Strecker metal-catalyzed

The addition of cyanide to imines, the Strecker reaction, constitutes an interesting strategy for the asymmetric synthesis of a-amino acid derivatives. Sigman and Jacobsen150 reported the first example of a metal-catalyzed enan-tioselective Strecker reaction using chiral salen Al(III) complexes 143 as the catalyst (see Scheme 2-59). 

Sigman and Jacobsen reported the first example of a metal-catalyzed enantioselective Strecker-type reaction using a chiral Alnl-salen complex (salen = N,N -bis(salicyhdene)-ethylenediamine dianion) [4]. A variety of N-allylimines 4 were evaluated in the reaction catalyzed by complex 5 to give products 6, which were isolated as trifluoroacetamides in good yields and moderate-to-excellent enantioselectivities (Scheme 3). Substituted arylimines 4 were the best substrates, while alkyl-substituted imines afforded products with considerably lower ee values. Jacobsen and co-workers also reported that non-metal Schiff base catalysts 8 and 9 proved to be effective in the Strecker reaction of imines 7 with hydrogen cyanide to afford trifluoroacetamides 10 after reaction with trifluoroacetic anhydride, since the free amines were not stable to chromatography (Scheme 4) [5]. 

During the study of ligands for metal-catalyzed asymmetric reactions, Sigman and Jacobsen identified urea 15a as an efficient catalyst for the Strecker reaction in 1998 (Figure 10.15, Equation 10.29) [58]. 

Strecker reaction catalyzed by (i-PrO)4Ti whereby tosylimines accept Me3SiCN enantio-selectively is achieved by modifying the environment surrounding the metal center by alkoxy group exchange with 3,3 -di(P-naphthyl)-2,2 -dihydroxybiphenyl, and further complexation with cinchonine. ... 

The first multicomponent reaction was the Strecker reaction reported in 1850 by Adolf Strecker [241aj. It is a three-component coupling between carbonyl derivatives, amines, and cyanide source, such as hydrogen cyanide, to provide a-aminonitriles which constitute potent starting materials to achieve important a-amino acids by simple hydrolysis. The mechanism of the Strecker reaction involves the initial formation of an imine from condensation of the amine component to the carbonyl component, after which addition of the cyanide component to this imine intermediate follows. Although the first enantioselective, metal-catalyzed Strecker... 

In 1998, Jacobsen reported an asymmetric metal-catalyzed Strecker reaction that employs aluminium salen complex 145 (Equation 20) [105], Interestingly, the salen(aluminum) complex 145 proved superior to a wide range of other salen(metal) complexes both in terms of conversion and of enantioselectivity. This constituted the first example of successful use of a main group salen(metal) catalyst for asymmetric synthesis. The N-allylated imine 144 was thus converted into the trifluoroacetyl derivative 146 in 91 % yield and 95 % ee. 

In screening a library of these molecules with a variety of metal ions, it was found that the ligand in the absence of added metal was more active than the metal complexes tested. Three libraries were synthesized where sequential changes were made in the structures contained in each library. Ultimately, ligand 64, with a thiourea linker, was found to catalyze the Strecker reaction between benzaldehyde and HCN in 91% ee (Scheme 8). This system also catalyzed the addition of HCN to aliphatic aldehydes with selectivities of > 80% ee. 

The bifunctional mechanism proposed for the Ti-catalyzed Strecker suggests that electrophiles other than amines can be induced to undergo catalytic asymmetric additions with cyanide. The details of the optimal conditions (exactly what ligand structure, metal salt, solvent, and any needed additives) would however have to be identified through screening of parallel libraries as mentioned above. In this fashion, we have been able to develop an Al-catalyzed asymmetric... 

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. 

Job A, Janeck CF, Bettray W, Peters R, Enders D (2002) Tetrahedron 58 2253 Josephsohn NS, Kuntz KW, Snapper ML, Hoveyda AH (2001) Mechanism of enantioselective Ti-catalyzed Strecker reaction peptide-based metal complexes as bifunctional catalysts. J Am Chem Soc 123 11594—11599 Juhl K, Gathergood N, Jprgensen KA (2001) Catalytic asymmetric direct Man-nich reactions of carbonyl compounds with alpha-imino esters. Angew Chem Int Ed Engl 40 2995-2997... 

Chemical oxidation reactions and Strecker degradation of amino acids may also result in aldehyde formation (16). These reactions are important for the formation of acetaldehyde in baked or heated Sherries. Chemical oxidation reactions catalyzed by metal ions (Cu, Fe, Mn, Mo) can result in aldehyde production in oak aged distillates (20). Such reactions may also result in the formation of oxidation products from fatty acids released during the secondary fermentation of sparkling wines (21). 

The assymetric Strecker reaction of diverse imines, including aldimines as well as ketoimines, with HCN or TMSCN provides a direct access to various unnatural and natural amino acids in high enantiomeric excesses, using soluble or resin-linked non-metal Schiff bases the corresponding chiral catalysts are obtained and optimized by parallel combinatorial library synthesis [93]. A rather general asymmetric Strecker-type synthesis of various imines and a, 9-unsaturated derivatives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-containing complexes [94]. When chiral (salen)Al(III) complexes are employed for the hydrocyanation of aromatic substituted imines, excellent yields and enatio-selectivities are obtained [94]. 

Josephsohn, N. S., Kuntz, K. W., Snapper, M. L., Hoveyda, A. H. Mechanism of Enantioselective Ti-Catalyzed Strecker Reaction Peptide-Based Metal Complexes as Bifunctional Catalysts. J. Am. Chem. Soc. 2001,123,11594-11599. 

Chiral amines have been transformed into chiral imines RCH=NG, which are usually in equilibrium with the tautomeric enamines. These enamines undergo asymmetric alkylations, and the best results are often obtained with ethers 1.58 or with valine derivatives 1.59 (R = i-Pr, R = tert-Bu) [169, 173,253] in the presence of bases. Enamines, lithioenamines and zinc enamines derived from imines are very potent Michael donors that often participate in highly stereoselective reactions [161, 162, 169, 173, 254, 257, 260, 262, 267], Chiral imines can suffer very selective addition reactions of organomagnesium reagents [139, 253, 254] and allyl-metals [154, 258]. They also suffer stereoselective Ti-catalyzed silylcyanation [268], Strecker reaction [266], and [2+2] or [4+2] cydoadditions [131, 256, 263], When the reaction produces an imine product, the chiral auxiliary is recovered after acidic hydrolysis. However, when an amine is obtained as the product, as is often the case from phenethylamine derivatives, the chiral residue is cleaved by hy-drogenolysis. In such cases, the chiral amine is not, strictly speaking, a chiral auxiliary. But these processes will be discussed anyway because of their importance in asymmetric synthesis. 

The alkali-metal-salt-catalyzed enantioselective Strecker reaction of ketimines (176) with TMSCN has been developed by employing chiral (5)-BNPNa (177) (BNP = 1,1 -binaphthyl- 2,2 -diylphosphate) and PBAP (/ -t-butyl-6>-adamantylphenol) (Scheme 48). The simplicity and facile availability of the catalyst and high enantioselectivities of the reaction made it potentially applicable in synthesis. 

The Strecker reaction is an efQdent method for the preparation of a-amino acids which was first reported by Adolf Strecker over 100 years ago [120]. Now, several methods for asymmetric cyanations catalyzed by metal-complexes or organocata-lysts have been developed [121-124],... 

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