Chemoselective Reductive Amination of Carbonyl Compounds for the Synthesis of Tertiary Amines Using SnCl₂·2H₂O/PMHS/MeOH

Abstract

Stannous chloride catalyzed chemoselective reductive amination of a variety of carbonyl compounds with aromatic amines has been developed for the synthesis of a diverse range of tertiary amines using inexpensive polymethylhydrosiloxane as reducing agent in methanol. The present method is also applicable for the synthesis of secondary amines including heterocyclic ones.

Ligand‐free Iron(II)‐Catalyzed N‐Alkylation of Hindered Secondary Arylamines with Non‐activated Secondary and Primary Alcohols via a Carbocationic Pathway

“…Interstingly, 5 mol% iron(II) bromide was found be more efficient catalyst as compared to other iron salts (Table 1, entry 4). Dry toluene gave an optimum yield of the product as compared to other solvents (Table 1, entries 10-16 and see SI, Table S4, entries [1][2][3][4][5][6][7][8][9][10][11][12]. The effect of solvent was also investigated for this transformation.…”

“…[2] The alkylation of amines with alcohols to produce higher amines is an attractive and ecofriendly alternative to conventional methods, such as Buchwald-Hartwig amination, [3] reductive amination of carbonyl compounds, [4] hydroamination of alkynes/ alkenes [5] and CÀH nitrogen insertion. [2] The alkylation of amines with alcohols to produce higher amines is an attractive and ecofriendly alternative to conventional methods, such as Buchwald-Hartwig amination, [3] reductive amination of carbonyl compounds, [4] hydroamination of alkynes/ alkenes [5] and CÀH nitrogen insertion.…”

“…However, the major disadvantages of these protocols involved prolonged reaction time, high catalyst loading, ligand and elevated temperature for the N ‐ alkylation of secondary amine. Nevertheless, N‐alkylation of secondary arylamines with secondary benzyl alcohols is still a challenge due to the following reasons: (a) the larger size of secondary arylamines; they are generally considered more difficult coupling partners than primary anilines for N‐arylation reactions,, (b) as an alkylating agent, secondary alcohols are less reactive substrates as compared to primary alcohols in borrowing hydrogen transfer strategy because of the difficulty in its in situ dehydrogenation to the corresponding ketones,, (c) the hydrogenation of the iminium or enamine intermediate is also challenging (Scheme b) ,,…”

Tin‐Catalyzed Selective Reductive Hydroamination of Alkynes for the Synthesis of Tertiary Amines

“…The challenges associated with the non‐reactivity of secondary arylamines towards reductive hydroamination can be ascribed to their higher nucleophilicity that makes them strongly coordinated with metal salt, and the electrostatic repulsion between the more electron rich secondary arylamines and π‐electrons of alkyne. We recently reported a catalytic method for the synthesis of tertiary amines featuring tin‐catalyzed reductive amination of carbonyl compounds with secondary arylamines 3c. During this work, a unique compatibility of tin salts with secondary arylamines was observed.…”

Computational investigation of the control of the thermodynamics and microkinetics of the reductive amination reaction by solvent coordination and a co-catalyst

“…Several metal-based catalyst systems (such as Co 3 O 4 /H 2 and SnCl 2 /reducing agent) are mentioned in the literature as suitable candidates for this process. 11,18,19 There are also several successful experimental and computational reports on the functionalization of several amines via intra-and intermolecular cyclization reactions in a redox neutral way. [20][21][22] In addition, they give some evidence for the formation of ylide intermediates which suggests that the reaction can also proceed via an alternative route and would not necessarily involve the formation of iminium ions.…”