Dibutyltin Chloride Hydride Complex as a Novel Reductant for Chemoselective Reductive Amination

Abstract

Imine-selective reducing agent Bu 2 SnClH-HMPA (I) performed effective reductive amination of carbonyl compounds. Various functionalized amines could be prepared in a one-pot procedure. Noteworthy is that highly chemoselective reactions were achieved with the co-existence of other functionalities such as halogen, carbon-carbon double bond and hydroxyl groups.Reductive amination of aldehydes is one of the most convenient routes to various secondary amines, in which three components of carbonyls, amines and reductants are treated in one portion. 1 By this procedure, a wide range of functionalized amines can be prepared because intermediate imines, in particular unstable ones, do not have to be isolated. The choice of the reductant is very critical since the undesirable reduction of the carbonyls must be depressed to form intermediate imines. Sodium cyanoborohydride (NaBH 3 CN) has been used because of its wide applicability. 2 However, there are some drawbacks because of the requirement of excess amounts of amines and inapplication to weak bases such as aromatic amines. To solve these problems, modified borohydrides have been developed. 3 However, alternative metal hydride reagents have scarcely been focused so far. We have provided a set of organotin hydrides by the introduction of a halogen substituent or a ligand on the tin atom to achieve highly chemoselective reductions of multifunctionalized substrates. 4 The fivecoordinated tin hydride, Bu 2 SnClH-HMPA (I), 5 easily formed in situ from Bu 2 SnClH 6 and HMPA, has been revealed to reduce imines even in the presence of carbonyls. 7 This high imine-selectivity indicates that the reagent I would be a good candidate for the reductive amination. We present here the first use of tin hydrides for reductive amination of aldehydes and ketones under mild and neutral conditions (Scheme 1). The characteristic features are as follows. 1) Effective reactions proceeded in particular for the case using aromatic amines as starting substrates. 2) Stoichiometric amounts of substrates and tin reductant were adequate. 3) Co-existence of other functionalities was allowed in the starting carbonyls 1 and amines 2. Scheme 1Table 1 summarizes the reductive aminations of various carbonyl compounds by using Bu 2 SnClH-HMPA (I). The three reagents, the tin hydride I, carbonyl compound 1 and aniline 2a were successively added to THF solvent. Initially, we examined the reductive aminations of benzaldehyde 1a. The reaction with aniline 2a proceeded smoothly to give the corresponding secondary amines, 3aa in good yield (entry 1). 8 Benzyl alcohol derived from the reduction of starting material 1a was not produced under these conditions. Instead of 2a, the use of more weakly basic p-chloroaniline 2b also gave the corresponding secondary amine 3ab in good yield (entry 2). Next, other aromatic aldehydes were examined. In entry 3, the reducing system (I) did not affect the bromine functionality at all, which is generally reducible by trialkyltin hydrides. 9 In the reaction of 1c, the hydroxy grou...

Direct Reductive Amination of Aldehydes and Ketones Using Phenylsilane: Catalysis by Dibutyltin Dichloride

“…Direct reductive aminations are known to be promoted by Bu 2 SnClH under conditions similar to those we report here (ref ). Although our results are not inconsistent with the catalytic intermediacy of such a species, other possibilities, including simple acid catalysis either by Bu 2 SnCl 2 itself or a hydrolysis product, cannot be ruled out.…”

“…The direct reductive amination of aldehydes and ketones is used extensively to prepare primary, secondary, and tertiary amines (Scheme ). , This reaction offers compelling advantages over other amine syntheses, including brevity, wide commercial availability of substrates, generally mild reaction conditions, and in some cases exceptionally high functional group tolerance. Several reagents which effect direct reductive amination have been recently developed, including the following: NaBH(OAc) 3 ;1a ZnCl 2 −NaBH 4 ; NiCl 2 −NaBH 4 ; Ti(O i Pr) 4 −polymethylhydrosiloxane; Ti(O i Pr) 4 −NaBH 4 ; Bu 3 SnH; Bu 2 SnClH and Bu 2 SnIH; decaborane; silica gel−ZnBH 4 ; Et 3 SiH−trifluoroacetic acid; pyridine−BH 3 . Reductive N -alkylation of amides with carbonyl compounds using Et 3 SiH−trifluoroacetic acid has also been described …”

Chemoselective Reductive Amination of Aldehydes and Ketones by Dibutylchlorotin Hydride-HMPA Complex

“…In order to explore this high imine reduction selectivity of Bu 2 SnClH-HMPA, we investigated the details of reductive amination of various aldehydes and ketones to give a variety of secondary and tertiary amines under mild and neutral conditions (Scheme 2). 10 The characteristic features of the reduction with Bu 2 SnClH-HMPA are as follows: (1) weakly basic aromatic amines 2 are effectively employed;…”

PS-Pd–NHC: an efficient and heterogeneous recyclable catalyst for direct reductive amination of carbonyl compounds with primary/secondary amines in aqueous medium

“…1,2 Direct reductive amination (DRA) of carbonyl compounds with amines is one of the most useful methods for one step synthesis of secondary or tertiary amines and related functional compounds. 3,4 For this transformation various boron-based reagents have been developed including borane-pyridine, 5 sodium borohydride-magnesium perchlorate, 6 ZnBH 4 -ZnCl 2 , 7 NaBH(OAc) 3 , 8 silica gel-ZnBH 4 , 9 dibutyl tin chloride hydride, 10 NaBH 3 CN 11 and InCl 3 /Et 3 SiH. 12 However, these systems require the use of a stoichiometric amount of hydride source, excess amine and acidic reaction conditions.…”