Rhodium-catalyzed asymmetric 1,4-addition of arylboron reagents to α,β-unsaturated esters

Reaction of arylboron reagents, arylboronic acids or arylborates, which are readily accessible by lithiation of aryl bromides followed by treatment with trimethoxyborane, with α,β-unsaturated esters in the presence of rhodium/(S)-binap catalyst proceeded with high enantioselectivity to give high yields of optically active β-aryl esters of up to 98% ee. The enantioselectivity depends on the steric bulkiness of the ester moiety.     

NHC–copper-catalyzed asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated ketones

N-Heterocyclic carbene–copper-catalyzed asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated ketones was developed for the synthesis of chiral phosphorus derivatives in high yields with moderate enantioselectivity under mild conditions.     

Rhodium-catalyzed asymmetric 1,4-addition of sodium tetraarylborates to β,β-disubstituted α,β-unsaturated esters

A rhodium-catalyzed 1,4-addition of sodium tetraarylborates to β,β-disubstituted α,β-unsaturated esters has been developed. Highly efficient asymmetric catalysis has also been described to create quaternary carbon stereocenters at the β-position of esters by tuning the ester group of substrates and employing a readily available chiral diene ligand.     

Palladium-catalyzed 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles

Highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles catalyzed by a PCP pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (91-99% ee) under mild conditions. The products obtained can be further converted into chiral phosphine-oxazoline ligands.     

Palladium-catalyzed 1,4-addition of diarylphosphines to α,β-unsaturated aldehydes

A highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated aldehydes catalyzed by a bis(phosphine) pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 98% ee) under mild conditions. The application of the current method to the synthesis of enantiopure bisphosphine and its pincer-Pd complex has also been demonstrated.     

Addition of esters of nitroacetic acid to α,β-unsaturated ketones

Summary The addition reaction of esters of nitroacetic acid to, -unsaturated ketones was studied, and new esters of ketonitroacids were prepared.     

Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated ketones with DIFLUORPHOS and SYNPHOS analogues

Applications of electron-deficient DIFLUORPHOS and SYNPHOS analogues in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to α,β-unsaturated ketones afford the 1,4-addition adducts in yields up to 92% and with 99% ee. Particularly, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to nonsubstituted maleimide substrates using the (R)-3,5-diCF(3)-SYNPHOS ligand is also reported. This protocol provides access to various enantioenriched 3-substituted succinimide units of biological interest, in high yields and good to excellent ee up to 93%, which could be upgraded up to 99% ee, after a single crystallization.     

Enantioselective 1,4-addition of aryllithium reagents to α,β-unsaturated tert-butyl esters in the presence of chiral additives

Reaction of t-BuLi with a mixture of aryl bromide and chiral diamine, amino ether or diether, in toluene at −78°C provided chiral aryllithium complexes efficiently. Reaction of these aryllithium complexes with α,β-unsaturated tert-butyl esters afforded the 1,4-addition products in up to 88% ee.     

Iodine-catalyzed 1,4-addition of 2-(trimethylsilyloxy)furan to α,β-unsaturated ketones: a facile synthesis of γ-butenolides

The α,β-unsaturated compounds undergo smooth conjugate addition with 2-(trimethylsilyloxy)furan (TMSF) in the presence of 10 mol % of iodine under mild and neutral conditions to afford the corresponding γ-substituted butenolides in high yields and with good diastereoselectivity. The use of iodine makes this procedure simple, convenient and cost effective.     

The Darzens condensation of α,β-unsaturated aldehydes and ketones

The one-pot Darzens condensation of α,β-unsaturated aldehydes and ketones with enolates of an α-bromo ester or ketone is described.     

Copper(I) catalyzed asymmetric 1,2-addition of Grignard reagents to α-methyl substituted α,β-unsaturated ketones

The first catalytic enantioselective 1,2-addition of Grignard reagents to ketones is presented. This additive-free copper(I) catalyzed 1,2-addition provides chiral allylic tertiary alcohols with an er of up to 98:2 and excellent yields due to the complete shift of overwhelming 1,4-selectivity of copper(I)-catalysts towards 1,2-selectivity in the addition reaction to enones.     

Asymmetric 1,4-addition of organoboronic acids to α,β-unsaturated ketones and 1,2-addition to aldehydes catalyzed by a palladium complex with a ferrocene-based phosphine ligand

A combination of palladium with ferrocene-based phosphine ligand with a carbon–bromine bond was found to be a good catalyst for the 1,4-addition of arylboronic acids to α,β-unsaturated ketones and the 1,2-addition to aldehydes. Using Pd(dba)₂ and (S,R_p)-[1-(2-bromoferrocenyl)ethyl]diphenylphosphine (S,R_p)-1, 3-phenylcyclohexanone was obtained from the reaction of 2-cyclohexen-1-one with phenylboronic acid in the presence of K₂CO₃ in toluene at room temperature after 3 h in 92% yield with 76% ee. In the 1,2-addition of 4-methylphenylboronic acid to benzaldehyde, 96% of (4-methylphenyl)phenylmethanol was afforded after 24 h, while the enantiomeric excess was only 6%.     

Modular approach to saturated and α,β-unsaturated ketones

2-Fluoro-6-pyridinyloxy derivatives of 2-ethoxyvinyl carbinols react with radicals derived from xanthates by an addition-fragmentation pathway to give highly functionalized ketones after acid hydrolysis. 1,4-Diketones are readily accessible by this approach. α,β-Unsaturated ketones can be obtained by starting with geminal acetoxy xanthates prepared by addition of a simpler xanthate to vinyl acetate.     

Two-carbon homologation of aldehydes and ketones to α,β-unsaturated aldehydes

Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,β-unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.     

Sc(III)-catalyzed enantioselective addition of thiols to α,β-unsaturated ketones in neutral water

This report concerns Lewis acid catalyzed enantioselective sulfa-Michael addition in neutral water by using a very efficient Sc(OTf)(3)/bipyridine 1 catalytic system. It is noteworthy that the protocol presented employs water as a reaction medium and allows us to obtain very high stereoselectivity and satisfactory yields for β-keto sulphides deriving from aliphatic thiols. The recovery and reuse of both the aqueous medium and the catalytic system is also reported.     

Synthesis of β-carbolines from aldehydes and ketones via the α-siloxy α,β-unsaturated esters

We report an efficient method for the synthesis of β-carbolines from α-siloxy α,β-unsaturated esters, which are accessible from a variety of aldehydes and ketones.     

Copper-catalyzed enantioselective 1,4-conjugate addition of dialkylzinc reagents to α,β- and α,β,γ,δ-unsaturated ketones

An enantioselective Cu(II)-catalyzed conjugate addition of dialkylzinc reagents to α,β- or α,β,γ,δ-unsaturated ketones with chiral cyclohexane-based amidophosphine ligands was developed. With 2 mol% of Cu(OAc)₂·H₂O/L5, the conjugate addition of diethylzinc to α,β-unsaturated ketones was achieved in good-to-excellent yields (up to 98%) and high enantioselectivities (up to 92% ee). This catalytic system was shown to be efficient for the 1,4-conjugate addition of Et₂Zn to (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one with 85% yield and 90% ee. Moreover, with 1 mol% of Cu(OTf)₂/L11, the conjugate addition of α,β,γ,δ-unsaturated ketones was accomplished with 1,4-regioselectivity, good yields (79–86%) and excellent enantioselectivities (up to 97% ee).     

Cobalt-catalyzed conjugate addition of silylacetylenes to α,β-unsaturated ketones

Catalytic addition of silylacetylenes to α,β-unsaturated ketones proceeded in the presence of a cobalt complex coordinated with a bisphosphine ligand to give high yields of β-alkynylketones.     

DABCO catalyzed dimerization of α,β-unsaturated ketones and nitriles

α,β-Unsaturated ketones dimerize in the presence of catalytic amount of 1,4-diazabicyclo[2.2.2]octane(DABCO) to produce the corresponding 2-methylene-1,5-diketones in good yields. Acrylonitrile provides the corresponding dimerized product.     

Iron-catalyzed decarboxylative methylation of α,β-unsaturated acids under ligand-free conditions

It is the first time to find that iron-catalyzed decarboxylative methylation of α,β-unsaturated acids could be performed in the absence of any ligands. During the reaction, the configuration of the double bond could be retained. It is noteworthy that di-tert-butyl peroxide (DTBP) was employed not only as the oxidant, but also as the methyl source.