R 1 R 2 B(OCy) 2 1 R 2 O B R 1 OCy ( ) n R 3 OH R 3 3 2 ( ) n ∆ (i) transesterification (ii) [4 + 2] (i) HB(Cy) 2 , Me 3 N(O) a OH OH H ( ) n OH OH 5 H 6 + 4 R 1 R 1 (ii) Dienophile, ∆ b (iii) [O] c ( ) n OH OH OH OH OH Ph OH EtO 2 C OH Ph OH OH OH Ph 190 48 60 f 40 : 60 190 48 40 50 : 50 190 5 82 55 : 45 190 120 71 89 : 11 190 6 75 95 : 5 80 16 0.5 62 190 85 : 15 24 70 150 84 : 16 25 : 75 36 190 g 77 50 1 2 3 4 5 7 8 9 10 190 12 68 27 : 73 6 Diels–Alder reactions of dienylboron compounds with unactivated dienophiles: an application of boron tethering for substituted cyclohexenol synthesis Robert A. Batey,* Avinash N. Thadani and Alan J. Lough† Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6. E-mail: rbatey@alchemy.chem.utoronto.ca Received (in Corvallis, OR, USA) 7th December 1998, Accepted 27th January 1999 An efficient tethered intramolecular Diels–Alder reaction of 1,3-dienylboronates with various allyl and homoallyl alco- hols under thermal conditions is described. The use of Diels–Alder reactions is one of the most commonly encountered strategies for the formation of six-membered rings, particularly in natural product synthesis. 1,2 The reaction has been further augmented by using synthetic equivalents of either the diene or dienophile. 1 For instance, alkenylboron dienophiles have been used as synthetic equivalents to enols. 3–5 1,3-Die- nylboronates are versatile synthetic equivalents for hetero- subsituted dienes, since the allylboronate cycloadducts can be transformed to desirable substituted cyclohexene derivatives. 6 However, a major impediment to the use of 1,3-dienylboronate dienes in Diels–Alder reactions is the need for activated dienophile partners (e.g. N-phenylmaleimide or methylacry- late). Narasaka has demonstrated that phenylboronic acid can be used to create a temporary O–B–O tether between a diene and dienophile containing free hydroxy groups. 7 Inspired by Narasaka’s work, we reasoned that tethering 8–10 via a C–B–O connection would enable the reaction of 1,3-dienylboron compounds with dienophiles containing hydroxy groups, such as allylic and homoallylic alcohols (vide infra). Here we report the first examples of Diels–Alder reactions of 1,3-dienylboron compounds with unactivated dienophiles. Tethering of dienylboronate precursors 1 to a dienophilic component 2 allows in situ formation of mixed boronic esters, followed by intramolecular Diels–Alder reaction to the allyl- boracycles 3 (Scheme 1). Oxidation of the C–B bond in the adducts 3, with retention of stereochemistry, leads to the formation of cyclohexenols, which are valuable precursors in natural porduct synthesis. Overall, 1 acts as a masked 1-hydroxydiene equivalent in the Diels–Alder reaction. In comparison to existing silicon-tethered Diels–Alder method- ology, this approach uses the more readily synthesized dienylboronates as precursors. The use of a C–B–O rather than an O–B–O tether 7 is important, since in most cases O–B–O tethers are not applicable. The dienylboronates 1 are formed via standard hydroboration methodology from the corresponding enynes. Thus, hydro- boration of 4 and 7 with dicyclohexylborane afforded the corresponding dicyclohexyl(dienyl)boranes. The boron–cyclo- hexyl bonds were then preferentially oxidized with Me 3 N(O) to afford the desired dienylboronate (Table 1 and 2) without concomitant oxidation of the boron–diene bond. 6a,11 Since dienylboronates are subject to disproportionation, they were generally used in situ without purification. Thermal Diels– Alder reaction was conducted in the presence of an appropriate dienophile, in a degassed toluene solution, with 5 mol% of 2,6-di-tert-butyl-4-methylphenol (BHT) as a free radical in- hibitor, using a sealed tube and a heating bath of the appropriate temperature. Oxidation with Me 3 N(O) or basic H 2 O 2 then afforded racemic cyclohexene diols 5 and 6 in good yields (Tables 1 and 2). The constraining effects of the tether both accelerate the rate of cycloaddition, and control the regio- and stereoselectivity of the reaction. We have not been able to isolate cycloadducts in those cases where the initial tethering step cannot occur. For instance, no cycloaddition reaction was observed between ethane-1,2-diyl dienyl boronates and cinnamyl alcohol, allyl alcohol or methyl cinnamyl ether, even after prolonged heating at 220 °C. † To whom correspondence concerning the crystallographic data should be addressed. Scheme 1 Table 1 Tethered Diels–Alder reactions of 4 Yield Entry Dienophile T/°C t/h (%) d Dr (5 : 6) e a 1 equiv. HB(Cy) 2 , THF, 0 °C to room temp., 1 h; 2 equiv. Me 3 N(O), THF, 0 °C to room temp., 2 h. b [Boronate] = ca. 0.3 m, PhCH 3 , 5 mol% BHT. c 5 equiv. Me 3 N(O), C 6 H 6 , 80 °C, 24 h or 3 equiv. NaOH/3 equiv. H 2 O 2 , THF–H 2 O, 2 h. d Yields are for chromatographically purified material and are calculated from 4. e The diastereomeric ratios (5 : 6) are based upon NMR analysis of the crude products. f 6% of the corresponding enone was isolated. g Only 5 was isolated along with 6% of a byproduct presumably derived from 6. Chem. Commun., 1999, 475–476 475