Catalytic enantioselective C-H activation by means of metal-carbenoid-induced C-H insertion.

Syntheses of gem-dihalocyclopropanes and their use in organic synthesis

Progress in the construction of cyclooctanoid systems: new approaches and applications to natural product syntheses.

The most recent papers describing the stereoselective synthesis of cyclic quaternary α-amino acids are collected in this review The diverse synthetic approaches are classified according to the size of the ring and taking into account the bond that is formed to complete the quaternary skeleton

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Recent progress on the stereoselective synthesis of cyclic quaternary α-amino acids

Radicals in organic synthesis: part 2

Pyruvate decarboxylase from Saccharomyces sp. catalysed the formation of acetoin of predominantly the opposite configuration than that obtained using the enzyme from Zymomonas mobilis. A similar result was obtained for the lactaldehyde formed in the pyruvate decarboxylase-catalysed decarboxylation of glyoxylate in the presence of acetaldehyde. The results are interpreted in terms of different Boltzmann distributions for the two enzymes between the enzyme–substrate complexes of acetaldehyde bound on its re and si faces respectively.

Stereochemistry of the formation of lactaldehyde and acetoin produced by the pyruvate decarboxylases of yeast (Saccharomyces sp.) and Zymomonas mobilis: different Boltzmann distributions between bound forms of the electrophile, acetaldehyde, in the two enzymatic reactions

Separate treatment of the iodotrienedione 19 and the iododienynedione 38 with Bu3SnH–AIBN produces the corresponding taxane ring systems 25 (25–30%) and 56 (50–60%) respectively by way of tandem radical macrocyclisation-radical transannular cyclisations. By contrast the analogous iodopolyenones 61, 63, 65a, 66a, 86a and 87a, together with the corresponding iodoenynones 39a and 59 failed to undergo similar tandem radical reactions, and instead gave products resulting from direct reduction of the carbon–iodine bonds in these substrates. The structures of the taxane analogues 25 and 56 followed from analysis of their NMR spectroscopic data and comparison with similar NMR data for related taxoids described in the literature. The stereochemistry of 56 was secured from an X-ray crystal structure determination of the 1,5-diol 57 produced from reduction of 56 with DIBAL.

A tandem radical macrocyclisation-transannular cyclisation approach towards the taxanes

We have developed a short enantioselective synthesis of (2R)-hydroxymethyl glutamic acid (HMG) starting from Garner's aldehyde using an alkylidene carbene 1,5-CH insertion as a method to construct the quaternary stereocenter. A variety of conditions were examined for the oxidative cleavage of the key cyclopentene intermediate and we found that RuCl3/NaIO4 led directly to the desired amino bis-acid product. We were also able to show that oxidative cleavage of the cyclopentene 1,5-CH insertion product could be used to produce the amino acid-containing skeleton of the sphingofungin family of natural products.

An efficient enantioselective synthesis of (2R)-hydroxymethyl glutamic acid and an approach to the (2R)-hydroxymethyl-substituted sphingofungins.

A cascade radical-mediated Diels–Alder reaction with the iododienynone 16b produced the tricyclic ketone17 (22%). By contrast, treatment of the substituted furans36 and 47 with Bu3SnH–AIBN, instead led to the tetracycles 44 and 58 respectively, rather than the anticipated oestranes, i.e.38 and 48. In a separate study, attempted cascade radical-mediated cyclisations from the ortho-aryl substituted iododienynones 72 and 73, leading to the ring-D aromatic steroid7, instead gave the macrocyclic ketone76 or the novel bridged tricycles 77/82, respectively, depending on whether benzene or heptane was used as solvent in the reactions.

Cascade radical-mediated cyclisations with conjugated ynone electrophores. An approach to the synthesis of steroids and other novel ring-fused polycyclic carbocycles.

An enantioselective synthesis of the α,α-dialkyl-α-amino acid (1S,3R)-ACPD has been achieved using an alkylidene carbene 1,5-CH insertion reaction as a key step. The ketone cyclization precursor was synthesized from Garner's aldehyde in high yield via a Wittig homologation and subsequent catalytic hydrogenation. Treatment of the ketone with 1.2 equiv of lithio(trimethylsilyl)diazomethane in THF resulted in the formation of the corresponding cyclopentene-containing CH-insertion product in 62−69% yield in high enantiomeric excess. Subsequent functional group manipulation allowed the synthesis of the amino acid (1S,3R)-ACPD to be completed.

Nicholas M. Thomson

Papers

Stereochemistry of the formation of lactaldehyde and acetoin produced by the pyruvate decarboxylases of yeast (Saccharomyces sp.) and Zymomonas mobilis: different Boltzmann distributions between bound forms of the electrophile, acetaldehyde, in the two enzymatic reactions

A tandem radical macrocyclisation-transannular cyclisation approach towards the taxanes

An efficient enantioselective synthesis of (2R)-hydroxymethyl glutamic acid and an approach to the (2R)-hydroxymethyl-substituted sphingofungins.

Cascade radical-mediated cyclisations with conjugated ynone electrophores. An approach to the synthesis of steroids and other novel ring-fused polycyclic carbocycles.

Enantioselective synthesis of the excitatory amino acid (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid.