Fluorous mixture synthesis of 4-alkylidene cyclopentenones via a rhodium-catalyzed [2+2+1] cycloaddition of alkynyl allenes.
Fluorous mixture synthesis was used to prepare a library of 4-alkylidene cyclopentenones starting from a mixture of four alpha-amino acid derivatives tagged with different fluorous benzyl carbamates ((F)CBz) of varying fluorine content. The amino acids were converted to the corresponding propargyl esters and then subjected to an ester-enolate Claisen rearrangement to give a mixture of allenic amino esters. The allenes were then split four ways and propargylated with different propargyl bromides to give four mixtures of alkynyl allenes. The 4-alkylidene cyclopentenones were formed by a formal [2+2+1] cycloaddition of the alkynyl allenes using catalytic [Rh(CO)2Cl]2 under CO atmosphere. Demixing by fluorous preparative HPLC, removal of the fluorous benzyl carbamates, and then exposure to HCl/ether gave the hydrochloride salts of 16 compounds as diastereomeric mixtures in 69-99% purity. Thus, after just 26 chemical steps, a library of 16 cyclopentenones was prepared by using fluorous mixture synthesis. By comparison, the same library would have required 112 steps if each compound were made individually by parallel synthesis.
Manku
Sukhdev
S
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Curran
Dennis P
DP
D000466:Alkadienes / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*
D000466:Alkadienes; D000470:Alkaloids; D003517:Cyclopentanes; D005461:Fluorine; C025947:propadiene; D012238:Rhodium; C003380:tecomine; C013905:cyclopentenone