Electroreductive acylation of aromatic ketones with acylimidazoles.

[Reaction: see text]. The intermolecular reductive coupling of aromatic ketones with acylimidazoles was effected by electroreduction in the presence of chlorotrimethylsilane and gave alpha-trimethylsiloxy ketones and esters. The best result was obtained using Bu4NPF6 as a supporting electrolyte and a Pb cathode in THF. The alpha-trimethylsiloxy-containing products were transformed to the corresponding alpha-hydroxy ketones and esters by treatment with TBAF in THF. This method was also effective for the intramolecular reductive coupling of delta- and epsilon-keto acylimidazoles.

Electroreductive intramolecular coupling of aromatic beta- and gamma-imino esters: a new synthetic method for N-alkoxycarbonyl-2-aryl-3-ones and cis-2-aryl-3-ols of pyrrolidines and piperidines.

The electroreduction of aromatic beta- and gamma-imino esters prepared from beta-alanine and GABA in the presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave mixed ketals of N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones, respectively. The best result of the electroreductive intramolecular coupling was achieved using Bu(4)NClO(4) as a supporting electrolyte and a Pb cathode in THF. Acid hydrolysis of the mixed ketals afforded N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones in good yields. The reduction of these ketones with NaBH(4) in methanol afforded the corresponding N-alkoxycarbonyl-cis-2-arylpyrrolidin-3-ols and cis-2-arylpiperidin-3-ols diastereospecifically.

Diastereoselective dl-hydrocoupling of benzalacetones by electroreduction.

Electroreduction of benzalacetones with an undivided cell in Et(4)NOTs/acetonitrile gave cyclized dl-hydrodimers as mixtures of two diastereomers. The hydrodimerization proceeded stereoselectively to afford linear dl-hydrodimers, and the following cyclization led to two thermodynamically stable diasteromers of cyclopentanols.

Electroreductive intramolecular coupling of chiral alpha-imino esters: stereoselective synthesis of mixed ketals of cis-2,4-disubstituted azetidine-3-ones.

The electroreduction of chiral aromatic alpha-imino esters prepared from (S)-alpha-amino acids, such as (S)-valine, (S)-leucine, and (S)-phenylalanine, in the presence of chlorotrimethylsilane and triethylamine afforded four-membered cyclized products, mixed ketals of cis-2,4-disubstituted azetidine-3-ones, stereospecifically (>99% de, 85-99% ee). The best result of the electroreductive cyclization was obtained using Bu(4)NClO(4) as a supporting electrolyte and a Pt cathode. The absolute stereochemistry of the obtained single stereoisomers was confirmed to be 2R,3R,4S by X-ray crystallography. Calculations for the transition states of the cyclization support the stereospecific formation of the (2R,3R,4S)-isomers.

Stereoselective hydrocoupling of cinnamic acid esters by electroreduction: application to asymmetric synthesis of hydrodimers.

The electroreduction of Ar-substituted methyl cinnamates in acetonitrile gave all-trans cyclized hydrodimers stereoselectively (58 approximately 90% de). In all cases, small amounts (<10% yield) of meso hydrodimers were also formed. The electrolysis was performed conveniently using an undivided cell at a constant current. The transition states for the hydrocoupling were calculated with semiempirical methods. The all-trans cyclized hydrodimers were transformed to C(2)-symmetric dl-3,4-diaryladipic acids and trans-3,4-diarylcyclopentanones. The chiral auxiliary [(1R)-exo]-3-exo-(diphenylmethyl)borneol, prepared from (1R)-(+)-camphor, was highly effective for the stereoselective hydrocoupling of its cinnamates by electroreduction. From the resulting hydrodimers, (3R,4R)-3,4-diaryladipic acid esters and (3R,4R)-3,4-diarylhexane-1,6-diols were synthesized in 87-95% ee.