New innovations in rhodium catalyzed transformation of alpha-functionalized alkynes utilizing carbon monoxide and hydrogen.

Abstract

Identifying the important roles that functional groups play when substituted alkynes are placed under hydroformylation conditions (reactions incorporating carbon monoxide and hydrogen gas with catalytic amounts of a rhodium complex) is a valuable tool for organic synthesis. Novel and unexpected chemistry have resulted from establishing the primary and secondary roles of certain functional groups. The primary role is the ability to direct a rhodium complex to add to a triple bond, and the secondary role involves directing the type of chemistry that will take place after the addition. The following examples demonstrate this dual relationship resulting in the preparation of alpha,beta-unsaturated aldehydes, N-heterocyclec enols, and important ring systems with potential biological activity. The selected 5-membered heterocycles generated are important materials in treating inflammatory diseases, cancer and heart disease, as well as allowing for the inhibition of HIV protease. The reaction of aliphatic 1-en-3-ynes with synthesis gas in the presence of the zwitterionic rhodium complex, (eta6-C6H 5BPh3)-Rh+(1,5-COD) and triphenyl phosphite afford formyl-dienes in high regioselectivity, and in 50 to 70% isolated yields. As well, the hydroformylation of 2-acetylenic thiophenes afford, as the major product, the alpha,beta-unsaturated aldehyde with the aldehyde and thiophene attached to the same olefin carbon atom. Excellent regioselectivities of 64 to 100% and additive yields of 65 to 97% were obtained when the acetylenic unit is a propargyl ether or ester, phenylacetylene, or an enyne. alpha-Keto alkynes react with CO/H2 in the presence of catalytic quantities of the zwitterionic rhodium complex and triphenyl phosphite to form either the 2-, 2(3H)- or 2(5H)-furanones in 61--93% yields. In addition, the tandem cyclohydrocarbonylative/CO insertion of alpha-imino alkynes afford aldehyde substituted pyrrolinones in 67 to 82% yields. Hydrocarbonylative enolation of 2-acetylenic thiazoles in the presence of CO, H2 and catalytic quantities of the zwitterionic rhodium complex and triphenyl phosphite afford (Z)-2-thiazol-2-ylalk-1en-1ols in 61 to 90% yields. The extension of the hydrocarbonylative enolation to 2-acetylenic benzoxazoles give (Z)-2-benzoxazol-2-ylalk-1-en-1-ols in 37 to 87% yields.