The stereocontrolled formation of cis-2,5-disubstituted tetrahydrofurans and cis-2,6-disubstituted tetrahydropyrans is achieved from enantiopure ketosulfinyl esters by reduction, Weinreb's amide, and ketone formation, followed by the reductive cyclization (Et3SiH/TMSOTf) of the resulting hydroxysulfinyl ketones. The sulfoxide-bearing heterocycles were transformed into two natural products, (−)-centrolobine (1) and both enantiomers of cis-(6-methyltetrahydropyran-2-yl)acetic acid (2).

Reductive cyclizations of hydroxysulfinyl ketones: enantioselective access to tetrahydropyran and tetrahydrofuran derivatives.

Fungal phenalenones: chemistry, biology, biosynthesis and phylogeny.

Synthesis of C1-alkyl- and acylglycals from glycals using a B-alkyl Suzuki-Miyaura cross coupling approach

A range of enol ethers, linked via their oxygen atom to the anomeric centre of a pyran ring system, was shown to undergo oxygen to carbon rearrangement upon treatment with a Lewis acid to give the corresponding 2-carbon substituted products. At low temperature, trimethylsilyl trifluoromethanesulfonate catalysed rearrangements of anomerically linked 6-substituted tetrahydropyranyl enol ethers gave selectively the trans-pyranyl ketones, whereas at higher temperatures selective formation of the cis-pyranyl ketones was observed. In a simple application of the methodology the cis-selective rearrangement was used as the key step in a concise total synthesis of a constituent of civet.

Diastereoselective oxygen to carbon rearrangements of anomerically linked enol ethers and the total synthesis of (+)-(S,S)-(cis-6-methyltetrahydropyran-2-yl)acetic acid, a component of civet

In the presence of HSO3F/Ac2O in CH2CL2, 2-exo- and 2-endo-cyano-5,6-exo-epoxy-7-oxabicyclo[2.2.1]hept-2-yl acetates (6a, b) gave products derived from the epoxide-ring opening and a 1,2-shift of the unsubstituted alkyl group (σ bond C(3)–C(4)). In contrast, under similar conditions, the 5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one (6c) gave 5-oxo-2-oxabicyclo[2.2.1]heptane-3,7-diyl diacetates 20 and 21 arising from the 1,2-shift of the acyl group. Acid treatment of 5,6-exo-epoxy-2,2-dimethoxy-7-oxabicyclo[2.2.1]heptane (6d) and of 5,6-exo-epoxy-2,2-bis(benzyloxy)-7-oxabicyclo[2.2.1]heptane (6e) gave minor products arising from epoxide-ring opening and the 1,2-shift of σ bond C(3)–C(4) and major products (25, 29) arising from the 1,3-shift of a methoxy and benzyloxy group, respectively. Under similar conditions, 5,6-exo-epoxy-2,2-ethylenedioxy-7-oxabicyclo[2.2.1]heptane (6f) gave 1,1-(ethylenedioxy)-2-(2-furyl)ethyl acetate (32, major) and a minor product 33, arising from the 1,2-shift of σ bond C(3)–C(4). The following order of migratory aptitudes for 1,2-shifts toward electron-deficient centers has been established: acyl > alkyl > alkyl α-substituted with inductive electron-withdrawing groups. This order is valid for competitive Wagner-Meerwein rearrangements involving equilibria between carbocation intermediates with similar exothermicities.

Acid-catalyzed rearrangements of 5-6-exo-epoxy-7-oxabicyclo[2.2.1]hept-2-yl derivatives. Migratory aptitudes of acyl vs. alkyl groups in Wagner-Meerwein transpositions

The title compound (1) has been synthesized in seven steps and in 42% overall yield from the nucleophilic diene (2). The relative configuration of (1) has been confirmed by a single-crystal X-ray study.

Stereoselective Synthesis of (±)-(cis-6-Methyltetrahydropyran-2-yl)acetic Acid

Low-temperature determinations of the crystal structures of the naturally occurring quinones ventilagone (as its p-bromobenzyl ether) and dunnione (as its p-bromophenylhydrazone) permit the assignment of their absolute configurations as (1R,3S)-7,10-dihydroxy-1,3,8-trimethyl-3,4,6,9-tetrahydro-1H-naphtho[2,3-c]-pyrane-6,9-dione 1 and (2R)-2,3-dihydro-2,3,3-trimethylnaphtho[1,2-b]furan-4,5-dione 2.

Absolute configurations of naturally occurring quinones: Ventilagone and dunnione

The utility of preparing cis-2,6-disubstituted 5,6-dihydro-2H-pyrans by the methodology implied in Scheme 1 is demonstrated through the preparation of the two pyrans (1) and (2). The overall yields for the two nine-step sequences starting from the enals (3) and (4) were 57 and 54%, respectively, whilst the overall diastereochemical yield approached 100%. The key features of the method are (i) a highly regioselective Lewis acid-catalysed cyclocondensation reaction of a nucleophilic diene with an aldehyde to afford a 2,3-dihydro-4H-pyran-4-one, (ii) reduction of a pyranone with better than 98% regio- and stereo-chemical control to give the corresponding glycal, and (iii) an ester enolate Claisen rearrangement of a glycal acetate.

A General and Diastereoselective Approach to the Preparation of cis-2,6-Disubstituted Pyrans

The crystal structure of the title compound has been determined by single-crystal X-ray diffraction at 295 K and refined by least squares to a residual of 0.064 for 775 ?observed? reflections. The structure determination confirms the stereochemistry previously proposed for the molecule. Crystals are monoclinic, P21/n, a 11.131(7), b 18.908(3), c 7.121(5) Ǻ, β 104.56(5)°, Z 4.

B. L. Johnson

Papers

Stereoselective Synthesis of (±)-(cis-6-Methyltetrahydropyran-2-yl)acetic Acid

Absolute configurations of naturally occurring quinones: Ventilagone and dunnione

A General and Diastereoselective Approach to the Preparation of cis-2,6-Disubstituted Pyrans

Crystal structure of exo-6-Bromo-exo-tricyclo[3,2,1,02,4]oct-anti-8-yl p-Nitrobenzoate

Stereoselective Synthesis of (.+-.)-(cis-6-Methyltetrahydropyran-2-yl) acetic Acid.