Enantioselective Reissert-Type Reaction

The Reissert-type reaction is considered to proceed via two steps (i) the generation of an acyl quinolinium intermediate by a nucleophilic attack of quinoline to an acid chloride and (ii) the addition of cyanide [150]. Shibasaki has developed an 

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When first reported in 1905, the Reissert reaction demonstrated the addition of KCN to quinoline in the presence of benzoyl chloride, but many new modifications since then have employed other nucleophiles and catalytic promotion by a Lewis acid. Shibasaki reported in 2001 the first catalytic enantioselective Reissert-type reaction. Optimized reaction conditions involving an electron-rich aromatic acid chloride in a low-polarity solvent, and use of catalyst 14, were found to suppress the racemic pathway and resulted in good enantioselectivity (Scheme 2) <2001JA6801>. 

Elaboration of isoquinoline derivatives in asymmetric fashion was examined as well in 2001. In a manner similar to that described in section 6.1.3.2, an enantioselective Reissert-type reaction was utilized to construct a chiral, quaternary center at the Cl position of isoquinoline derivatives. For example, treatment of isoquinoline 85 with vinyl chloroformate and TMSCN in the presence of bifunctional catalyst 86 afforded isoquinoline derivatives such as 87 in up to 95% ee. The effect of the R group at the 1-position and the catalyst counterion were detailed. 

The first example of a catalytic enantioselective Reissert-type reaction with electronically tuned bifunctional catalyst 43 as the catalyst was accomplished by the Shibasaki group in 2001 (Scheme 19.52). A broad range of 1-substituted isoquinolines underwent the Reissert-type reaction well, giving the corresponding adducts with chiral quaternary stereocentre in 73-95% enantiomeric excess. 

Asymmetric acylcyanation of quinolines (Reissert-type reaction) with 2-furoyl chloride and TMSCN is successfully performed by using the chiral catalyst 168 (Scheme 10.243) [658]. In this reaction the sterically more demanding complex 168b exceeds 168a in enantioselectivity. 

Addition to Carbonyls, Imines (Strecker-type Reactions), and Heteroaromatic Rings (Reissert-type Reactions). Cyanohydrin trimethylsilyl ethers are of significant synthetic interest as they can be transformed into a variety of multifunctional intermediates. Aldehydes and ketones can be enantioselectively converted to cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of a Lewis acid and a chiral ligand. Enantioselective and/or diastereoselective formation of cyanohydrins and their derivatives has been reported and most of these reactions involve chiral ligands and metal catalysts containing Ti (eq 24), Sm (eq 25), and A1 (eq 26). ... 

Catalysts (25) are the Lewis acid-Lewis base bifunctional catalysts in which Lewis acid-Al(III) moiety activates acyl iminium ion and the Lewis base (oxygen of phosphine oxide) does TMSCN, simultaneously (Scheme 5.7). Halogen atoms at the 6-position enhanced both yields and enantioselectivity in Reissert-type cyanation of the imino part of 26. However, the order for the activation is not parallel to the electronegativity of the halogen atoms and, moreover, the strong electron-withdrawing trifluoromethyl group provided unexpectedly the worst result for the activation [13]. It is not simple to explain this phenomenon only in terms of the increased Lewis acidity of the metal center. Trifluoromethylated BINOL-zirconium catalysts (28) for asymmetric hetero Diels-Alder reaction (Scheme 5.8) [14], trifluoromethylated arylphosphine-palladium catalyst (32) for asymmetric hydrosilylation (Scheme 5.9) [15], and fluorinated BINOL-zinc catalyst (35) for asymmetric phenylation (Scheme 5.10) [16] are known. 

Other type of Lewis acid derived by a 1 2 mixture of Et2AlCl and chiral bifunctional ligand (69) having sulfoxide moiety as Lewis base site was found as an excellent catalyst for catalytic enantioselective Reissert reaction of nicotine amides (70) (Scheme 6.52) [67]. On the basis of ESI-MS studies, active catalyst species has... 

The Reissert reaction of quinoline of MesSiCN/RCOCl can be conducted in an enantioselective fashion in the presence of a chiral BINAP-based catalyst to give enantiomeric nitriles of type 23 [91]. The Reissert compounds 23 are hydrolysed in an acid medium giving aldehydes and quinoline-2-carboxylic acid 24 ... 

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