Amines strecker-type reaction

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

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]. 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Several examples of the Strecker-type reaction were tested. For all the compounds investigated, including aromatic, aliphatic, heterocyclic, and aj3-unsaturated aldehydes, the reactions proceeded smoothly to afford the corresponding a-amino nitriles in high yield. The adducts, a-(A-benzhydryl)amino nitriles, were readily converted to a-amino acids [78], and Strecker-type reactions using other amines such as aniline and benzylamine also proceeded smoothly to afford the corresponding adducts in high yields. 

Aromatic and aliphatic aldehydes in the presence of dialkylamines and an equivalent of acid such as hydrochloric, perchloric or p-toluenesulfonic acid give iminium salts, which add cyanide ion to form a-(dialkylamino)nitriles. An alternative preparation involves the reaction of the aldehyde with dialkylamines in the presence of acetone-cyanohydrin, a-(A, -dialkylamino)isobutyronitiiles, diethyl phosphorocyanidate or TMS-CN. Another route to a-aminonitrile starts with an aldehyde, the salt of an amine and KCN in organic solvents under solid-liquid two-phase conditions by combined use of alumina and ultrasound. Chiral a-aminonitriles were prepared by Strecker-type reactions, cyano-silylation of Schiffs bases, amination of a-siloxynitriles or from an A -cyanomethyl-l,3-oxazolidine synthon. Reaction of tertiary amines with CIO2 in the presence of 5.1 mol equiv. of aqueous NaCN as an external nucleophile affords a-aminonitrile. °... 

Thus, Strecker-type reactions of aldehydes, amines, and Bu3SnCN were successfully performed using Sc(OTf)3 as a catalyst. The reactions proceeded smoothly in both organic and aqueous solutions to afford a-amino nitriles in high yields. It is noted that the experimental procedure is very simple just mixing the three components and Sc(OTf)3 in an appropriate solvent at room temperature. Moreover, complete recovery of the tin materials in these reactions has been achieved. While many useful tin reagents have been... 

M. Ayaz, P. De Morales, and C. Hulme, A Carbonyl Compound as ElectrophUic Compound — With an Amine or Analogue as One Nucleophile Component — Third Component Cyanide (Strecker and Strecker-Type Reactions), In T.J.J. MiiUer, editor Multicomponent Reactions 1, Science of Synthesis, Georg Thieme Verlag Stuttgart (2014), p 99. 

Hao and colleagues disclosed a rapid total synthesis of ( )-tr onoliimine A via a Strecker/Houben-Hoesch sequence.The three-component Strecker-type reaction of 169, 170, and TMSCN was found to be effectively promoted by TMSOTf to furnish intermediate 171 this intermediate was unstable in basic or neutral environments and thus was treated directly with triflic acid at room temperature to effect the Houben-Hoesch cyclization and give ketone 172. Finally, the addition of hydrazine triggered deprotection of the amine and subsequent cyclization to furnish 173 (130L528). 

S. Kobayashi, T. Busujima, S. Nagayama, Chem. Commun. 1998, 981-982. Scandium triflate-catalyzed Strecker-type reactions of aldehydes, amines and tributyltin cyanide in both organic and aqueous solutions. Achievement of complete recovery of the tin compounds toward environmentally-friendly chemical processes. 

Kobayashi et al. reported that Strecker-type reaction of aldehydes, amines, and TMSCN proceeded efficiently with Yb(OTf)3 as catalyst [30]. Both aliphatic and aromatic aldehydes afforded the corresponding a-aminonitrile in high yield... 

Rueping et al. also developed separate conditions for the addition of phosphates, cyanide, and acetylides. Cyanations (or Strecker-type reactions) of THIQ derivatives were achieved using Ir(tbppy)2(bpy)PF6 (tbppy=2-(4-rert-bu1yl-phenyl)-pyridine 4) in acetonitrile and tertiary benzylic amines with potassium cyanide, in which the addition of acetic acid was crucial for HCN liberation and solubility. Product yields range from 81-97% (Scheme 10.7). In addition to THIQ derivatives, substituted anilines also underwent coupling, with allq l C-H bonds oxidized in preference to benzylic C-H bonds. 

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

Amines via condensations. Tryptophan derivatives are obtained by reaction of indoles with A-substituted aziridinecarboxylic esters at 0° or room temperature. Stoichiometric amount of Sc(OTf)3 is required. By SclOTfjj catalysis the Strecker-type synthesis from aldehydes, amines, and BujSnCN can be carried out either in organic solvents or in water. Pictet-Spengler reaction is directly accomplished using acetals. ... 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

Each elementary step is reversible. At fist glance, this type of reaction should afford a complex reaction mixture of product, all possible intermediates, and starting materials. However, if the desired adduct is thermodynamically more stable than any other intermediates, the reaction can still be high yielding and become synthetically useful. The Strecker reaction is a typical example. Although the condensation of an aldehyde, an amine leading to iminium intermediate and subsequent nucleophilic addition of cyanide are in principle reversible under aqueous acidic conditions. The a-aminonitrile can be obtained in high yield under appropriate conditions. 

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