A theoretical study on Rh(I) catalyzed enantioselective conjugate addition reactions of fluoroalkylated olefins

Abstract

Catalytic asymmetric synthesis has gained great interest and practical usefulness in pharmaceutical, medicinal and agricultural fields. Among them, enantioselective synthesis of optically active fluoroalkylated compounds have an icreasing demand. Utilization of a chiral ligand like BINAP and a transition metal facilitates the synthesis of products by lowering the activation barrier.Upper parts of the BINAP are sterically hindered by the naphtyl groups which limit its rotation. The rigid structure of the catalyst plays a key role in determining the enantioselectivity of products. Although there are many attempts to clarify the enantioselectivity, origin of the stereoselectivity and the reaction mechanism are important subjects of research.In this study, the reaction mechanism and enantioselectivity differences observed in the rhodium catalyzed conjugate addition reactions of a series of aryl and alkene groups to fluoroalkylated olefin has been explored by quantum mechanical methods. Reaction of the various aryl boronic acids gives different yields and enantioselectivities. In the reaction conducted by Konno et al, which was carried out in 4:1 toluene:water environment, the optimum conditions were determined as by reacting 1.2 equivalent of phenylboronic acid with 5 mol % of [Rh(C8H12)2]BF4 and 6 mol % of (S) BINAP. Next, under the optimum condition the reactions of various arylboronic acids were subjected to investigation. para-chlorobenzene substituent gave excellent yield with excellent enantiomeric excess, whereas ortho-chlorobenzene substituent gave very little product. Besides, thiophene substituent gave excellent enantiomeric excess with good yield. On the other hand, styrene substituent was unsuccesful to give good enantiomeric excess.Firstly, a model mechanism has been devised in order to understand the effect of phenyl and naphtyl rings present on (S) BINAP. Thus, effective models are saught in order to decrease the computational times required in these calculations. In the second step, the whole system is studied where two steps reaction mechanism, proposed by experimentalists, have been followed. For this purpose, DFT calculations have been performed with the B3LYP functional with the 3-21G* and 6-31G* basis sets, utilizing Gaussian 09 program package. Density Functional methods are highly utilized in understanding the mechanisms along with regioselectivities and/or enantioselectivities observed in real transition metal catalyzed reaction systems. To account on the effect of solvent, single point calculations have been performed with various levels of theories.