54322-99-5

-

The TiCl4-catalyzed reaction of α-(phenylseleno)cycloalkanones with aldehydes gives aldol products with high threo selectivity.High stereoselectivity is also achieved in the formation of spiro aldol products starting with α-(phenylseleno)cycloalkanones bearing an aldehyde chain.

Simple diastereoselectivity of several important categories of aldol reactions of persubstituted enolates has been investigated for sterically least biased cyclic and acyclic ketone and aldehyde enolates, 1-4, and has been found to be useful for the stereoselective construction of quaternary carbon centers.The types of reactions examined involve the reaction of lithium, borinate, borate, trialkoxytitanium, trichlorotitanium and zirconium (Cp2ZrCl) enolates, and the reactions of enol silyl ethers under high pressure, fluoride catalysis, and Lewis acid catalysis.In contrast to the less substituted metal enolates, uncatalyzed reactions of persubstituted metal enolates proceeded in a sense anticipated from the conventional Zimmerman-Traxler chair transition state (TS) model.The fluoride-catalyzed reaction of the cyclic enolate 1a showed stereoselectivity consistent with the open extended TS, while enolates 2a-4a showed anomalous behavior.The selectivity of the Lewis acid mediated aldol reaction of enol silyl ethers was found to be dependent on the Lewis acid used, and the BF3*Et2O-mediated reaction of 2a and 3a showed maximum selectivity in a sense predicted by the chair TS.The stereostructures of the aldols have been determined by single-crystal X-ray analysis or by chemical correlations.

A highly convenient two-step sequence for the regiospecific synthesis of cyclic silyl enol ethers has been developed involving the 1,2-addition of dimethyl(phenyl)silyllithium to cyclic α,β-unsaturated ketones followed by the treatment of the resulting silyl carbinols with a catalytic amount of NaH in THF at 25°C.

Reaction of α-halogeno ketones with aldehydes in the presence of CeI3 in tetrahydrofuran is found to give α,β-unsaturated ketones in excellent yields under mild conditions.In contrast, treatment of α-halogeno ketones and carbonyl compounds with CeCl3-NaI or CeCl3-SnCl2 affords β-hydroxy ketones in good yields.It is assumed that these reactions proceed via cerium enolates.The combined reagents, however, cannot be applied to a Reformatsky-type reaction.Regiospecific and aldehyde chemoselective aldol synthesis are also described.

A new aldol reaction effected by the reaction of enol trimethylsilyl ethers and a quarternary ammonium fluoride is reported.Under the influence of a catalytic amount of tetrabutylammonium fluoride at low temperatures, enol silyl ethers react with various aldehydes to give the corresponding aldol trimethylsilyl ethers in fair to good yields.The silyl group of these products can be smoothly removed under mild conditions.Ketones, epoxides, and esters do not serve as electrophiles in this reaction.The reaction proceeds in a regiospecific manner with respect to the enol silyl ethers; the reactions of two regioisomers of 2-methylcyclohexanone with benzaldehyde cleanly give the respective regioisomeric aldol products.The reaction of 4-tert-butyl-1-methyl-2-(trimethylsiloxy)cyclohexene proceeds exclusively by the axial attack of the electrophile, making a strong contrast with the related cases reported on this cyclohexanone system.The aldol addition of a ketone and an aldehyde can be performed without the isolation of the enol silyl ether of the ketone by effecting both the silylation of the ketone and the aldol reaction with the aid of a fluoride anion.The characteristic behavior of the enolate species in this reaction can be rationalized by considering a mobile equilibrium in which the combination of fluorotrimethylsilane and a quarternary ammonium enolate functions as key controlling factor.

A new approach has been demonstrated for the regiospecific aldol synthesis by the simultaneous addition of α-halo carbonyl derivatives and aldehydes or ketones to a suspension of diethylaluminium chloride and zinc in tetrahydrofuran at low temperature.This technique is also employable under mild conditions for the Reformatsky reaction to give β-hydroxy esters in excellent yield.One of the unique synthetic applications of this process is illustrated by the intramolecular cyclization of α-bromo esters of ω-hydroxy aldehyde,which produces macrolides, an important cla ss of compounds in the antibiotic field.