Studies on the use of ¥á-hydroxyacids in Diels-Alder reactions of alkenylboronates

GRIMBLAT, N.N.; SAROTTI, A.M.; PISANO, P.L.; PELLEGRINET, S.C.

San Pablo

Congreso; São Paulo School of Advanced Science on Natural Products, Medicinal Chemistry and Organic Synthesis; 2011

Boron activated dienophiles are synthetically attractive due to their versatility. Although alkenylboronates are more stable than alkenylboranes, they are less reactive and harsh conditions are needed to carry out their Diels-Alder reactions.(1) Recently, we reported the microwave-assisted Diels-Alder reactions of vinylboronates in excellent yields and short reaction times.(2) In the past years, it has been shown that chiral diols can catalyse a number of addition reactions of boronates.(3) Encouraged by these results, we previously tested if biphenols could catalyse the Diels-Alder reaction between dibutyl vinylboronate and cyclopentadiene. However, no appreciable catalytic activity and enantioselectivities were observed. More recently, the conjugate addition of alkenylboronates to enones catalysed by a O-monoacyltartaric acid was reported.(4) For that reason, we have investigated the effect of the addition of ¥á-hydroxyacids to the reaction under study. Since dibutyl boronate cycloadducts are prone to hydrolysis, Diels-Alder products were subsequently oxidized with alkaline peroxide to 5-norbornen-2-ol. We tested several structurally different ¥á-hydroxyacids (glycolic acid, lactic acid, mandelic acid, malic acid and tartaric acid). We initially tried the use of catalytic and stoichiometric amounts of mandelic acid either at room temperature or with conventional heating, having encouraging results in terms of reaction times and yields. We later optimised the reaction conditions using microwave irradiation and different alcohols as additives. Best yields were obtained with 1 equivalent of (S)-mandelic acid and 1.7 equivalent of t-butanol under mild microwave irradiation in dichloromethane (93% in 2 h at 70 ¨¬C, endo/exo 60:40). Under the same conditions, 30 mol% of optically pure mandelic acid gave 64% yield and identical endo/exo ratio, which proves that the reaction can be catalysed although the catalytic activity is low. Unfortunately, poor enantiomeric excesses for both products were observed in all cases, particularly for the exo diastereoisomer (less than 22%).(5) At present we are trying to find a rationale to explain the experimental results. Preliminary 1H NMR studies suggest that a ligand exchange process occurs.