z Catalysis Enantioselective Addition of Cyanide to CF 3 -Substituted Alkylidenemalonates: Construction of Trifluoromethylated All-Carbon Quaternary Stereocenters Ajay Jakhar, [a, b] Mohd Nazish, [a, b] Naveen Gupta, [a, b] Noor-ul H. Khan,* [a, b] and Rukhsana I. Kureshy [a, b] The construction of a new class of chiral organofluorine compounds with an all-carbon stereocenter bearing a CF 3 group was disclosed. The cinchona alkaloid based phase transfer catalyzed asymmetric conjugated cyanation of CF 3 substituted alkylidene malonates have been developed. The nitrile products were achieved in excellent yield with good enantioselectivity. The chirality of product increased up to 98% by recrystallization. Introduction Organofluorine compounds have an integral role and increas- ing attention in pharmaceuticals, agrochemicals, materials, and fragrances industries. [1,2] More than 20% of drugs and around 35–40% of agrochemicals are organofluorine com- pounds since fluorine containing organic molecules exhibit unique properties and has a profound effect on the biological activities of these compounds. [3,4] Undoubtedly, this remark- able utility triggers the synthetic chemist to focus on the development of new strategies for the enantioselective syn- thesis of fluorine containing organic moieties. Along with the growing need for organofluorine compounds, construction of all-carbon quaternary stereocenter bearing CF 3 group in a reliable and effective fashion have become a burgeoning research area. There are two major pathways disclosed to construct fluorine containing compounds, first is the introduc- tion of CF 3 group to prochiral center [5] and second, nucleo- philic addition to CF 3 bearing prochiral center [6] or 1,4 conjugated nucleophilic addition to CF 3 containing a,b- unsaturated compound (Scheme 1). [7] In this regard, for accessing this class of high-value all-carbon quaternary stereo- center containing compounds, preparation of the fluorinated pronucleophiles and their catalytic enantioselective C À C bond forming reactions attracted our attention. However, the enantioselective construction of all-carbon-substituted stereo- centers bearing CF 3 moieties are less explored and a challenging task. Moreover, asymmetric cyanation of activated alkenes such as a,b-unsaturated ketones, [7a,8] a,b-unsaturated imides, [9] a,b-unsaturated N-acylpyrroles, [10] a,b-unsaturated esters [11] and nitroalkenes [7e,12] are less studied in compared to the asymmetric cyanation of carbonyl [13] and imines. [13c,14] We recently demonstrated the synthesis of CF 3 substituted alkylidene malonates and its subsequent cyanation to con- struct quaternary carbon-center (Scheme 2). [15] The asymmet- ric cyanation of CF 3 substituted alkylidene malonates provides an efficient synthetic method for chiral b-aryl b-CF 3 -disubsti- tuted g-aminobutyric acids (GABA) and chiral nitrogen con- taining CF 3 substituted arylpyrolidine heterocyclic com- pounds, which are an important building block in the pharmaceutical and agrochemical industries. The nitrogen containing CF 3 substituted arylpyrolidine heterocyclic compounds are useful as a pest controlling agent. [16] By considering the advantage of this versatile synthon, herein, first time we are reporting the chiral phase transfer type catalyst for the conjugated asymmetric cyanation of CF 3 [a] Dr. A. Jakhar, M. Nazish, N. Gupta, Dr. N.-u. H. Khan, Dr. R. I. Kureshy Inorganic Materials and Catalysis Division, CSIR-Central Salt and Marine Chemicals Research Institute, G. B. Marg, Bhavnagar-364 002, Gujarat, India E-mail: khan251293@yahoo.co.in [b] Dr. A. Jakhar, M. Nazish, N. Gupta, Dr. N.-u. H. Khan, Dr. R. I. Kureshy Academy of Scientific and Innovative Research. CSIR-Central Salt and Marine Chemicals Research Institute, G. B. Marg, Bhavnagar-364 002, Gu- jarat, India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201800113 Scheme 1. Construction of quaternary stereocenters containing CF 3 group (a) Enantioselective introduction of CF 3 group to prochiral center, (b) Enantiose- lective nucleophilic addition to CF 3 bearing prochiral center, (c) Asymmetric conjugated nucleophilic addition to CF 3 containing a,b-unsaturated com- pound. Full Papers DOI: 10.1002/slct.201800113 4838 ChemistrySelect 2018, 3, 4838 – 4843  2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim