Diastereo- and regioselectivity in Diels–Alder reaction of [1,4 diazaphospholo[4,5-a]pyridines Raj K. Bansal, a, * Konstantin Karaghiosoff, b Neelima Gupta, a Neelam Gandhi a and Surendra K. Kumawat a a Department of Chemistry, University of Rajasthan, Jaipur 302 004, India b Department Chemie und Biochemie, Ludwig-Maximilians-Universita ¨ t, Butenandtstr. 5-13, D-81377 Mu ¨ nchen, Germany Received 12 May 2005; revised 22 July 2005; accepted 11 August 2005 Available online 31 August 2005 Abstract—[1,4,2]Diazaphospholo[4,5-a]pyridines undergo diastereoselective Diels–Alder reaction at the OC]P– functionality dimethylbutadiene and isoprene in the presence of sulfur or selenium. The reaction with isoprene occurs regioselectively. reaction with diene in presence of methyl iodide, the initially formed [2C4] cycloadduct is methylated regioselectively at th 2 ,l 3 -nitrogen. The results of the DFT calculations of the Diels–Alder reaction with isoprene are in accord with the observed regioselectivit stabilities of the two transition structures have been explained on the basis of NBO analysis. q 2005 Elsevier Ltd. All rights reserved. 1. Introduction The Diels–Alder (DA) reaction is perhaps the most widely used synthetic methodology for the construction of six- membered rings. 1 The reaction is accompanied by several striking features such as high regioselectivity and endo- stereoselectivity, which have been rationalised on the basis of orbital symmetry 2 and theoretical calculations. 3,4 During the last few years the synthetic utility of the DA reaction has been expanded significantly by the use and the development of a wide variety of dienes and dienophiles. 5 The scope of this reaction has been further extended to the organophos- phoruscompounds bearing theOC]P– functionality, namelyphosphaalkenes, 6–8 heterophospholes including anellated azaphospholes 9–14 and phosphinines. 15 Many of these compounds undergo DA reaction much more readily than across the OC]C! moiety present in the non- phosphorus analogues with high regio-and stereoselec- tivities.This fact hasbeen rationalised on the basis of theoretical calculations, which indicate that the presence of a two-coordinate phosphorus atom (s 2 ,l 3 -P) in a DA reactant lowers the activation energy relative to that of the hydrocarbon system due to the weaker OC]P– p-bond compared to the OC]C! p-bond. 16,17 In the azaphosphole system, both the phosphorus and the carbonatom of the OC]P– functionalityrepresent prochiral centres and DA reaction on this moiety leads to the generation of two stereogenic centres in one step. The results,however, indicate that these reactions normally proceedwith completediastereoselectivity and regio- selectivity. We recently reported the stereo- and regio- selective DA reactions of 1,3-azaphospholo[5,1-a]- isoquinolineand -[1,5-a]pyridine 18–20 and also of thia- zolo[3,2-d][1,4,2]diazaphospholes and related com- pounds. 21 All these reactions occurred with complete endo stereoselectivity. The reactions with isoprene proceeded with complete regioselectivity as well, the regioisomer having phosphorus and methyl group in 1:3 positions bein formed as the sole product, except in one case when the other regioisomer was also produced in minor amount. 21 These results are in conformity with the DA reactions of 1H-1,3-benzoxaphosphole 22 and 2-acetyl-1,2,3-diaza- phosphole 23,24 reported earlier. We have reported the synthesis of [1,4,2]diazaphospholo [4,5-a]pyridines and their3-ethoxycarbonyl derivatives through [3C2]cyclocondensation 25 and [4C1] cyclo- condensation, 26 respectively. We have now investigated theirDA reactionswith 2,3-dimethylbutadiene and iso- prene.As observed earlier, 21 the presence of a second nitrogen atom (s 2 ,l 3 –N) in the azaphosphole ring enhances the reactivity of the OC]P– functionality and it undergoes DA reaction, even in the absence of an oxidizing agent. Th resulting phosphinines are, however, very sensitive toward 0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2005.08.045 Tetrahedron 61 (2005) 10521–10528 Keywords:Diels–Alderreaction;Azaphospholes; Diastereoselectivity; Regioselectivity; DFT calculations. * Corresponding author. Tel.: C91 1412701868; fax: C91 1412652730; e-mail: rajbns@yahoo.com