Cyanation enantioselective

In addition to this, asymmetric 1,3-dipolar cyclization reactions of nitrones with olefins,40 41 catalytic enantioselective cyanation of aldehydes,42 catalytic enantioselective animation,43 and aza-Michael reactions44 have been reported, and high enantioselectivities are observed. 

Lundgren, S. Wingstrand, E. Penhoat, M. Moberg, C. Dual Lewis acid-Lewis base activation in enantioselective cyanation of aldehydes using acetyl cyanide and cyanoformate as cyanide sources. J. Am. Chem. Soc. 2005,127, 11592-11593. 

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

Finally, several examples of only moderately effective (<75% ee) catalytic enantioselective cyanation of benzaldehyde derivatives have been reported recently [32-37],... 

Nakamura, S., Sato, N., Sugimoto, M., Toru, T. A new approach to enantioselective cyanation of imines with Et2AICN. Tetrahedron Asymmetry 2004, 15,1513-1516. 

Optically pure cyanohydrins serve as highly versatile synthetic building blocks [24], Much effort has, therefore, been devoted to the development of efficient catalytic systems for the enantioselective cyanation of aldehydes and ketones using HCN or trimethylsilyl cyanide (TMSCN) as a cyanide source [24], More recently, cyanoformic esters (ROC(O)CN), acetyl cyanide (CH3C(0)CN), and diethyl cyanophosphonate have also been successfully employed as cyanide sources to afford the corresponding functionalized cyanohydrins. It should be noted here that, as mentioned in Chapter 1, the cinchona alkaloid catalyzed asymmetric hydrocyanation of aldehydes discovered... 

Moberg and coworkers also achieved the highly enantioselective cyanation of aldehydes by using the dual activation concept (Table 4.5) [30]. It is known that the Lewis acidic dimeric salen-Ti complex 8 catalyzes the cyanation of benzaldehyde with... 

Scheme 4.10 Enantioselective cyanation of aldehydes with cyanoformic esters catalyzed by (S)-ALB (7) and cinchonine.

Table 4.5 Dual Lewis acid-Lewis base activation in enantioselective cyanation of aldehydes using acetyl cyanide.

Acetone cyanohydrin 97 was used as a cyanide ion source by Herrera and Ricci to accomplish the phase-transfer enantioselective cyanation of in situ-generated... 

It is remarkable that Danda reported enantioselective autoinduction in asymmetric cyanation. When a small amount of the optically pure cyanohydrin was added to the reaction mixture, highly enantioselective cyanation occurred even by using almost racemic catalyst 5, Fig. 1 (2% ee) [32]. 

The bifunctional catalysts developed by Shibasaki and coworkers effective in the asymmetric cyanation of aldehydes and ketones (see Section 6.2) have been applied to good effect in the cyanation of imines. For instance, aluminium BINOL (6.65) catalyses the cyanation of aromatic and a,p-unsaturated N-fluorenylaldimines using TMSCN in good ee, while gadolinium complexes of the glucose-derived ligand (6.71) and derivatives have been used in the enantioselective cyanation of ketimines. ... 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

Scheme 6.19 Enantioselective cyanation/Brook rearrangement/C-acylation of acylsilanes catalyzed hy chiral metal alkoxides.

Tridentate chiral Schiff bases derived from (- -)-Q -pinene (123) catalyse enantioselective addition of diethylzinc to aryl aldehydes. Steric, aryl stacking, and electronic effects are significant in the transition state, the latter being probed by a Hammett plot of ee versus for a series of benzaldehydes. Complexes of the Schiff base (123) with titanium(IV) catalyse enantioselective cyanation. ... 

A multicomponent bifunctional catalytic system based on a titanium complex was also used for the efficient enantioselective cyanation of aldehydes with ethyl cyanoformate [221]. The catalyst was readily prepared by the reaction of Ti(O Pr)4 with (S)-6,6 -Br2BINOL in combination with cinchonine and (lR,2S)-(—)-N-methylephedrine. As shown in Scheme 14.91, the optimized catalyst combination (10 mol%) promotes the reaction smoothly to afford the desired cyanohydrins ethyl carbonates in moderate to excellent isolated yields (up to 95%) with high enantioselectivities (up to 94% ee). Although the mechanistic aspects... 

Sansano reported the enantioselective cyanation of aldehydes with benzoyl cyanide using BINOLAM-Ti(IV) complex as a catalyst without the presence of additives, good chemical yields and moderate enantioselectivities of the reaction have been achieved (Scheme 14.92) [222]. The Lewis basic side chains at 3,3 -positions of BINOL ligand are believed to play an important role and a bifunctional mechanism has been proposed. 

We developed various catalytic enantioselective cyanation and azidation reactions using chiral poly rare earth metal (RE) complexes derived from ligands 5-8 and TMSCN or TMSN3 as a stoichiometric nucleophile [43, 44]. General mechanism for those asymmetric catalyses is shown in Scheme 11. First, polymetallic complexes 9 containing defined higher order strucmres are generated via a reaction... 

Figure 3-6. Chiral catalysts for enantioselective cyanation of aldehydes.

Table 3-9. Enantioselective cyanation of Qr,y0-unsaturated carbonyl compounds.

In 2001, Feng et al. reported chiral 7V-oxides 110-112 for the enantioselective cyanation of aldimines [125-127], The yields (63-93%) are good, but enantioselec-tivities (37-73%) are still modest [125]. After optimization of the reaction conditions, however, up to 97% ee could be achieved (Scheme 7.19) [126,127],... 

Scheme 7.19 Enantioselective cyanation of aldimines catalyzed by chiral iV-oxides 110-112...

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