Cyanation asymmetric

Scheme 5.32. Catal3Tic heterobimetallic asymmetric cyanation of aldehydes.

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

Scheme 5.34. Chiral base-catalyzed asymmetric cyanation of ketones.

Asymmetric Cyanation of C=N Bonds (Strecker-Type Reaction). . 121... 

Very few methods developed recently are applicable to the cyanation of not only electron-rich but also electron-deficient aromatic, as well as aliphatic aldehydes. Titanium(IV)-derived complex 1 (Fig. 1), reported by Uang, catalyzes the hydro cyanation of aromatic, a, 3-unsaturated, and aliphatic aldehydes with high enantioselectivity (>88% ee for all substrates reported) [15]. Similarly, Ti(IV)-catalyst 2 developed by Choi has proved to be highly enantioselec-tive for the cyanation of various classes of aldehydes (>90% ee for most substrates) [16]. Belokon and co-workers reported two chiral salen-based systems (salen)VO catalyst 3a and [(salen)TiO]2 3b, both of which provided moderate levels of enantioselection when applied to the asymmetric cyanation of diverse... 

The Strecker reaction [1] starting from an aldehyde, ammonia, and a cyanide source is an efficient method for the preparation of a-amino acids. A popular version for asymmetric purposes is based on the use of preformed imines 1 and a subsequent nucleophilic addition of HCN or TMSCN in the presence of a chiral catalyst [2], Besides asymmetric cyanations catalyzed by metal-complexes [3], several methods based on the use of organocatalysts have been developed [4-14]. The general organocatalytic asymmetric hydrocyanation reaction for the synthesis of a-amino nitriles 2 is shown in Scheme 5.1. 

For selected excellent contributions of metal-catalyzed asymmetric cyanations, see (a) M. S. Sigman,... 

For a recent overview on asymmetric cyanation of ketimines, using various Lewis and Bmnsted adds, see Spino, C., Angew. Chem., Int. Ed. 2004, 43, 1764. 

Asymmetric cyanation of aldehydes is important in organic synthesis. Mukaiyama and Minowa have developed a new chiral Lewis acid catalyst which is readily prepared from l,l -dimethylstannocene, triflic acid, and (+)-cinchonine [49]. In the presence of this Lewis acid reaction of TMSCN with aldehydes proceed smoothly at -78 °C in dichloromethane to give the corresponding cyanohydrin trimethylsilyl ether in high yield with good to excellent ee. In this reaction the products are isolated as trimethylsilyl ethers and the reaction proceeds smoothly in the presence of 30 mol % tin(II) Lewis acid (Eq. 31). The catalyst, Sn(II) monoalkoxymonotriflate, is assumed to be regenerated from the initially produced Sn(II) alkoxide and trimethylsilyl triflate. 

The catalytic asymmetric cyanation of imines-the Strecker reaction-represents one of the most direct and viable methods for the asymmetric synthesis of a-amino... 

Asymmetric Cyanation Catalyzed by Chiral Lewis Acids. 7... 

Accordingly, the design of the catalyst for asymmetric cyanation has mainly been performed using natural alkaloids, amino acid derived compounds with a basic moiety in the substituent, and Lewis acidic organometaUics modified with optically active compounds [11]. 

On the other hand, only few studies have been successful in the asymmetric cyanation of imines compared with that of carbonyl compounds since imines,in general, themselves promote the cyanation reaction without a catalyst. 

The reaction of benzaldehyde with hydrogen cyanide in the presence of 2 mol % of the catalyst in toluene at -20 °C for 8 h furnished the corresponding (i )-cyanohydrin in 97% yield and an enantioselectivity of 97%. The asymmetric cyanation of various aromatic and heteroaromatic aldehydes similarly proceeded to give the optically active cyanohydrins, although aromatic aldehydes with electron withdrawing groups such as NO2 and CN and aliphatic aldehydes... 

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]. 

Asymmetric Cyanation of C=0 Bonds by Metal-Catalyzed Reactions... 

Cyano(trimehyl)silane (TMSCN) serves as a cyanating agent for carbonyl groups in the presence of a catalytic or stoichiometric amount of a Lewis acid such as boron trifluoride, titanium(IV) chloride, tin(IV) chloride, etc. Thereby, a wide variety of chiral ligands was designed and used for asymmetric cyanation reactions. Among them, titanium complexes have mostly been employed as the catalysts. 

Catalytic asymmetric cyanation using 20 mol % of the complex of Ti(Oz-Pr)4 with diisoporpyl tartrate (10 Fig. 1) was reported by Oguni [42,43]. The mixture of Ti(Oi-Pr)4 and 10 (Fig. l)did not exhibit high enantioselectivity. Moreover, the selectivity and the reactivity were still low when the formed isopropyl alcho-hol was removed under reduced pressure using the freeze-dry method. High reactivity and an enantioselectivity of up to 90% were observed when the isopropyl alcohol was again added to the freeze-dried titanium complex. 

Cyanadons. Aluminum complexes of BINOLs (1) that are armed at C-3 and C-3 with diarylphosphine oxide groups possess both Lewis acid and base centers. Asymmetric cyanation of aldehydes and mines with MeaSiCN, and of quinolines and isoquinolines in a manner analogous to the Reissert reaction is successful (ee 70-90%). The asymmetric Strecker synthesis is applicable to conjugated aldimines and the higher reactivity of Me SiCN than HCN in the presence of 10 mol% of PhOH enables its use in catalytic amount while supplying stoichiometric HCN as the cyanide source. 

---