Imino esters stereoselectivity

We were particularly interested to see whether a regio- and stereoselective hy-droxyalkylation and amrnoalkylation of 1 and 2 with aldehydes and imino esters, perhaps by choice of the substituent X at the Ti atom, with formation of the corresponding sulfonimidoyl-substituted homoallyl alcohols 4-7 and the homoallyl amines 8-11 (Fig. 1.3.3) could be achieved. Reggelin et al. had already demonstrated that the sulfonimidoyl-substituted mono(allyl)titanium complexes 3, the... 

It is noteworthy that stereoselectivities were high, even with sterically demanding substituents at the double bond. Similarly, the treatment of the cyclic bis (allyl) titanium complexes 18 with the imino esters 23a-c afforded the corresponding B-syn-configured cyclic unsaturated amino acid derivatives -25 and the Z-syn-configured isomers Z-25 with >98% regioselectivity and >98% diaste-reoselectivity in good yields. 

In the area of [3 + 2]-cycloadditions (1,3-dipolar cycloadditions), chiral silver catalysts have been utilized extensively for the enantioselective formation of five-membered rings from prochiral substrates. For example, Zhang and co-workers360 have reported the highly enantioselective Ag(i)-catalyzed [3 + 2]-cycloaddition of azomethine ylides to electron-deficient alkenes. Thus, reaction of ct-imino esters 442 with dimethyl maleate in the presence of catalytic amounts of silver(i) acetate and the chiral bisferrocenyl amide phosphine 443 provided the chiral pyrrolidines 444 with high stereoselectivities and chemical yields (Scheme 131). Only the endo-products were isolated in all cases. 

Azomethine ylides are very important 1,3-dipoles, and they are usually used to react with alkenes leading to the formation of the highly substituted pyrrolidine derivatives [17]. A novel and practical process for the 1,3-dipolar cycloaddition of azomethine ylides with alkenes had been reported by j0rgensen and coworkers [18]. They proposed that a dipol-chiral base ion pair would be generated between a-imino ester-metal complex and a cinchona alkaloid, and subsequent cycloaddition with dipolarophile would take place in a stereoselective manner (Scheme 10.13). 

Ooi and Maruoka developed an efficient phase transfer catalyst (46a-e), which consisted of chiral N-spiro ammonium salts with binaphthalene skeleton. 3,3 -(3,4,5-Trifluorophenyl)ammonium salt (46e) provided a perfect stereoselection in benzylation of benzophenone Schiffbase of glycine terf-butyl ester (47) (Scheme 5.13, Table 5.5) [19]. The perfect stereoselective alkylation is applicable for a variety of alkyl bromides in the presence of 1 mol% of the catalyst (46e). Not only monoalkylation but also the consecutive double alkylation of 49 was successful to give 50 in excellent enantioselectivities (Scheme 5.14) [20]. The protocol is useful for the enantioselective aldol reaction of 47 with aldehyde (51) [21] and a-imino ester [22], in which catalysts (46f) and (46g) were effective (Scheme 5.15) [23]. 

Wang and coworkers reported that pyrrolidine-sulfonamide 3a is an excellent catalyst for the Mannich reaction of ketones with an a-imino ester. The Mannich reaction of various ketones with AT-PMP-protected a-imido ethyl glyoxylate was completed within 2 h at ambient temperature in the presence of catalyst 3a (10 mol%). The desired Mannich adducts were obtained in high chemical yields and with high stereoselectivities (Scheme 9.38). 

On the other hand, the Gong group reported the enantioselective [l,5]-hydride transfer/cyclization reaction between ortho tertiary amine substituted aromatic keto esters 33 and aromatic amines 34 catalyzed by chiral bisphosphoric acid (1 ,1 )-C8, developed in their own group (Scheme 4.16). In this reaction, the in situ formed a-imino esters 36 act as the hydride acceptors, allowing the efficient synthesis of cyclic aminals 35 in high stereoselectivity (up to 14 1 dr, 90% ee). 

To improve upon the selectivity of the ketimine reduction process further, the hydrosilylation of a range of substrates derived from (/ )- -phenylethylamine were examined [37]. Optimization of the reaction conditions allowed obtaining complete diastereoselective reduction of a wide range of acetophenone-derived ketimines as well as a-imino esters, demonstrating the cooperative effect of catalyst and the (/ )-methyl benzyl residue at the imine nitrogen. In this context, we reported also a low cost protocol for a highly stereoselective reduction of ketimines bearing a very cheap and removable chiral auxiliary, promoted by an achiral inexpensive Lewis base, such as DMF [38]. 

Azetidine-2-carboxylic acid (2) is commercially available. It is readily prepared as the racemate by refluxing 2,4-dibromobutyric acid ester with benzhydrylamine in acetonitrile. If benzyl 2,4-dibromobutyrate is treated with benzhydrylamine, the resulting benzyl TV-benz-hydryl-D,L-azetidine-2-carboxylate is hydrogenolytically processed to D,L-azetidine-2-car-boxylic acid in a one-step reaction. 101,107 Resolution of the racemate can be performed by the method of Vogler 108 via fractional crystallization of the Z-D,L-Aze-OH-H-Tyr-N2H3 salt thereby the salt of the D-imino acid precipitates first from methanol. 96 A stereoselective synthesis of A-tosyl-L-azetidine-2-carboxylic acid can be achieved by a two-step reaction from N-tosyl-L-homoserine lactone. 94 ... 

The 1,3-dipolar cycloaddition of nitrile oxide to an unsaturated ester is a useful synthetic strategy for the synthesis of heterocycles such as A -isooxazolines and a-hydroxy-y-keto or y-imino carboxylic acids. Thus, the 1,3-dipolar cyclo-addition of the 4-0-acryloyl derivative 115 (R = f-butyldimethylsilyl) with two nitrile oxides (R = Ph or t-Bu) was explored by the Tadano group [95] (O Scheme 33). In the case of benzonitrile oxide (R =Ph), a functionalized A -isooxazoline 124 was obtained as a single isomer in excellent yield. Thus, the cycloaddition proceeded smoothly at room temperature with extreme stereoselectivity. 

The hydroboration of alkenes and alkynes to highly chemo-, regio-, and stereoselective alkyl and vinyl boronic esters with pinacolborane is catalysed by bis(imino)pyridine Fe(II) complex with activating agent tolylMgBr in THF. Preliminary mechanistic experiments suggest that an Fe(I) catalyst may be formed under the reaction conditions. ... 

A highly stereoselective synthetic strategy for disubstituted piperidines 247 with cis appendages was reported recently. A one-pot intermolecular imino aldol reaction of a-arylmethylidine 244 or a-alkylidine p-keto ester 248 with aldimine 246 followed by intramolecular aza-Michael reaction (alkylative cyclization) in a domino fashion afforded the corresponding piperidines 247 in high yields and excellent stereoselectivity (er, dr >99%) (Scheme 40.54). ... 

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