Study On The Reformatsky Reaction Catalyzed By N-Heterocyclic Carbenes

Reformatsky reaction is an important reaction to construct carbon-carbon bond,can be effectively synthesize β-hydroxy ester and derivatives thereof, forbio-pharmaceutical intermediates. However, there are still some problems in theapplication of the classical reaction, for the use of chemical equivalents of the metalreagent, products non-selective dehydration, low chemical yield and poorstereoselectivity. Therefore, the development of effective catalyst for Reformatskyreaction is an urgent need. As an important class of small organic molecules catalyst,N-heterocyclic carbene has been widely used in the reaction of formingcarbon-carbon bond by the polarity reversal. Here, we will report our initial researchof N-heterocyclic carbene catalyzed Reformatsky reaction.1. N-Heterocyclic carbene can efficiently catalyze the reaction of Si-Reformatsky.Exists of only0.5%of the nucleophilic carbene, N,N-dimethyl acetamide as a solvent,at room temperature, the aldehyde can be smoothly reaction with α-trimethylsilylethyl acetate, high yield obtained β-hydroxy ester. In the same reaction conditions,α-trimethylsilylacetone and α-trimethylsilylacetamide can also take part in thereaction, to β-hydroxy ketones and β-hydroxy amide in moderate yield. On this basis,we have proposed the corresponding catalytic mechanism.2. N-Heterocyclic carbene can be efficient catalytic reaction between aldehydeand ethyl-trimethylsilicon propiolate. Exists of only5%of the nucleophilic carbene,dichloromethane,-20°C, most of the aromatic aldehyde can occur in a tandemreaction, to give the corresponding product in high yield. With a substituent in ortho-position, a donating group in prara-positionand fatty aldehydes, alkynylation reactionoccurs, to obtain a high yield of trimethyl protected or deprotected alkynyl alcoholsproduct.Summary, a new method was developed based on small organic moleculescatalyst (NHCs), catalytic synthesis of β-hydroxy ester; and found a new N-heterocyclic carbene catalyzed tandem reaction between silicon reagent and aldehyde.This method is simple to operation, easy to get raw materials, friendly to environment,and with high yield.