Amines chemoselective reduction

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

The hydrosilylation of terminal alkynes disclosed by Trost can be applied to internal alkynes as well. i Remarkably, the (Z)-isomer is generated in this process, resulting from trans addition during hydrosilylation. The protodesilylation of these sily-lated products in the presence of copper(I) iodide and tetrabuty-lammonium fluoride (TBAF) or silver(I) fluoride (eq 15) leads to internal fraws-olefins. This two-step method is a useful synthetic transformation to access ( j-alkenes from internal alkynes. In contrast, the chemoselective reduction of alkynes to the corresponding ( -alkenes is conventionally accomplished readily with Lindlar s catalyst. The complementary process to afford ( )-olefins has proven much more difficult. Methods involving metal hydrides, dissolving metal reductions, low-valent chromium salts provide the desired chemical conversion, albeit with certain limitations. For example, functional substitution at the propargylic position (alcohols, amines, and carbonyl units) is often necessary to achieve selectivity in these transformations. Conversely, the hydrosilylation/protodesilyla-tion protocol is a mild method for the reduction of alkynes to ( )-alkenes. 

Two alternative routes to (+)-swainsonine (ent-37S) developed by Chen and Tsai, Hke that used in their synthesis of lentiginosine (c Scheme 47 Section 3.3.2), created the bond to C-8a by means of free radical cycUzations onto an acylsilane. The first approach entailed the creation of the C-l/C-8a bond (Scheme 86). Amide formation between the amine 638 and the acid chloride prepared in situ from the chiral lactone-acid 639 yielded (—)-640, which was cyclized with base to the imide (—)-641 in 91% yield. Chemoselective reduction of the C-2 carbonyl group, acid-catalyzed reaction with thiophenol, and protection of the hydroxyl substituent as the benzoate gave 642 as a mixture of isomers. After hydrolysis of the dithiane to the acylsilane 643 with iodobenzene bis(trifluoroacetate), treatment with tri-butyltin hydride and l,lCazobis(cyclohexane-l-carbonitrile) (ACCN) as radical initiator produced the indohzidin-5-one 644 in 86% yield as a... 

Chemoselective reduction with NaBH4 followed by tert-butyldiphenylsilyl (TBDPS) protection provided the protected diol 106 in ca. 40% yield over four steps. Then, Parkins hydration of the nitrile moiety followed by reduction of the azide afforded the amido Boc-amine 107, which finally underwent Hoffman rearrangement to yield the key intermediate 108 as a single diastereomer in ca. 15% overall yield (nine steps) with 92% ee. 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Electrocatalytic hydrogenation has the advantage of milder reaction conditions compared to catalytic hydrogenation. The development of various electrode materials (e.g., massive electrodes, powder cathodes, polymer film electrodes) and the optimization of reaction conditions have led to highly selective electrocatalytic hydrogenations. These are very suitable for the conversion of aliphatic and aromatic nitro compounds to amines and a, fi-unsaturated ketones to saturated ketones. The field is reviewed with 173 references in [158]. While the reduction of conjugated enones does not always proceed chemoselectively at a Hg cathode, the use of a carbon felt electrode coated with polyviologen/Pd particles provided saturated ketones exclusively (Fig. 34) [159]. 

A pH-dependent chemoselective catalytic reductive amination of a-keto acids, affording a-amino acids with HCOONH4 in water, was achieved using the complex 31 or its precursor 28 as the catalyst [51]. The formation rates of alanine and lactic acid from pyruvic acid exhibited a maximum value around pH 5 and pH 3, respectively, and therefore, alanine was obtained quite selectively (96%) with a small amount of lactic acid (4%) at pH 5 (Scheme 5.18). A variety of nonpolar, uncharged polar and charged polar amino acids were also synthesized in high yields. 

The Br0nsted acid catalyzed enantioselective reduction of several methyl-aryl ketimines affords the corresponding amines in good yields and enantioselectivities (Table 4.1). The mild reaction conditions and generally good chemoselectivity of this transfer hydrogenation render this transformation an attractive and metal-free approach to optically active amines. 

Rapid reduction of aromatic nitro compounds into amines has been described using sodium hypophosphite and FeSC>4-7H20. The reactions showed best results in terms of yields and purity, when the substrates were pre-absorbed on alumina and irradiated by microwaves under solvent-free conditions. The reaction is chemoselective and does not affect functional groups such as CN, OH, COOH, CONH2 or halogens. In addition, oximes were not reduced under the given reaction conditions, but were dehydrated to the corresponding nitriles instead (Scheme 4.32)57. 

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