The stabilisation of I1 (Scheme 4) by electron delocalisation into the ester group prompted us to probe the regioselectivity of these reactions; namely, whether the use of an asymmetric alkyne would yield one, or several, regioisomers. Azophosphine 3 (MesN2P t Bu2), was thus reacted with an excess (20 equiv.) of ethyl 2-butynoate (H3CC≡C(CO2Et)) in toluene. After 4 days, only one major product was observed by P{ 1 H} NMR spectroscopy, which after work-up was observed to be product 9 (Figure ). This regioisomer could be confirmed in solution by 2D-NOESY NMR spectroscopy, as a nOe (nuclear Overhauser effect) could be observed between the t Bu groups and the methyl protons bound to the ring (-C=CCH3), but not between the t Bu groups and any of the protons on the ester groups. Single crystals of 9 were grown via slow evaporation of a concentrated hexane solution, and SXRD confirmed the product as the expected regioisomer (Figure ). The bond metric data for 9 are very similar to those previously discussed for 4 and 6. Scheme 6. Regioselective synthesis of heterocycles 9 (A) and 10 (B) via the reaction of azophosphines with ethyl 2-butynoate. (17). 9 crystallised with two product molecules in the asymmetric unit; only one is shown here for clarity. Thermal ellipsoids were drawn at the 50% probability level. The analogous reaction with azophosphine 1 (MesN2P i Pr2) was attempted, as the smaller Psubstituents could potentially enable access ot the corresponding seven-membered ring. Azophosphine 1 was reacted with an excess (12 equiv.) of ethyl 2butynoate overnight in toluene (Scheme 6B). Complete consumption of the azophosphine was observed by 31 P{ 1 H} NMR spectroscopy, and formation of a new species at 72.4 ppm, consistent with formation of a five-membered heterocycle, although we were unable to cleanly isolate this species. There was no evidence of any formation of the seven-membered ring, despite the excess of the alkyne used, which we postulate is due to the reduced electrophilicity of ethyl 2-butynoate compared to diethyl acetylenecarboxylate (i.e. the analogous barrier that would correpsond to TS3 from Scheme 5 in this system is too high to be accessible). However, subsequent addition of an excess (6 equiv.) of the more reactive diethyl acetylenedicarboxylate ((C(CO2Et))2) to this compound yielded species 10 as the sole product. Single crystals of 10 were grown via slow evaporation of a hexane solution, for which SXRD confirmed the product as the expected regioisomer of the seven-membered ring (Figure ); this structural assignment was again supported by 2D-NOESY NMR spectroscopy. The formation of products 9 and 10 demonstrate the regioselective synthesis of five-and seven-membered rings from azophosphines.