Reductive Formylation Research Articles

Effective Formylation of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by Chelating bis(tzNHC) Rhodium Complexes.

The reductive formylation of amines using CO2 and hydrosilanes is an attractive method for incorporating CO2 into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N-heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO2 and Ph2SiH2. A rhodium-based bis(tzNHC) complex (tz=1,2,3-triazol-5-ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.

Pd/C-Catalyzed Reductive Formylation of Indoles and Quinolines Using Formic Acid

A two-step, one-pot domino reaction methodology was developed to synthesize a variety of N-formylindolines and N-formyltetrahydroquinolines from the corresponding indoles and quinolines. In the first step, the heterocyclic compounds are reduced to the corresponding dihydro or tetrahydro products by a Pd/C-catalyzed transfer hydrogenation using formic acid as a hydrogen donor. In the second step, nitrogen is formylated by formic acid to afford the final products in very good isolated yields.

ChemInform Abstract: Reductive Formylation of Isoquinoline Derivatives with Formamide and Synthesis of 2‐Formyltetrahydroisoquinolines.

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Reductive Formylation of Isoquinoline Derivatives with Formamide and Synthesis of 2-Formyltetrahydroisoquinolines

Reductive formylation of isoquinoline derivatives as 3,4-dihydroiso-quinolines 1, enamines and enamides of tetrahydroisoquinoline 2 and the reaction of 2-(2-acylphenyl)ethylamides 3 with formamide afforded the corresponding N-formyltetrahydroisoquinolines 4 and N-acyltetrahydroisoquinolines 5.

Synthesis and anti‐tetrabenazine activity of c‐3 analogues of dimethyl‐2‐phenylmorpholines

AbstractA series of analogues of 2‐phenylmorpholines with alkyl substituents at the C‐3 position were synthesized for anti‐tetrabenazine (anti‐TBZ) testing in mice. The target compounds were prepared by reaction of (2‐bromoalkyl) phenyl ketones 21a‐h with the appropriate aminoalcohol 20a‐b to form morpholinols 22a‐h. Hydride reduction of the morpholinols gave aminodiols 23a‐h which were cyclized to morpholines 6, 8, 10–12, 14–16, 18 and 19 by acid catalaysis. Compounds 7, 9, 13 and 17 were prepared by reductive formylation. The smaller straight chain substituents of 6, 8, 12 and 15, and the beta branching of the iso‐butyl group of 16 were well tolerated; anti‐tetrabenazine ED50′s were comparable to compounds 2–5. The α‐branched, N‐methylated, and side chain aryl derivatives were less active.

Synthesis of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid, a potent broad spectrum β-lactamase inhibitor, from 6-aminopenicillanic acid

(5R)-(Z)-6-(1-Methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34(BRL 42715) has been prepared from 6-aminopenicillanic acid 4(6-APA) by a short, stereoselective and efficient route via the novel intermediate, p-methoxybenzyl (5R, 6S)-6-bromopenem-3-carboxylate 17.Elaboration of 6-APA 4 to the azetidinone disulfide 10 by established methodology, followed by reductive formylation provided the crystalline C-4 formylthio-azetidinone derivative 29. Cyclization of the oxalimide 28, obtained by ozonolysis of the formylthio derivative 29, to the crystalline 6α-bromopenem ester 17 was effected by way of the phosphite-mediated carbonyl–carbonyl coupling reaction.Sequential treatment of bromopenem 17 with lithium diphenylamide, 1-methyl-1,2,3-triazole-4-carbaldehyde, and acetic anhydride gave a diastereoisomeric mixture of acylated bromohydrins 32; reductive elimination of this mixture afforded a separable mixture of (Z)- and (E)-triazolylmethylene penem esters, 33 and 35 respectively. Lewis acid-mediated deprotection of ester 33 provided (5R)(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34(BRL 42715) as a crystalline sodium salt monohydrate.The 6-heterocyclylmethylene penems, represented by BRL 42715, are potent inhibitors of bacterial β-lactamases and their combination with an appropriate penicillin or cephalosporin results in good synergistic activity against a broad range of β-lactamase-producing bacteria.

ChemInform Abstract: Reductive Formylation of Oximes. An Approach to the Synthesis of Vinyl Isonitriles.

Abstract Reduction of ketoximes using anhydrous titanium-(III)-acetate in the presence of mixed formic-acetic anhydride yields N-formyl enamines which may be dehydrated to vinyl isonitriles.

Reductive formylation of oximes; an approach to the synthesis of vinyl isonitriles

Reduction of ketoximes using anhydrous titanium-(III)-acetate in the presence of mixed formic-acetic anhydride yields N-formyl enamines which may be dehydrated to vinyl isonitriles.

Reductive formylation of aromatic halides under low carbon monoxide pressure catalyzed by transition-metal compounds

Formylation en particulier de l'iodo- et bromo-benzene avec le monoxyde de carbone en presence de polysiloxanes et de complexes de Pd dans acetonitrile-HMPT, acetonitrile-DMSO

Reductive formylation of N,N-dimethyl-p-nitrosoaniline by glyoxylic acid. Evidence for a hydroxamic acid intermediate

Reductive formylation of N,N-dimethyl-p-nitrosoaniline by glyoxylic acid. Evidence for a hydroxamic acid intermediate

Cinnolines. Part XIV. Reductive Formylation of Cinnolines to 1-Formamidoindoles

The reductive formylation of cinnolines by heating with formic acid and formamide gives the corresponding 1-formamidoindole; cinnoline-4-carboxylic acid is decarboxylated during the reaction.

The reductive formylation of some quinoxaline derivatives

Reduction of quinoxaline and its 2-methyl derivative by formic acid in formamide yields a mixture of the corresponding NN′-diformyl-1,2,3,4-tetrahydro-compound and 2,2′-biquinoxalinyl. 2-Hydroxyquinoxalines are converted into 4-formyl-1,2,3,4-tetrahydro-2-oxoquinoxalines. Condensation products formed from acetone and some nitroquinoxalines are described.