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Andrew Cowley

Publications and source records attributed to Andrew Cowley.

11 recordsLinked to original sources
PubMed2006

New osmium-based reagent for the dihydroxylation of alkenes.

The cis dihydroxylation of alkenes is most efficiently accomplished by reaction with osmium tetroxide. Recently, the expense and toxicity of osmium tetroxide have led to a number of attempts to harness alternative osmium-based reagents, including microencapsulation and solid support techniques. We describe here the development of a new nonvolatile, stable, and recoverable osmium-based reagent devised for the stoichiometric cis dihydroxylation of alkenes. Although attempts to make this new dihydroxylation work with catalytic amounts of this reagent were unsuccessful, we did develop a sensitive test for free osmium tetroxide leached from the reagent in situ: this test may well have uses in probing future applications of derivatized osmium reagents.

Alkenes↗
PubMed2005

Utility of the ammonia-free Birch reduction of electron-deficient pyrroles: total synthesis of the 20s proteasome inhibitor, clasto-lactacystin beta-lactone.

A new synthesis of the 20S proteasome inhibitor clasto-lactacystin beta-lactone is described. Our route to this important natural product involves the partial reduction of an electron deficient pyrrole as a key step. By judicious choice of enolate counterion, we were able to exert complete control over the stereoselectivity of the reduction/aldol reaction. Early attempts to complete the synthesis by using a C-4 methyl substituted pyrrole are described in full, together with our attempts to promote regioselective elimination of a tertiary alcohol. The lessons learnt from this first approach led us to develop another, and ultimately successful, route that introduced the C-4 methyl group at a late stage in the synthesis. Our successful route is then described and this contains several highly stereoselective steps including a cis-dihydroxylation and an enolate methylation. The final synthesis proceeds in just 13 steps and in 15 % overall yield making it an extremely efficient route to this valuable compound.

Ammonia↗
PubMed2003

Potassium selective calix[4]semitubes.

A new class of ionophore consisting of two calix[4]arene units linked through the lower rim by two ethylene chains, in combination with propyl ether and phenolic functional groups, has been developed. These calix[4]semitube molecules exhibit remarkable selectivity and fast complexation kinetics for potassium over all Group 1 metal cations. Molecular modelling studies, using structural models derived from crystallographic data, suggest the potassium cation is complexed by a horizontal, side-on route and not through the calix[4]arene annulus. The length of the bridging alkylene chain between the respective calix[4]arenes of the semitube structure dictates the strength and selectivity of alkali metal cation binding.

Calixarenes↗
PubMed2003

Flexibility in the partial reduction of 2,5-disubstituted pyrroles: application to the synthesis of DMDP.

[reaction: see text] The partial reduction of electron-deficient 2,5-disubstituted pyrroles has been developed into a flexible procedure that gives control of relative stereochemistry by variation of the reduction conditions. After the reaction, the pyrroline products were dihydroxylated at C-3,4 to give either the cis or trans isomers; this flexibility means that a variety of polyhydroxylated pyrrolidines can be prepared in a short sequence. Finally, this method was applied to a synthesis of the naturally occurring glycosidase inhibitor DMDP.

Alkaloids↗
PubMed2002

The tethered aminohydroxylation (TA) of cyclic allylic carbamates.

The tethered aminohydroxylation of cyclic allylic carbamates is described using catalytic amounts of potassium osmate. The mechanism of reaction involves formation of an imido-osmium complex which adds intramolecularly to alkenes with complete control of both regio- and stereoselectivity: the formation of syn-aminodiol motifs is now straightforward using this chemistry. Proof of the mechanism was obtained with an X-ray crystal structure of an azaglycolate osmate ester intermediate.

Journal Article↗
PubMed2002

Synthesis of enantiopure dihydropyranones: aldol-based ring expansion of dihydrofurans.

[reaction: see text] The stereoselective Birch reduction of 3-methyl-2-furoic acids using a readily available chiral auxilairy is described; by coupling this process to an oxidative cleavage/aldol ring closure sequence we were able to produce highly functionalized and enantiopure dihydropyranones in high yield. This sequence has ample flexibility built into it, either by the use of different electrophiles during reductive alkylation or by subsequent derivatization of the dihydropyranone after ring expansion.

Alkylation↗