Highly Efficient Organosuperbase-Catalyzed Mannich-type Reactions of Sulfonylimidates with Imines: Successful Use of Aliphatic Imines as Substrates and a Unique Reaction Mechanism

摘要

A base-catalyzed reaction that forms a carbon-carbon bond by proton transfer is an ideal reaction for constructing basic molecular skeletons from the point of view of atom economy. Over the past decade, several base-catalyzed reactions, including asymmetric transformations, have been intensively studied. However, available substrates for nucleophilic carbanion formation by deprotonation have been limited to those bearing relatively acidic hydrogens; catalytic activation of substrates with less acidic hydrogens remains difficult. One typical example of a less reactive substrate is an ester without any activating group in the a-position. We have recently developed a reactive ester equivalent, a sulfonylimi-date, and successfully applied it to Mannich-type reactions with imines in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0.]undec-7-ene (DBU) or an alkali earth metal alkoxide or amide, and obtained the desired adducts in good yields and with high stereoselectivities. However, catalyst activity was not sufficient for achieving high catalyst turnover number (TON) or turnover frequency (TOF), and substrates were limited to aromatic imines. In many cases, the reactions of aliphatic imines are sluggish owing to rapid isomerization to enamine forms under both basic and acidic conditions.