Otto Meth-Cohn

Regioselective electrophilic formylation—3-substituted thiophenes as a case study

Abstract A variety of methods for regioselective formylation have been examined and exemplified with 3-methylthiophene. Optimal yields and regioselectivity for 2-formylation were obtained with N -formylpyrrolidine (11:1) although up to a 46:1 ratio could be obtained with MeOCHCl 2 :TiCl 4 , albeit in lower yield. Optimal 5-formylation (1:1.5) was obtained when using N -formylindoline:(COCl) 2 .

Microbial desymmetrization of 3-arylglutaronitriles, an unusual enhancement of enantioselectivity in the presence of additives

In the presence of an organic additive such as acetone or β-cyclodextrin or in a biphasic system of hexane and aqueous phosphate buffer, microbial desymmetrization of 3-arylglutaronitriles catalyzed by Rhodococcus sp. AJ270 cells proceeded regiospecifically and enantioselectively to produce S-(+)-3-aryl-4-cyanobutyric acids in high enantiomeric excess. Convenient chemoenzymatic syntheses of optically active R-(−)-4-amino-3-phenylbutyric acid and 4R-(−)-4-phenyltetrahydropyran-2-one are described.

A concise synthesis of homochiral sedamines and related alkaloids. A new reductive application of Jacobsen's catalyst

Abstract Two methods for the generation of both enantiomers of sedamine [1-methyl-2-(2-phenyl-2-hydroxy-1-ethyl)piperidine] in high optical purity have been elaborated. The first utilises the lipase-mediated kinetic resolution of racemic acetates and the second involves the NaBH 4 mediated reduction of ketones catalysed by Jacobsens catalyst. Some related applications of these reactions are also disclosed.

The reverse vilsmeier approach to the synthesis of quinolines, quinolinium salts and quinolones

Abstract N-Methylformanilide(MFA) reacts with various electron-rich alkenes in POCl3 solution to give N-methylquinolinium salts generally in good yield The alkenes can be vinyl acetate, an aldehyde or ketone enamine (preferably the morpholine enamine), a methyl aryl ketone (reacting as its enol) or it may be generated from an alkanoamide bearing α-protons (which produces an α-chloroenamine in situ). The reaction is effective for a variety of other alkyl-, aryl- and benzylformanilides as well as ring substituted anilides though electron-withdrawing groups tend to inhibit cyclisation. The mechanism of the cychsation has been elucidated and shown to involve an electrocyclic π6s process The reactions of MFA with amides in POCl3 gives 4-quinolones on alkaline workup.

A powerful new nitrile hydratase for organic synthesis — aromatic and heteroaromatic nitrile hydrolyses — a rationalisation

Abstract A powerful new nitrile hydratase organism, Rhodococcus rhodocrous AJ270 has been isolated that efficiently hydrolyses all kinds of nitriles to amides and/or acids. This paper shows that aromatic and heterocyclic nitriles are readily hydrolysed to acids but, that those bearing an adjacent-substituent (which may be an ortho substituent or an adjacent heteroatom in the ring) give amides in good yield but only slowly proceed to acids.

The synthesis and ligand properties of N,N′-Polymethylene - bridged imidazole-2-thiones and benzimidazole-2-thiones

Abstract A series of N,N′-polymethylene-bridged imidazole- and benzimidazole- 2-thiones have been made with the bridge containing 1 to 6 methylenes, the former by alkylation of N-methyl-imidazole by α,ω-dibromoalkanes followed by thiation with sulphur and the latter from the previously described bridged benzimidazolones by treatment firstly with phosphoryl chloride followed by thiourea. The bridged benzimidazolethiones formed complexes with mercury, palladium and copper salts but not with iron, cobalt, nickel, zinc, platinum, cadmium, silver or thallium. The imidazolethiones complexed with iron, cobalt, nickel, copper, zinc, tin, cadmium, palladium, platinum and silver salts.

A rapid, simple route to homochiral α,β-epoxyketones

Abstract Substituted E- or Z-acrylylamides derived from a homochiral amine such as (R,R)-2,5-dimethylpyrrolidine or (S,S)-bis(2-phenylethyl)amine are readily epoxidised with complete stereocontrol with t-BuO 2 Li to give two readily separated, enantiomerically pure diastereomeric epoxides. The easily separated epoxides are efficiently converted into α,β-epoxyketones by the action of organolithiums with 92→99% ee.

Synthetic applications of umpoled vilsmeier reagents — A new simple one-pot route to isatins from formanilides

Abstract When N -substituted formanilides are treated briefly and sequentially with oxalyl chloride, Hunigs base, and bromine, isatins are rapidly formed, many in good yields. The reaction involves deprotonation of the Vilsmeier reagent, dimerisation of the carbene thus formed and electrophilic cyclisation of the dimer by bromonium ion action followed by aqueous hydrolysis.

The photochemistry of α-Azidocinnamates - a reinvestigation

Abstract α-Azidocinnamates have been reported elsewhere to yield one diastereomer of a trimer in a stepwise and efficient manner by photolysis using quartz equipment. 1 We find that use of pyrex filters or ketone sensitisation instead of quartz leads to high yields of the presumed intermediate diastereomeric pair of aziridinoimidazoline dimers, as does brief irradiation in quartz. These dimers have been characterised by spectral and crystallographic methods, and shown to oxidise with DDQ to give imidazoledicarboxylic esters, while the action of base on both dimer diastereomers leads to one rearranged dimer, a 1,2-dihydropyrimidine. Surprisingly, only a mixture of both diastereomeric dimers gives the trimer on further photolysis.

Rationalisation of the regioselective hydrolysis of aliphatic dinitriles with Rhodococcus rhodochrous AJ270

Aliphatic dinitriles undergo regioselective hydrolysis with the title organism to give monoacids with up to four methylenes between the nitrile functions (optimally 2–3) or when either an oxygen is placed β, γ or δ to the nitrile (δ-placement being optimal) or β or γ (optimally γ) but not δ sulfur substituents are present; nitrogen substituents appear to behave as for oxygen but suffer a steric limitation of the size of the nitrogen substituent.