Enantioselective Intramolecular Cyclopropanations of Allylic and Homoallylic Diazoacetates and Diazoacetamides Using Chiral Dirhodium(II) Carboxamide Catalysts

Abstract

Diazo decomposition of allylic and homoallylic diazoacetates loa-p and 22a-j catalyzed by chiral dirhodium(I1) tetrakis[methyl 2-pyrrolidone-S(S)-carboxylate], Rhz(SS-MEPY)4 (7), and its enantiomer, Rhz(5RMEPY)4 (S), produces the corresponding intramolecular cyclopropanation products l la-p and 23a-j in good to excellent yields and with exceptional enantioselectivity. Higher enantiocontrol is observed with allylic diazoacetates than with their homoallylic counterparts, but allylic diazoacetates are subject to greater variations in enantioselectivities with changes in substitution patterns on the carbon-carbon double bond. For example, the enantioselectivities in the intramolecular cyclopropanations of 3-allcyl/aryl-2(Z)-alken-l-y1 diazoacetates are generally 194%, whereas the cyclizations of the homologous 4-alkyl/aryl-3(Z)-alken1-yl diazoacetates are typically in the range of 70-90% ee. The corresponding 3-alkyYaryl-2(E)-alken-l-y1 and 4-alkyl/aryl-3(E)-alken-l-yl diazoacetates undergo cyclization with slightly lower ee’s (54-85%). Although the Rh@-MEPY)4-catalyzed cyclization of the 2-methallyl diazoacetate 1Oc proceeds with only 7% ee, alternative chiral dirhodium(I1) catalysts, including those with methyl N-acylimidazolidin-2-one-4(S)-carboxylate ligands such as Rh2(4S-MACIM)4 (14) and Rhz(4S-MPAIM)d (E) , may be employed to increase the level of enantiocontrol to 78 and 65%, respectively. Some allylic diazoacetamides also undergo highly enantioselective cyclization to form cyclopropyl lactams as illustrated by the diazo decomposition of N-allyl diazoacetamide (19) in the presence of dirhodium(II) tetrakis[methyl 2-oxazolidinone-4(S)-carboxylate], Rhz(4SMEOXk, to give the 3-azabicyclo[3.1.0]hexan-2-one 20 in 98% ee. The absolute configuration and the level of enantiocontrol in these intramolecular cyclopropanations have been interpreted by a transition state model in which the important determinants are (i) the preferred conformation about the rhodium-carbon bond; (ii) the trajectory of approach of the double bond to the metallocarbene center; and (iii) the orientation of the double bond with respect to the chiral face of the catalyst.