Imines N-Cbz

Three different highly enantioselective addition reactions of sulfones to in situ generated N-Boc and N-Cbz imines have been reported recently, all rmder PTC using structurally similar chiral ammonium salts as catalysts (Scheme 29.31). In 2007, Shibata, Toru, and coworkers developed a PTC reaction of imines, generated in situ from a-amido sulfones, with l-fluorobis(phenyIsulfonyl)methane (FBSM) [67]. A quinidine derived quaternary ammonium chloride (52) is used as catalyst, and the Mannich-type reaction proceeds smoothly to afford the 1-fluorobis(phenylsulfonyl)methylated amines in high yields and excellent enantioselectivities. Desulfonation of adducts by treatment with Mg in EtOH yields the monofluoromethylated adducts 55 with nearly complete retention of the enantiomeric excess [Scheme 29.31 (1)]. 

Ricci, Bernardi and coworkers demonstrated that asymmetric addition of aryl-sulfonylacetates to both N-Boc and N-Cbz imines can also be conducted very efficiently when using quinidine derivatives of type 53 and 54 as a catalyst [68]. These asymmetric Mannich-type reactions require toluene at -30 °C, aqueous K3PO4 as the base, and 10mol% of the quaternary ammonium salt for optimal... 

CBS (Corey-Bakshi-Shibata) catalyst 966 N-Cbz imines 866 centrifugal separation 802 ceric ammonium nitrate (CAN) 72, 1167, 1175... 

In the synthesis of hydroxamic acid 19a, having a free quaternary amino group (see Scheme 4.4), the intermediate sulfone 21 was synthesized by Pd-catalyzed reaction of phenol with p-bromo derivative 20 [24], Lithiation of 20, followed by nucleophilic addition to the A-Cbz imine of trifluoropyruvate 22 [25] afforded the a-CF3 a-amino acid derivative 23 in fair yields. Basic hydrolysis of the ester function gave the carboxylic acid 24, which was submitted to condensation with ()-15 n-hydroxylamine, affording hydroxamate 25. The subsequent hydrogenolysis of 25 afforded the target molecule 19a. 

In addition to chiral PTCs, cinchona-based thioureas have also been proved to serve as catalysts for nitro-Mannich reactions. In 2006, Ricci and coworkers first reported that the quinine-based thiourea 40 (20mol%) can catalyze the aza-Henry reaction between nitromethane and the N-protected imines 93 derived from aromatic aldehydes [40]. N-Boc-, N-Cbz-, and N-Fmoc protected imines gave the best results in terms of the chemical yields and enantioselectivities (up to 94% ee at —40°C) (Scheme 8.30). 

N-Boc-protected imines were also applicable to the diastereo- and enan-tioselective Mannich reaction of aliphatic aldehydes other than acetaldehyde. The highly q n-selective asymmetric Mannich reaction catalysed by L-proline was reported by List and coworkers in 2007. In contrast, (5)-3 promoted the antz-selective asymmetric Mannich reaction between aliphatic aldehydes and iV-Boc-protected imines and the catalyst loading could be reduced to 1 mol% without loss of stereoselectivity. By using N-Cbz-protected aminoacetaldehyde instead of simple aliphatic aldehydes, both syn- and antz-vicinal diamines were synthesised by simply changing the catalyst through the above-mentioned amine-catalysed Mannich reactions, respectively. ... 

Fluoropyruvaldehyde N,S-ketah (R)-32 can be prepared in good yields (up to 88%) and e.e. s (up to 82%) from a-(fluoroalkyl)-p-sulfmylenamines (7 )-2-19a-c (Scheme 9), through an unprecedented self-immolative tandem sequential process (34,35), consisting in a Pummerer reaction promoted by TFAA (.step 1) that provides the intermediate a-trifluoroacetoxy A -Cbz imine 36, followed by a 1,2-migration of the / -tolylthio group (step 2), triggered by addition of silica gel or aqueous base. 

This is one of the finest single-step transformations in the chemical literature. Note that five reactions are achieved in one pot hydrogenation of two double bonds, Cbz deprotection, intramolecular imine formation, and convex-face alkene hydrogenation that establishes the n-Pr stereocenter. 

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