ELECTRONIC AND STERIC CONTROL IN CARBON HYDROGEN INSERTION REACTIONS OF DIAZOACETOACETATES CATALYZED BY DIRHODIUM(II) CARBOXYLATES AND CARBOXAMIDES

Carboxylate and carboxamide ligands on dirhodium(II) catalysts can provide enormous regiocontrol in carbon-hydrogen insertion reactions of diazoacetate esters. Whereas 2,3,4-trimethyl-3-pentyl diazoacetoacetate (1) forms gamma-lactone products from insertion into primary and tertiary C-H bonds in a statistical distribution (61:39) with dirhodium(II) tetrakis(perfluorobutyrate), only tertiary C-H insertion is observed with dirhodium(II) tetraacetamide. Similar results are obtained with 2-methyl-2-octyl diazoacetoacetate (3), where competition for insertion exists between secondary and primary C-H bonds and electronic factors govern regioselection. However, with 2-methyl-3-isopropyl-3-heptyl diazoacetoacetate (2) and 2-methyl-1-phenyl-2-propyl diazoacetoacetate (4), product distributions from C-H insertion are invariant with the dirhodium(II) ligands; insertion into a secondary C-H bond is favored over tertiary C-H insertion with 2 (95:5), and insertion into a primary C-H bond is preferred to benzylic secondary C-H insertion with 4 (70:30). In such cases, which are amenable to analyses by MM2 calculations, regioselectivity is determined by conformational preferences for which C-H insertion selectivity can be as random as that found with 2 and 4. When only one C-H bond site is available for insertion to form a five-membered ring product, only one gamma-lactone is observed from reactions catalyzed by dirhodium(II) tetraacetate, and that product is not necessarily the one predicted by presumed electronic preferences.