Robert W. Armstrong

Use of a convertible isocyanide for generation of Ugi reaction derivatives on solid support: Synthesis of α-acylaminoesters and pyrroles

Abstract The Ugi four component condensation employing 1-isocyanocyclohexene as a convertible isocyanide has been adapted to solid supported synthesis. Using Wang or Rink resin and a linker derived from succinic anhydride, Ugi reactions proceeded smoothly. The products were then converted under acidic alcohol conditions to esters, acids, and to pyrroles via 1,3-dipolar cycloadditions to an acetylene. The intermediate in both transformations is a 1,3-oxazolinium-5-one arising from cycloelimination of the cyclohexenamide from the Ugi product.

Synthesis of ketones and aldehydes via reactions of Weinreb-type amides on solid support

Abstract Ketones and aldehydes were formed in low to good yields in reactions of Weinreb-type amides on solid support and no overaddition occurred.

Synthesis of trans-4-alkenyl oxazoles

Abstract Oxazoles with trans-4-alkenyl substituents were synthesized using a Wittig condensation of the corresponding tri-n-butylphosphonium ylids with aldehydes. The resulting 4-alkenyloxazoles were obtained with greater than 95% trans selectivity.

Highly convergent approach to the synthesis of the epoxy-amide fragment of the azinomycins

Abstract An efficient synthesis of the α-acyl amide fragment of the azinomycin antibiotics has been accomplished using the P asserini three-component condensation. Good diastereoselectivity was observed for a variety of isocyanide precursors.

Stereoselective synthesis of a tricyclic guanidinium model of cylindrospermopsin

Abstract An 11-step enantioselective synthesis of the A-ring of cylindrospermopsin is described using an intramolecular conjugate addition as the key step to forming the piperidine ring. Further elaboration generates a tricyclic guanidine via a sequential double displacement strategy as a model for the cylindrospermopsin guanidinium core.

Stereoselective methylations of bicyclic lactams derived from pyroglutamic acid

Abstract Reaction of the lithium enolate of (−) 7 with iodomethane provides a stereoselective synthesis of (2R,4S)-4-amino-2-methylpentanamide derivatives.

SMI2-MEDIATED SEQUENTIAL RADICAL CYCLIZATION/ANIONIC CAPTURE OF ARYL IODIDES ON SOLID SUPPORT

Abstract Aryl radicals were generated by SmI 2 on solid support, cyclized on to CC bond, and reduced to their organosamarium anionic species followed by electrophilic capture. However, the capture reaction was substrate-dependant in solution and on solid support. In some examples, results from solid phase reactions were equal or better to the corresponding solution reactions.

Stereoselective synthesis of “linear” C-disaccharides

Abstract A 1,4′-C-disaccharide ( 20 ) containing an acetylenic linkage was synthesized from D-glucose via a homologation of a 4-ulose derivative ( 6a ) followed by condensation with 2,3,4,6-tetrabenzyl pyranolactone. Subsequent reduction afforded isomerically pure β-C disaccharide in good overall yield.

Synthesis of 5-substituted nucleosides via the regioselective lithiation of 2′-deoxyuridine

Abstract Treatment of 2′-deoxy-3′,5′-bis-O-[(1,1-dimethylethyl)dimethylsilyl]-uridine with sec-BuLi in the presence of TMEDA resulted in a highly regioselective lithiation at C-5. The lithiated derivative was treated with a number of electrophiles to afford 5-substituted 2′-deoxyuridines.

Construction of Combinatorial Chemical Libraries Using a Rapid and Efficient Solid Phase Synthesis Based on a Multicomponent Condensation Reaction

Abstract A 96 member library of acylated dipeptides based on a known anticonvulsant was synthesized utilizing an Ugi four component condensation followed by derivitization through nucleophilic displacement of a Weinreb type amide. The library afforded compounds in reasonable yield and high purity after cleavage from solid support.