J. Stephen Clark

Diastereoselective Anti Aldol Reactions of Chiral Ethyl Ketones. Enantioselective Processes for the Synthesis of Polypropionate Natural Products.

Abstract The diastereoselective anti aldol reactions of the β-keto imide 3a , the related ethyl ketone 20b , and its diastereomer 22b have been studied. In these aldol reactions, the chiral ethyl ketones 3a and 20b were found to exhibit the opposite sense of asymmetric induction in the analogous anti aldol bond constructions from the derived ( E ) boron enolates. The relevance of this study to the synthesis of polypropionate natural products is discussed.

Synthesis of brevetoxin sub-units by sequential ring-closing metathesis and hydroboration

Abstract A new strategy for the construction of polycyclic ethers by sequential ring-closing metathesis and stereoselective hydroboration has been explored. This sequence of reactions has been used to prepare bicyclic ethers corresponding to sub-units of brevetoxin B.

Enantioselective synthesis of medium-ring sub-units of brevetoxin A by ring-closing metathesis

Abstract A new strategy for the enantioselective synthesis of eight- and nine-membered cyclic ethers corresponding to sub-units of brevetoxin A has been developed. The strategy involves the use of ring-closing metathesis reactions of allylic ethers to effect ring construction.

Asymmetric Synthesis of Cyclic Ethers by Rearrangement of Oxonium Ylides Generated from Chiral Copper Carbenoids

Abstract Tetrahydrofuran-3-ones and tetrahydropyran-3-ones can be prepared enantioselectively by rearrangement of the ylide-type intermediates generated by the reaction of a chiral copper carbenoid with the oxygen atom of a pendant allylic ether. Cyclic ethers with enantiomeric excesses of up to 57% have been obtained using a copper complex of the enantiomerically pure diimine 1a for carbenoid generation.

Synthesis of cyclic ethers from copper carbenoids by formation and rearrangement of oxonium ylides

Abstract Copper carbenoids undergo efficient intramolecular insertion into allyl ethers, and the resulting ylide-type species rearrange to furnish cyclic ethers (ring sizes 6–8) in high yield. Copper(II) hexafluoroacetylacetonate is an extremely efficient catalyst for this reaction, and use of this complex minimises competing C-H insertion.

Diastereoselective synthesis of 2,5-dialkyl tetrahydrofuran-3-ones by a copper-catalysed tandem carbenoid insertion and ylide rearrangement reaction

Cu(acac)2-catalysed cyclisations of the α-diazo ketones 3, result in the diastereoselective formation ( > 97:3) of the trans-2,5-dialkyl tetrahydrofuran-3-ones 4. The yields and levels of diastereoselection are catalyst, solvent, and temperature dependent.

An enantioselective synthesis of the CE ring system of the alkaloids manzamine A, E and F, and ircinal a

Abstract An efficient enantioselective synthesis of the azabicyclo[6.3.0]-undecane 6, corresponding to the CE ring system found in the manzamines A, E, and F, and ircinal A, from (S)-prolinol is described. The key step in the route to 6 was the intramolecular generation and rearrangement of the spiro-fused bicyclic ylide 5 from a copper carbenoid.

Synthesis of sub-units of marine polycyclic ethers by ring-closing metathesis and hydroboration of enol ethers

Abstract The construction of polycyclic ethers by sequential ring-closing metathesis and stereoselective hydroboration of enol ethers has been explored. This reaction sequence has been used to prepare bicyclic ethers corresponding to sub-units found in the brevetoxins and related marine natural products.

A strategy for the asymmetric synthesis of medium ring oxygen heterocycles: Enantioselective total synthesis of (+)-octahydrodeacetyldebromolaurencin

Abstract The asymmetric synthesis of the laurencin degradation product ( 2 ) by methylenation of the chiral heptanolide ( 5 ), conformationally controlled hydroboration of the enol ether ( 6 ), to give exclusively the cis -alcohol ( 7 ), and introduction of the pentyl side chain, demonstrates a new approach to the enantioselective synthesis of 2,8-disubstituted oxocanes, and confirms the absolute configuration of laurencin ( 1 ).

A short synthesis of (±)-decarestrictine L

Abstract A stereoselective synthesis of (±)-decarestrictine L ( 1 ) from protected pentane-1,4-diol ( 2 ) is described. The key intermediate, tetrahydropyran-3-one 5a , was obtained by a tandem intramolecular carbenoid insertion and ylide rearrangement reaction.