Pii: S0040-4039(97)01761-9

The regioselectivity of 1,3-dipolar cycloaddition reactions between mesoionic compounds with singly-tethered substituents is examined. The results with propitiate dipolarophiles are compared with other singly and doubly-tethered examples according to a model using an asynchronous, concerted transition state. The isolation and reaction of a novel, nonaryl substituted mesoionic compound 7 is reported. A regiodirected synthesis starting with N-(2-thiazolinyl)proline gives a complementary, dihydropyrroline compared with the reaction between N-formylproline and alkyl propitiates. © 1997 Elsevier Science Ltd, We have been examining factors influencing the regiochemical outcome of 1,3-dipolar cycloaddition reactions of mtinchnones and related mesoionic compounds with acetylenic dipolarophiles. Previously, we elaborated the conventional Frontier Molecular Orbital (FMO) model to include the synchronicity of the bond formations during the cycloaddition based on differential torsional accessibility of the reacting centers as well as non-covalent interactions between the groups on those centers. 1,2 For example, we interpreted the remarkable difference in regioselectivity between our mtinchnones l a -b 2,3 (Eq. 1) and Pizzorno's 2a-b 4,5 (Eq. 2) as the ability for the untethered C-2 centers in 2a-b to become more pyramidalized at the transition state, thereby allowing for a greater degree of bond formation with the B-carbon of the propitiate dipolarophile. Our view of this transition state structure, which is also supported by previous computational searches, is represented by I in Equation 2. H E E H E R2 R1 R2 R1 R2 R1 3 I 0 I I CH 3 CH 3 CH3 la : R1 = CH3, R2 = 13CH3 55 : 45 lb : R1 = 13CH3, R2 = CH3 55 : 45 E = CO2CH3 ,o E[° ]co2 H ~ nTnnTnnTnnTnnTn ~ 2a : n = 1 I I n completely 2b : n = 2 I regioselective *internet: [email protected]; fax (USA): 313-647-4865 tpresent address: Pfizer, Inc., Central Research Division, Eastern Point Road, Groton, CT 06340