Asymmetric Flow Reactions Catalyzed by Immobilized Diphenylprolinol Alkyl Ether: Michael Reaction and Domino Reactions

Abstract

Flow reactions using an immobilized diphenylprolinol alkyl ether catalyst 2 were investigated in three reactions of α,β‐unsaturated aldehydes and nitroalkanes such as nitromethane 3, nitroethanol 10, and nitroalkane 11, bearing two carbonyl groups. Whereas reactions using the corresponding monomer catalyst diphenylprolinol silyl ether 1 were slow, fast reactions were found with the immobilized polymer catalyst 2 in a batch system, and the latter was then applied to a flow system. In the Michael reaction of nitromethane 3, the polymer catalyst showed high reactivity in the initial 30 h and then decreased gradually. Good overall yield (72%) and turnover number (TON, 495) were obtained for a 60 h flow reaction, and the enantioselectivity of the product was excellent throughout. The TONs of domino reactions of nitroethanol 10 and nitroalkane 11, with two carbonyl groups, were 48 and 81, respectively.

An enantio- and diastereoselective approach to indoloquinolizidines in continuous flow

“…2). 15 Some of these immobilized species have shown their suitability for use in continuous flow and, among them 8g , formally derived from cis -4-hydroxyproline, 16 offers the important sustainability advantage of allowing work in continuous flow under solventless conditions. With the use of this catalyst, a variety of Michael-type adducts en route to enantiomerically pure important drugs (Paroxetine, Baclofen, Phenibut, Fluorophenibut, Rolipram) having been prepared.…”