Letters in Organic Chemistry - Volume 1, Issue 4, 2004

Organocatalysis is one of the most vibrant research areas in synthetic chemistry at present. In this short review, some of the impressive recent advances in organocatalysis are discussed. Papers published in 2004 describing the use of (i) enamine type activation of aldehydes and ketones, and (ii) catalysis that proceeds by the formation of hydrogen bonds are highlighted.

The title macrosphelides were synthesized by using two-step conversion of furans into γ-oxo-α,β- unsaturated carboxylic acids as a key step. In the case of macrosphelide H, AcCH2 group at C(3) was constructed from CH2=CHCH2 by Wacker oxidation under modified conditions.

An improved synthesis of the C23-C35 moiety of reidispongiolide A has been completed. An intermolecular Nozaki-Hiyama-Kishi coupling was employed for the union of C23-C30 and C31-C35 fragments. A discussion on the factors influencing the stereochemical outcome of (E)-crotylboration reactions of α-methyl-βl-alkoxy aldehydes is also presented.

The photocyclisation of enantiomerically pure α-heteroatom-substituted β-methyl butyrophenones 1 results in Norrish II cleavage and in Norrish II / Yang cyclisation products, cyclobutanols 2, the latter being formed with excellent diastereoselectivities and with relative yields which were strongly depending on the Hbonding activity of the α-substituent.

The efficient synthesis of the common C1-C32 precursor of trans and cis solamins has been achieved with the longest linear sequence of 7 steps from pentadecalactone. The key transformations rely on the iron (III) catalysed Grignard coupling reaction with a vinyl bromide, and the Sharpless asymmetric dihydroxylation. Mitochondrial complex I activity of these annonaceous synthetic precursors highlighted the crucial influenc Read More

A direct route to erythrinanes has been completed by a sequence that involves diastereoselective conjugate addition on a α,β-unsaturated lactam, followed by a ring-closing metathesis reaction to construct ring A. The synthesis of the key intermediates C-10b functionalized dihydropyrroloisoquinolines is achieved via Parham cyclisation and α-amidoalkylation reactions.

Rapid syntheses of nitroheterocycles that bear a diethyl methylenemalonate group ?β to a nitro group starting from easily available nitroheterocyclic sulfones and involving, a one-pot substitution-elimination with either diethyl bromomalonate or an original direct olefination with diethyl ketomalonate, gave moderate yields in nitroimidazole series. An SRN1 reaction followed by a base-mediated nitrous acid eliminat Read More

Enantioenriched α-hydroxy acids and esters have been synthesized by oxidation of (S,S)-(+)- pseudoephedrine arylacetamide enolates with different reagents. We have found that the oxidation of these enolates proceeds with good yields and diastereoselectivities and, interestingly, we have also noticed that the use of different oxidation reagents allows the selective preparation of any of the two possible epimers of the t Read More

Nitroalkanes react with chiral acrylates in the presence of a catalytic amount (10% mol) of CTAOH in small amount of water as solvent. Although only modest levels of diastereoselectivity can be observed in this process, the obtained Michael adducts can be easily transformed into interesting building blocks as γ-amino acids and cyclic hydroxycarbamates.

Thermolysis of C,C-disubstituted N-(2-benzylideneamino)benzyl ketenimines in solution provided 2,2-disubstituted 3-(2-benzylideneamino)phenylpropionitriles by [1,3] migration of the substituted benzyl group from nitrogen to carbon in the ketenimine fragment.

A novel one-pot method to 1-[(1-phenyl-1-dialkoxyphosphoryl)-methyl]-2-pyrrolidinones (1a-c), where R=Me, Et, n-Hex, from the benzaldehyde (2), 4-aminobutyric acid (3) and dialkyl phosphite (4a-c) has been developed with reasonable 61-80% yields. Preparation of 4-{[(dimethoxyphosphoryl)-phenyl-methyl]- amino}-butyric acid (5) with high 85% yield is also described. Unexpected large 5JHP coupling constants 3.35, 3.37 and Read More

Titanium tetraiodide promoted reductive coupling reaction of aldehydes with nitriles gave α- hydroxy imines in good yields.

3,4,6-Trisubstituted-2-pyrone synthesis via the nucleophilic addition of 2-alkyl Meldrum's acid to alkynyl ketone has been developed. The reaction of 2-alkyl Meldrum's acid with alkynyl ketones provided 3,4,6-trisubstituted-2-pyrones in good yields. The reaction of dialkynyl ketones gave 6-alkynyl-2-pyrones.

The regioselectivity of the double nucleophilic addition of ketene silyl acetals to α,β-unsaturated imines was highly depended on the subtle difference of the reactivity of the ketene silyl acetals, and the factors were mainly derived from the ability of the ketene silyl acetals to undergo the silicon-aluminum exchange reaction, where the aluminum enolate preferentially underwent 1,4-addition.

(E)-β-Substituted styrenes were obtained stereoselectively by the titanocene(II)-promoted desulfurizative coupling of thioacetals with styrenes. It is suggested that the reaction proceeds through the regioselective formation of a titanacyclobutane intermediate, followed by ?-elimination.

β-Chloro-α,β-unsaturated ketones or β-ethoxy-α,β-unsaturated ketones, depending on the solvent used, are conveniently prepared in one step and in good yields by treating cycloenones 1 - 10 with niobium pentachloride.

The carbolithiation of 1-lithiohex-5-ene (2) gives cyclopentylmethyllithium (3), which after treatment with zinc dibromide yields a solution of the corresponding organozinc reagent (5). The palladium(II)-catalysed acylation of this compound with several acyl chlorides yields the expected ketones (6). By a copper(I)-promoted reaction of compound (5) with different allylic or propargylic chlorides or bromides, a very clean S Read More

Substituted thiophenes can act as dienophiles in normal electron demand Diels-Alder reactions, nitro being one of the substituents. Cycloaddition with Danishefsky's diene provides the benzothiophene derivatives with nitro side selectivity, α-substituted substrates being the more dienophilic. The reaction with isoprene leads mainly to the corresponding (pyrrol-1-yl)thiophenes.

The 4-nitrophenylsulfonyl, the benzothiazolsulfonyl and the anthracenesulfonyl protecting groups were evaluated in the protection of the phenylisoserine side chain, as part of a semisynthesis of paclitaxel. The mechanism for the cleavage of the anthracenesulfonyl group using thiols was also examined, and found to proceed by an addition elimination pathway, which is in contrast to the reported reductive mechanism. Read More