Enantioselective Redox-Neutral Coupling of Allenylic Alcohols through Divergent Cooperative Catalysis

The past two decades have witnessed a magnificent growth of cooperative catalysis, where two substrates usually of complimentary polarity are activated independently by two different catalysts, before the reactive intermediates converge into the desired product. Different variants of cooperative catalysis have emerged since the inception of this concept and led to the discovery of innumerable transformations, which are difficult or impossible to achieve under a single catalyst. In this paper, we introduce the concept of divergent cooperative catalysis, which is fundamentally different from traditional modes of cooperative catalysis. Here, the reaction takes place with a single substrate, which is converted to two transient intermediates of complimentary polarity under the influence of two different catalysts. The combination of these two polarity-matched inter-mediates gives the desired product. Due to the use of a single substrate, the reactions under divergent cooperative catalysis are expected to minimize the complications associated with traditional cooperative catalysis. The proof of this concept is demonstrated by an enantioselective redox-neutral coupling of branched allenylic alcohols, cooperatively catalyzed by iridium and Lewis acid. In the Lewis acid-catalytic cycle, racemic allenylic alcohol is transformed into an alpha,beta-unsaturated enol (cross dienol) through Meyer-Schuster-type 1,3-hydroxy transposition. On the other hand, in an independent process, catalyzed by a combination of an Ir(I)/(phosphoramidite,olefin) complex and Lewis acidic Sc(OTf)3, allenylic alcohol is believed to produce an η2-Ir(I)-bound allenylic carbocation intermediate, which is intercepted by the in situ generated cross dienol. Overall, starting from stable and easily accessible branched allenylic alcohols, the process combines Lewis acid-catalyzed 1,3-hydroxy transposition with Ir-catalyzed enantioselective allenylic substitution to furnish alpha′-allenylic alpha,beta-unsaturated ketones, without using preformed carbon nucleophiles, in moderate to good yields generally with excellent enantioselectivities (up to >99.9:0.1 er). Detailed experimental and DFT studies helped shed light on the mechanism of the reaction, which revealed the initially formed bis-allenylic ether to be a substrate reservoir.