Peter L. Spargo

Highly diastereoselective 1,3-dipolar cycloaddition reactions of trans-2-methylene-1,3-dithiolane 1,3-dioxide with 3-oxidopyridinium and 3-oxidopyrylium betaines: a route to the tropane skeleton

The C2-symmetric vinyl sulfoxide, trans-2-methylene-1,3-dithiolane 1,3-dioxide, was found to react with a range of 3-oxidopyridinium betaines (bearing different substituents on nitrogen) in high yield and with total diastereoselectivity. A 2.3:1 mixture of regioisomers was formed with all of the 3-oxidopyridinium betaines but the ratio was found to change over prolonged periods of time due to reversibility of the minor regioisomer. 3-Oxidopyridinium betaines bearing methyl substituents at either the 2- or 6-position were also tested in the cycloaddition process. Improved regioselectivity (8:1) and again high diastereoselectivity were observed with the betaine having an additional substituent at the 2-position, but with betaines having a substituent in the 6-position although high regioselectivity was observed (9.9:1), the major isomer was formed with low diastereoselectivity (5.5:4.4). The origin of the regio- and diastereo-selectivity with all the betaines is discussed. Finally, the C2-symmetric vinyl sulfoxide, trans-2-methylene-1,3-dithiolane 1,3-dioxide was reacted with an oxidopyrylium betaine in moderate yield. Good regioselectivity and moderate diastereoselectivity were observed.

Production of cyclohexanone monooxygenase from Acinetobacter calcoaceticus for large scale Baeyer-Villiger monooxygenase reactions

Cyclohexanone monooxygenase was produced from Acinetobacter calcoaceticus grown on a medium containing both glutamate (30 g l−1) and cyclohexanol (1 g l−1). Productivity was increased to 650 U l−1, an order of magnitude greater than previous production methods, thereby enhancing the potential commercial utility of this enzyme.

(1R,3R)-2-Methylene-1,3-dithiolane 1,3-dioxide: a highly reactive and highly selective chiral ketene equivalent in cycloaddition reactions with a broad range of dienes

The chiral ketene equivalent trans-2-methylene-1,3-dithiolane 1,3-dioxide has been prepared in racemic and enantiomerically pure form in four steps. The key step in the asymmetric synthesis utilised a Modena asymmetric oxidation of 2-benzyloxymethyl-1,3-dithiolane which gave the trans bis-sulfoxide with high diastereocontrol (91∶9 in favour of trans) and high enantiocontrol (>97% ee). The ketene equivalent shows high selectivity (>97∶3) in Diels–Alder reactions with a range of simple dienes (cyclopentadiene, furan, 1-methoxybutadiene, Danishefsky’s diene, 1-methoxycyclohexa-1,3-diene) and shows high reactivity as it is able to undergo cycloadditions with notoriously unreactive dienes (cyclohexa-1,3-diene, 90∶10 selectivity; 2H-pyran-2-one, 94∶6 selectivity). Dihydropyridines also participated in cycloaddition reaction but with only moderate selectivity (73∶27). The Diels–Alder adducts can be readily deprotected to return the carbonyl group using a two step sequence involving reduction followed by hydrolysis.

Asymmetric Synthesis and Cycloaddition Chemistry of Trans-2-Methylene-1,3-Dithiolane 1,3-Dioxide

Abstract A study on the Modena oxidation of some 2-substituted 1,3-dithiolanes has led to an asymmetric synthesis of the chiral ketene equivalent trans-2-methylene-1,3-dithiolane 1,3-dioxide. Its reaction as a dipolarophile with aromatic betaines is also discussed.