Doubly diastereoselective conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to enantiopure ε-O-protected α,β-unsaturated esters derived from d-ribose

Enantiopure ε-O-silyloxy- and ε-O-benzyloxy-α,β-unsaturated esters derived from d-ribose, each containing a cis-dioxolane unit, display excellent (⩾95:5 dr) levels of diastereofacial directing ability upon conjugate addition of achiral lithium N-benzyl-N-isopropylamide. In contrast to the corresponding enantiopure ε-O-silyloxy-α,β-unsaturated ester derived from l-tartaric acid, which contains a trans-dioxolane unit, the conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to its cis-configured counterpart result in doubly diastereoselective ‘matched’ and ‘mismatched’ reaction pairings in which the inherent reagent control serves to augment or oppose, respectively, the established substrate diastereocontrol.     

Double asymmetric induction as a mechanistic probe: the doubly diastereoselective conjugate addition of enantiopure lithium amides to enantiopure α,β-unsaturated esters and enantiopure α,β-unsaturated hydroxamates

The doubly diastereoselective conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to a range of enantiopure α,β-unsaturated esters [derived from Corey’s 8-phenylmenthol chiral auxiliary] and enantiopure α,β-unsaturated hydroxamates [derived from our ‘chiral Weinreb amide’ auxiliary (S)-N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine] has been used as a mechanistic probe to determine the reactive conformations of these acceptors.     

Stereoselective conjugate additions of sulphoxide stabilised carbanions to α,β-unsaturated esters

The reaction of lithiated alkyl t-butyl sulphoxides with α,β-unsaturated esters gives conjugate addition products in good yield, with high stereoselectivity.     

Selective reduction of α,β-unsaturated esters in the presence of olefins

Several α,β-unsaturated esters containing also isolated olefins or other functionalities subject to saturation were selectively reduced to the corresponding saturated esters by magnesium in methanol.     

Copper-catalyzed conjugate additions of alkylboranes to imidazolyl α,β-unsaturated ketones: formal reductive conjugate addition of terminal alkenes

Conjugate addition of alkylboron compounds (alkyl-9-BBN) to imidazol-2-yl α,β-unsaturated ketones proceeded in the presence of a catalytic amount (10 mol %) of CuCl, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes), and t-BuOK. The alkylboranes are available through alkene hydroboration, and thus the overall process represents a reductive conjugate addition of alkenes to enone derivatives. A variety of functional groups are tolerated in both the alkenes and the α,β-unsaturated ketones. The 2-acylimidazole moiety can easily be converted into the corresponding carboxylic acid, ester, and amide derivatives.     

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.     

Enantioselective organocatalytic conjugate addition of α-nitroacetate to α,β-unsaturated ketones in water

The catalytic enantioselective conjugate addition reaction of α-nitroacetate to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of α-nitroacetate to α,β-unsaturated ketones under aqueous-phase reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are easily converted to chiral δ-keto nitroalkanes and δ-keto esters.     

Addition of alkyllithium and Grignard reagents to tetracarbonyliron complexes of α,β-unsaturated esters

Addition of alkyllithium and Grignard reagents to the tetracarbonyliron complexes of methyl acrylate (1) and methyl crotonate (2) leads to the production of 4-ketoesters via acyl transfer from the metal to the β carbon of the α,β-unsaturated ester.     

Decomposition of benzenediazonium fluoborate in esters of α,β-unsaturated acids

Summary It was shown that In contrast to the Meerwein-Koelsch reaction, the decomposition of benzenediazonlum fluoborate In esters of ,-unsaturated acids proceeds by a heterolytlc mechanism with the phenyl attacking the -carbon and the carbalkoxyl group of these esters. The reaction with ethyl crotonate gave -methylatropic acid (after hydrolysis) and a small amount of a dibasic acid, C₁₄H₁₆O₄ (or C₁₄H₁₄O₄). With methyl acrylate it gave atropic acid, phenyl acrylate, and a smaller amount of -methyl--phenylglutaric acid. With methyl methacrylate It formed benzylacrylic acid and the product of further conversions of phenyl methacrylate, namely the keto phenol 2-methyl-5-hydroxyindan-1-one.     

Organocatalytic conjugate addition of α-nitroacetates to β,γ-unsaturated α-keto esters and subsequent decarboxylation: synthesis of optically active δ-nitro-α-keto esters

Organocatalytic asymmetric conjugate addition of tert-butyl nitroacetates to β,γ-unsaturated α-keto esters has been developed. The subsequent in situ hydrolysis-decarboxylation of the adducts provided 5-nitro-2-oxopentanoates. A pyrrolidine-based thiourea-tertiary amine was identified as the best catalyst. A number of γ-aryl, γ-alkyl, and γ-heteroaryl β,γ-unsaturated α-keto esters and α-substituted tert-butyl nitroacetates were examined in the transformation. Generally 5-nitro-2-oxopentanoates were obtained in good yields (up to 97%) and enantioselectivities (up to 94% ee). The products were readily transformed to chiral proline derivatives by catalytic hydrogenation.     

Iron-catalyzed δ-selective conjugate addition of methyl and cyclopropyl Grignard reagents to α,β,γ,δ-unsaturated esters and amides

Iron-catalyzed δ-selective conjugate addition of methyl and cyclopropyl Grignard reagents to α,β,γ,δ-unsaturated esters and amides took place in good yields to give products exclusively with cis-β,γ-olefinic bond.     

Rhodium-catalyzed conjugate addition of arylindium reagents to α,β-unsaturated carbonyl compounds

A novel rhodium-catalyzed conjugate addition of indium reagents to electron deficient olefins is reported. The reaction takes place in THF/MeOH at 110 °C using arylindium dichlorides, a rhodium(I)-binap complex as catalyst, and α,β-unsaturated ketones and lactones in good yields (45–94%). The addition of MeOH is crucial for an efficient transformation and NMR studies seem to indicate that promotes the catalytic cycle leaving the indium organometallic unaltered. The use of chiral non-racemic ligands allows performing the reaction with moderate enantioselectivities.     

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.     

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.     

An efficient method for the synthesis of enantiopure cis-α,β-epoxy acids

Enantiopure cis-α,β-epoxy acids were prepared via a modified Darzen's reaction employing the titanium-mediated bromination–aldolization of chiral acetate thioimide enolate.     

Synthesis of isoxazolidin-5-ones via stereocontrolled Michael additions of benzylhydroxylamine to l-serine derived α,β-unsaturated esters

The synthesis of optically active isoxazolidin-5-ones from α,β-unsaturated esters is reported. The key features of this synthetic sequence include the stereocontrolled Michael addition of benzylhydroxylamine to alkenes 7 and 8 and the intramolecular cyclization to the target compounds     

Lanthanum-pyBOX complexes as catalysts for the enantioselective conjugate addition of malonate esters to β,γ-unsaturated α-ketimino esters

Abstract

In this paper, we report the application of chiral complexes of La(III) with pyBOX ligands as Lewis acid catalysts in the conjugate addition of malonic esters to N-tosyl imines derived from β,γ-unsaturated α-keto esters to give the corresponding chiral α,β-dehydroamino esters. pyBOX complexes with La(III), Yb(III), Sc(III), and In(III) triflates were assessed in this reaction but only La(III) showed good activity and enantioselectivity, while Yb(III) provided the expected product with low yield and stereoselectivity, and the Sc(III) and In(III) complexes were completely inactive. The complex of La(OTf)₃ with the diphenyl-pyBOX ligand prepared in situ provided the best results and allowed obtaining chiral α,β-dehydroamino esters 3 with excellent yields, E:Z diastereomeric ratios (29:71–99:1) and high enantiomeric excesses (20–95%). The reaction could be applied to imines having a substituted aromatic ring or a heterocycle attached to the double bond, although the presence of electron-withdrawing groups on the aromatic ring was detrimental for stereoselectivity. The reaction products were obtained with the S configuration at the stereogenic center and the Z configuration at the enamine double bond as determined by NOESY experiments and X-ray analysis. Based on the experimental results a stereochemical model involving a nine-coordinate La(III) species has been proposed.     

Double asymmetric induction in the osmylation of -γ-alkoxy-α,β-unsaturated esters

OsO₄ promoted cis-dihydroxylation of enantiomerically pure (E)-α,β- unsaturated esters derived from alkoxyaldehydes occurs with noticeable levels (up to⩾ 45:1) of stereoselection when carried out in the presence of alkaloid derived ligands. Matching and mismatching substrate-ligand pairs have been identified.