The 1-Phenylsulfonylallenyl Terminus in Intramolecular Diels-Alder Reactions: Tether Length and Reactivity

Abstract

Methods are described for the synthesis of 1-phenylsulfonylalka-1,2,(n + 4),(n + 6)-tetraenes 5 (n = 2 -4), and preliminary findings on their thermally-induced intramolecular cycloaddition behaviour are reported. The reaction of 5 (n = 4) is slow, and engages the unactivated π-bond, whereas those of 5 (n = 2 & 3) proceed readily and exo-selectively with dienophilic participation of the activated terminal π-bond, to give the expected [4 + 2] cycloadducts. The reactivity of 5 (n = 2) is particularly noteworthy since cycloaddition proceeds under exceptionally mild conditions. The well-known advantages of intramolecular Diels-Alder (IMDA) reactions for assembling complex ring systems 1 continue to promote the development and application of new methodology. Recently, there have been several reports 2 on the use of the allenyl functionality as the dienophilic partner in IMDA methodology, but hitherto, with little evidence of emergence of a general pattern of structure-reactivity and selectivity.As part of our programme of investigation into the dienophilic utility of variously functionalised allenes, 3 we report the preliminary findings resulting from synthesis and IMDA reactions of 1-phenylsulfonylallenyl compounds, terminally substituted with appropriate butadienyl functionality. In the first phase of this investigation, we set out to establish the levels of intramolecular cycloaddition reactivity and periselectivity associated with variations in the tether length between the participating 1-phenylsulfonylallenyl and butadienyl termini. The C 9 -C 11 model systems were thus chosen, in the reasonable expectation that they would accommodate favourable transition state geometries for this purpose, and would be expected to yield functionalised bicyclic cycloadducts of synthetic utility.The starting (E)-alka-(n + 2),(n + 4)-dien-1-ols 1 (n = 2 -4) were prepared in accordance with standard literature methods. 4 -7 Swern or Dess-Martin 8 oxidation of 1 furnished the corresponding aldehydes 2, which were ethynylated to give the dienynols 3 in good to moderate yields (Scheme 1). Treatment of these intermediates at -78 °C with benzenesulfenyl chloride readily resulted in formation of the 1-phenylsulfinylallenyl dienes 4, via [2,3] sigmatropic rearrangement of the primary phenylsulfenyl esters. 9 Oxidation of the sulfoxides 4 with m-CPBA proceeded smoothly and, generally, chemoselectively at 0 °C to give the corresponding 1-phenylsulfonylalka-1,2,(n + 4),(n + 6)-tetraenes 5. With one exception (5c; see below), these were stable products which were fully characterised. 10 The E/Z ratios of 5a,b and d were in excess of 95 % and reflect those of the precursors 1. Scheme 1. (a R = H, n = 4; b R = H, n = 3; c R = H, n = 2; d R = Me, n = 2) Reagents. (i) (COCl) 2 , DMSO, CH 2 Cl 2 , NEt 3 , -60 °C; (ii) HCCMgBr, THF, 20 °C; (iii) PhSCl, NEt 3 , CH 2 Cl 2 , -78 °C; (iv) m-CPBA, CH 2 Cl 2 , -0 °C Intramolecular cycloadditions of 5a and 5b were conducted in toluene (sealed tube) at temperatures which were determined by reasonable rates ...