can be ascribed to chelation in the Michael addition step. When the reaction leads to subsequent ring closure by using a bromoallyl sulfone, the latter acts as a methylenemethane synthon in a (3+2) Michael-initiated ring closure, affording highly functionalized cyclopentane derivatives. Such additions proceed with high stereoselectivity and with asymmetric induction leading to nonracemic substituted cyclopentanones. Additions of allyl sulfone carbanions also proceed stereoselectively to C=N systems containing a chiral auxiliary on N. These can be used in the synthesis of optically active five- and six-membered ring N-heterocycles. Furthermore, chiral groups on the allyl sulfone moiety can induce significant remote asymmetric induction, made possible by the presence of an aromatic π-system which promotes intramolecular chelation to the Li cation.

A new diastereoselective 3+2 annulation approach to five-membered carbocycles.☆

The newly prepared 1-bromo-2-methylene-3-phenylsulfonylpropane 2 reacts with α,β unsaturated esters in a Michael induced ring closure to provide cyclopentane derivatives with complete diastereoselectivity.

Asymmetric synthesis of substituted cyclopentanes via Michael initiated ring closure reactions

Abstract Michael initiated ring closure reactions of bromosulfone 1 and γ-oxygenated (E)-α,β-unsaturated esters, which lead stereohomogeneously to trisubstituted methylenecylopentanes, proceed also with good facial selectivity. The use of nonracemic enoate 1 4 in these reactions led to the synethesis of enantiomerically pure cylcopentanone 1 7 . The reason for the preferred anti -selective. Michael addition of enoate 1 4 with allyl and alkyl α-phenylsulfonyl lithiated reagents is discussed.

Reductive transformations with trimethylsilyl chloride-sodium iodide. A new synthesis of 4H-1,3-oxazines☆

Abstract 1-Arylalkenes and 1-arylalkanols are reduced to arylalkanes on heating with trimethylsilyl chloride/sodium iodide in CH 3 CN. Under similar conditions enones, dialkylated in the β-position of the double bond, give 4H-1,3-oxazines.

Intermolecular [3+2] MIRC reactions with alkynoates. Asymmetric Michael addition leading to a nonracemic cyclopentene-annulated α,β-butenolide

Abstract A novel Michael-initiated ring closure reaction involving allylic chlorosulfone ( 2 ) and γ-alkoxy-α,β-ynoates to afford 4-methylenecyclopentenecarboxylates is reported, while with γ-alkylynoates no reaction occurred. With chiral phenyl ynoates 4 , the reaction proceeds by 1,3-asymmetric induction and leads further to a nonracemic annulated α,β-butenolide ( 7 ).

Facile construction of substituted bicyclo [n.3.1] alkanones and the synthesis of a 12-membered dilactone via a new functionalized pentadienoic ester

Abstract 4-Hydroxymethyl-2,4-pentadienoate was effectively synthesized and used for a synthetic entry to keto bridged bicyclo [n.3.1] alkanones and for the synthesis of a 12-membered macrodilide characterized by two trans double bonds, part of two vinylogous α-methylene lactone units.

Michael reactions of allylic sulfones with nitroolefins. Regio- and stereochemical control

Michael addition of allylsulfone carbanions to nitroolefins where shown to be sensitive to substitution in both the donor and the acceptor. While sulfone 10 gave predominantly products of γ-addition with aromatic nitroolefins, addition to aliphatic nitroolefins produced almost exclusively α-adducts. In the presence of an OH function in the sulfone (see 13) only (Z) γ-adducts were observed, while a bromine substituent reversed the regiochemistry.