Direct Alkylative Passerini Reaction of Aldehydes, Isocyanides, and Free Aliphatic Alcohols Catalyzed by Indium(III) Triflate

Abstract

In(OTf)(3) was found to be a useful Lewis acid catalyst for direct alkylative Passerini reaction of aldehydes, isocyanides, and free aliphatic alcohols. In the present reaction, aromatic and alpha,beta-unsaturated aldehydes performed as nice substrates to give the corresponding alpha-alkoxy amide products in good yield.

Carboxylic Acid Free Novel Isocyanide‐Based Reactions

“…Recently, in 2006, an O ‐arylative Passerini reaction using nitrophenol derivatives was developed by El Kaim, Grimaud and co‐workers . Taguchi reported the direct alkylative Passerini reaction of aldehydes, isocyanides and a free aliphatic alcohol catalyzed by In(III) . Acetals and ketals are also useful for the reaction of an isocyanide catalyzed by Lewis or Brønsted acids, affording α‐alkoxyimidates …”

“…[10] Taguchi reported the direct alkylative Passerini reaction of aldehydes, isocyanides and a free aliphatic alcohol catalyzed by In(III). [11] Acetals and ketals are also useful for the reaction of an isocyanide catalyzed by Lewis or Brønsted acids, affording α-alkoxyimidates. [12] As described above, the acyl group in a carboxylic acid consequently acts as an electrophile and the OH group works as a nucleophile to the nitrilium intermediate in the Passerini reaction.…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…1a). Several orthoesters were applied in various domains as dehydrating agents, [5][6][7][8][9][10][11][12][13][14][15][16][17][18] alkylating agents, [19][20][21][22][23][24] dialkoxymethylation agents, 25 esterication agents, 26 methoxy sources, 27 additives, [28][29][30] solvents, [31][32][33] and protecting groups. [34][35][36] This functional group is also necessary for some conversions such as the Johnson-Claisen rearrangement.…”

“…85 Tetrahydropyranyl acetals containing a phenyl diazoketone substituent (24) underwent Rh(II)-catalyzed C-H insertion through an unusual C-O bond generation to give spirocyclic orthoesters (25) (Scheme 6). 86 3,4,6-Tri-O-acetyl-1,2-O-(1-tocopheroxyethylidene)-a-D-glucopyranose (vitamin E sugar 1,2-orthoester) (33)(34)(35)(36) with exo-type stereoselectivity were synthesized through the reaction of sugar halides (26)(27)(28)(29) with various phenols, such as a-tocopherol (30), chroman-6-ol (31), and 2,6-dimethylphenol (32) by N,N-diisopropylethylamine (DIPEA) and tetrabutylammonium iodide (TBAI) or tetraethylammonium bromide (TEABr) in reuxing CH 2 Cl 2 for 4-24 h. The obtained peracetylated orthoesters (33)(34)(35)(36) were deprotected by utilizing aminolysis (NH 3 /MeOH) or by reduction in the presence of DIBAL-H (Scheme 7). 87 Palladium on carbon (Pd/C) catalyzed the straightforward methoxylation of the benzylic positions of cyclic acetals (37) by i-Pr 2 NEt in reuxing methanol under atmospheric oxygen as a green oxidant to obtain orthoesters (38) (Scheme 8).…”

Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles

“…The methodology utilizes the conversion of an alcohol to an aldehyde using catalytic TEMPO, CuCl 2 and NaNO 2 [ 5 ]. In the presence of In(III), Passerini-type reactions have been reported between free alcohols (isopropanol), aldehydes (unsaturated and aryl) and isocyanides such as t -butyl isocyanide [ 6 ]. Pioneering work by El Kaïm and Grimaud led to the discovery of what is now known as the Passerini–Smiles reaction.…”