Joyram Guin

Biomimetic carbene-catalyzed oxidations of aldehydes using TEMPO.

Pyruvate ferredoxin oxidoreductase (PFOR), which catalyzes the oxidative decarboxylation of pyruvate to form acetyl-CoA and CO2, belongs to the family of 2-keto acid oxidoreductases. This CoA-dependent enzyme uses thiamine pyrophosphate (TPP) as an additional cofactor. The anaerobic decarboxylation is a reversible process, and the two electrons obtained during one turnover are transferred to ferredoxine via [Fe4S4] clusters. [1] The initial steps of the oxidative decarboxylation resemble those of the aerobic TPP-dependent 2-oxoacid dehydrogenases. Pyruvate reacts with A to form B after proton transfer, and B subsequently undergoes CO2 elimination to generate C (Scheme 1). Electron transfer to a [Fe4S4] cluster leads to radical cation D. Although intensive studies (X-ray and EPR) have been conducted on D, the structure of the radical cation is still under debate. Renewed electron transfer in the presence of CoASH eventually leads to CoASAc. In aerobic organisms lacking the [Fe4S4] clusters, C reacts with the dithiolane ring of a lipoyl group in a formal twoelectron transfer to an acetyl lipoamide thioester intermediate, which is further transformed in the presence of CoASH using another enzyme to CoASAc. The liberated dithiol is eventually reoxidized to the cyclic disulfide by a FADdependent dihydrolipoyl dehydrogenase. It is known in synthesis that reaction of aldehydes with thiazolium carbenes leads to intermediates of type C which react as “umpoled” nucleophiles with aromatic aldehydes (benzoin condensation) or with electron-poor olefins (Stetter reaction). Recently, N-heterocyclic carbene (NHC) catalyzed transformations have gained increasing attention. However, these investigations have focused on ionic processes. Guided by PFOR we planned to oxidize enamines of type C by organic single-electron transfer (SET) oxidants. The process would represent a biomimetic transition-metalfree organocatalytic oxidation of an aldehyde. As the oxidant we used 2,2,6,6-tetramethylpiperidine N-oxyl radical (TEMPO), which has been used successfully by our group in transition-metal-mediated reactions and in various radical processes. Hence, the oxidizing [Fe4S4] clusters in PFOR can be replaced by two oxidizing TEMPO units [Eq. (1)].

Catalytic Asymmetric Protonation of Silyl Ketene Imines

An efficient catalytic and highly enantioselective protonation of silyl ketene imines is described. The reaction is catalyzed by the chiral phosphoric acids TRIP or STRIP in the presence of a stoichiometric amount of methanol as the proton source and silyl acceptor. A variety of substituted racemic silyl ketene imines have been transformed into highly enantioenriched nitriles.

Synthesis, Resolution, and Stabilities of a Cationic Chromenoxanthene [4]helicene

1,13-Dimethoxychromenoxanthenium, a key intermediate in the synthesis of the classical trioxatriangulenium cation, was isolated and characterized for the first time. This [4]helicene was resolved through a CSP-HPLC procedure, with chemical and configurational stabilities being determined and compared.

Radical‐Transfer Hydroamination of Olefins with N‐Aminated Dihydropyridines

An efficient synthesis of N-phthalimidyl, benzamidyl, acetamidyl, carbamoyl, and ureayl derivatives of dihydropyridines and the application of these reagents as precursors for N-centered radicals are presented. These aminated dihydropyridines could be used in radical-transfer hydroamination reactions of various electron-rich as well as nonactivated olefins in the presence of thiols as polarity-reversal catalysts. These reactions worked without the aid of any transition metal. Steric and electronic effects exerted by the N-substituents of the N-centered radicals are discussed. In contrast to most metal-catalyzed processes, the radical hydroamination delivered the opposite regioisomer with excellent anti-Markovnikov selectivity. Hydroamination products were obtained as protected amines that are readily isolated.

Highly selective additions of hydride and organolithium nucleophiles to helical carbenium ions

Unsymmetrical cationic [4]helicenes react with hydride or organolithium reagents and the two diastereotopic faces can be discriminated with high efficiency (dr up to and higher than 49 : 1)

Asymmetric counteranion-directed Lewis acid organocatalysis for the scalable cyanosilylation of aldehydes

Due to the high versatility of chiral cyanohydrins, the catalytic asymmetric cyanation reaction of carbonyl compounds has attracted widespread interest. However, efficient protocols that function at a preparative scale with low catalyst loading are still rare. Here, asymmetric counteranion-directed Lewis acid organocatalysis proves to be remarkably successful in addressing this problem and enabled a molar-scale cyanosilylation in quantitative yield and with excellent enantioselectivity. Also, the catalyst loading could be lowered to a part-per-million level (50 ppm: 0.005 mol%). A readily accessible chiral disulfonimide was used, which in combination with trimethylsilyl cyanide, turned into the active silylium Lewis acid organocatalyst. The nature of a peculiar phenomenon referred to as a “dormant period”, which is mainly induced by water, was systematically investigated by means of in situ Fourier transform infrared analysis.