Aldol reaction of butane-2,3-diacetal protected methyl glycerate

The addition of aldehydes to butane-2,3-diacetal protected glycerates has been investigated. The reaction was shown to be diastereoselective by ¹H NMR spectroscopy thus confirming the ability of the diacetal to influence the stereochemical outcome of the new stereogenic center, the configuration of which was determined by Mosher’s ester analysis.     

Michael, Michael-aldol and Michael-Michael reactions of enolate equivalents of butane-2,3-diacetal protected glycolic acid derivatives

Consecutive coupling reactions of butane-2,3-diacetal protected glycolic acid derivatives with Michael acceptors and aldehydes are reported. An enantiopure sample of this building block was used to kinetically resolve a chiral Michael acceptor present as a racemic mixture of enantiomers.     

Studies on the generation of enolate anions from butane-2,3-diacetal protected glycolic acid derivatives and subsequent highly diastereoselective coupling reactions with aldehydes and acid chlorides

Highly diastereoselective coupling reactions of enolates derived from butane-2,3-diacetal protected glycolic acids 1 and 2 and their alkylated derivatives with aldehydes are reported together with their efficient acid-catalysed deprotection to yield enantiopure anti-2,3-dihydroxyesters. A procedure to provide the corresponding syn-2,3-dihydroxyesters is also described in two cases, proceeding via an acylation-reduction sequence. An usual double addition reaction of butane-2,3-diacetal protected glycolic acid to small aliphatic acid chlorides provides a synthetically useful, densely-functionalised lactone after acidic deprotection.     

Diastereoselective diallylation of various butane-2,3-diacetals by allylsilane

Five butane-2,3-diacetals obtained from the reaction of 1,2-diols and methanol with biacetyl have been treated with allylsilane in the presence of titanium tetrachloride to afford bis-allyldioxanes as single diastereoisomers.     

Diastereoselective reductive aldol reactions of Boc-protected electron deficient pyrroles

An anti-selective reductive aldol reaction of a Boc-protected, 2-substituted pyrrole is reported. Reduction with LiDBB generates an exocyclic lithium enolate, but optimal stereoselectivity is obtained by transmetallation to magnesium with MgBr₂·OEt₂. The corresponding syn-aldols can easily be obtained (protected as carbamates) by subsequent inversion.     

Mimicking aldolases through organocatalysis: syn-selective aldol reactions with protected dihydroxyacetone

A practical organocatalytic strategy designed to mimic the l-rhamnulose 1-phosphate and D-fructose 1,6-diphosphate aldolases has been developed and shown to be effective in the preparation of carbohydrates and polyol derivatives. Threonine-based catalysts facilitated the aldol reaction of protected dihydroxyacetone or protected hydroxacetone with a variety of aldehydes to provide syn-aldol products with good yields and ee's up to 98%.     

Diastereoselective intermolecular cobalt-catalyzed reductive aldol reactions of alpha,beta-unsaturated amides with ketones

Under cobalt catalysis, diethylzinc mediates the conjugate reduction of alpha,beta-unsaturated amides to produce ethylzinc enolates that react with ketones in situ to produce tertiary alcohol-containing aldol products with up to >19:1 diastereoselectivity.     

Preparation of enantiopure butane-2,3-diacetals of glycolic acid and alkylation reactions leading to alpha-hydroxyacid and amide derivatives

The preparation of butane-2,3-diacetal protected glycolic acid and related systems is described together with highly selective alkylation reactions of (R,R) and (S,S) butanediacetal protected glycolic acid. These compounds are readily deprotected to give enantiopure alpha-hydroxyacids, alpha-hydroxyesters or alpha-hydroxyamides by suitable choice of conditions.     

Asymmetric direct aldol reactions of pyruvic derivatives

Simple chiral primary-tertiary diamine-Br?nsted acid conjugates such as 1e can effectively catalyze the direct aldol reactions of pyruvic derivatives with excellent syn diastereoselectivities and enantioselectivities, thus functionally mimicking the pyruvate-dependent type I aldolases.     

Diastereoselective aldol reactions of enolates generated from vicinally substituted trimethylsilylmethyl cyclopropyl ketones

[reaction: see text] Vicinally substituted trimethylsilylmethyl cyclopropyl ketones undergo facile desilylative ring opening with Lewis acids under mild conditions. The enolates, thus generated, undergo aldol addition with aldehydes and ketones. The diastereoselectivity of the reaction with aldehydes depends on the nature of the Lewis acid used. The resulting aldol product is easily converted into a substituted tetrahydrofuran derivative.     

Diastereoselective aldol condensations of tin enolates with aldehydes

The reaction of tin enolates of cyclohexanone or propiophenone with benzaldehyde at ?78°C gives predominately the $\text{threo}$ aldol diastereomer.     

Asymmetric aldol reactions catalyzed by new spiro diamine derivatives

Two new organocatalysts derived from l-proline and a novel chiral spiro diamine bearing a C₂ symmetric backbone, were introduced for an asymmetric aldol reaction in moderate to good asymmetric induction in up to 76% ee and high yields.     

Cycloaddition reactions with 2,3‐benzodiazepine derivatives

We report here on some 3+2 dipolar cycloaddition reactions of propargyl, allyl and cyano substituted 2,3‐benzodiazepines with in situ generated nitrile oxides and diazomethane. The reactivity of carbon‐nitrogen double bonds of the 5H‐[2,3]benzodiazepine ring system was also noticed.     

Diastereoselective cobalt-catalyzed alkylative aldol cyclizations using trialkylaluminum reagents

Co(acac)2.2H2O serves as an effective precatalyst for alkylative aldol cyclizations of alpha,beta-unsaturated amides with ketones using trialkylaluminum reagents. These reactions provide beta-hydroxylactams containing three contiguous stereocenters with high levels of diastereoselection.     

Diastereoselective protocols for the synthesis of 2,3-trans- and 2,3-cis-6-methoxy-morpholine-2-carboxylic acid derivatives

Two diastereoselective and straightforward protocols for the high-yielding synthesis of 2,3-trans- and 2,3-cis-6-methoxy-3-substituted morpholine-2-carboxylic esters were realized in few steps, through the condensation between 5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-one and an appropriate imine, which is the key reaction to control the C2-C3 relative stereochemistry, followed by a methanolysis/ring-closure tandem reaction sequence. In particular, 2,3-trans-morpholines derive from the R*,S*-product of the acid condensation of N-functionalized alkylimines with the silylketene acetal of the above lactone, whereas 2,3-cis-morpholines derive from the R*,R*-product of basic condensation of an N-tosylimines with the lactone.     

Diastereoselective synthesis of enantiomeric tertiary alcohols via nucleophilic additions to protected D- and L-erythrulose derivatives

The diastereoselectivity of the addition of several organometallic reagents to the carbonyl group of protected - and -erythrulose derivatives has been investigated. Tertiary alcohols are stereoselectively formed, the diastereomeric ratio being markedly dependent on the reagent type, solvent and temperature.     

N-Prolinylanthranilic acid derivatives as bifunctional organocatalysts for asymmetric aldol reactions

Several N-prolinylanthranilic acid derivatives were prepared and tested as bifunctional organocatalysts in the direct asymmetric aldol reaction of cyclohexanone with p-nitrobenzaldehyde. It was found that methyl substitution ortho to the carboxylic acid improves enantioselectivity, but substitution ortho to the anilide group does not. The catalyst derived from 2-amino-6-methylbenzoic acid was tested over a range of direct asymmetric aldol reactions and its overall performance is equal to or better than many of the known prolinamide catalysts in terms of yield, diastereoselectivity, and enantioselectivity.     

Organocatalytic direct aldol and nitroaldol reactions between azetidine-2,3-diones and ketones or nitromethane

The reactions of enantiopure azetidine-2,3-diones with unmodified ketones or nitromethane were catalyzed by proline and N-methylephedrine, respectively, to give the corresponding 3-functionalized 3-hydroxy-β-lactams with good yields and total diastereoselectivities. It was observed that the use of both enantiomers of proline or of N-methylephedrine does result in identical levels of stereocontrol in the aldol and nitroaldol reactions.