Individual enantiomers of substituted cyclohexyl diazoacetates or 2-octyl diazoacetates matched with a configurationally suitable chiral dirhodium(II) carboxamidate catalyst provide an effective methodology for the synthesis of lactones with exceptional diastereo- and regiocontrol. Enantiomerically pure (1S,2R)-cis-2-methylcyclohexyl diazoacetate forms the all-cis-(1R,SR,9R)-9-methyl-2-oxabicyclo[4.3.0.]nonan-3-one with complete diastereocontrol in re actions catalyzed by dirhodium(II) tetrakis [methyl 1-(3-phenylpropanoyl)-2-oxoimidazolidine-4(R)-carboxylate], Rh-2(4(S)-MPPIM)(4), but the configurational mismatch results in a mixture of products. The same diazoacetate produces (1S,SR)-5-methyl-2-oxabicyclo[4.3.0]nona-3-one with virtually complete selectivity by catalysis with dirhodium(II) tetrakis[methyl 2-oxopynolidine-5(S)-carboxylate], Rh-2(5(S)-MEPY)(4). Similarly high stereo- and regiocontrol is also achieved with enantiomerically pure trans-2-methylcyclohexyl diazoacetates. Product control from insertion reactions of d- or l-menthyl diazoacetate and (+)-neomenthyl diazoacetate from the configurational match with dirhodium(II) catalyst results in the formation of one C-H insertion product in high yield. The exceedingly high product diastereoselection observed in these reactions is consistent with virtually exclusive insertion into equatorial C-H bonds. The catalyst-dependent selective formation of a cis-disubstituted gamma-butyrolactone or a beta-lactone from 2-octyl diazoacetate has been achieved. Control of product diastereoselectivity and regioselectivity in C-H insertion reactions is explained by conformational suitability in configurational match/mismatch of catalyst and carbene.