Alkyl pyrazines—other than being extracted from various natural sources such as coffee beans, cocoa beans, and vegetables—can be synthesized by chemical methods or by certain microorganisms. The importance of pyrazines for the food industry is expected to grow in the upcoming years due to the higher demand for convenience products. The roasty, nutty, and earthy smell is reminiscent of coffee and cocoa, depending on substitution and concentration of pyrazines. The growing awareness of people about the ingredients and the origin of their daily food has strongly influenced the market with labels like “organic” and “natural.” Many flavor ingredients prepared by biotechnological methods have conquered the market recently and are destined to replace the ineffective (0.01% pyrazine kg−1 biomass) extraction from plants or animal sources. This review focuses on the achievements and challenges in pyrazine synthesis. The major part deals with an overview of methods such as the extraction of natural products, the chemical and biocatalytic synthesis, and fermentation by microorganisms. The different types of production are decisive for the declaration and value of the final product and span from 200–3500 US$ kg−1 for the synthetically produced or the naturally extracted 2,5‐dimethylpyrazine, respectively.

Enzymatic methods for the oxidation of alcohols are critically reviewed. Dehydrogenases and oxidases are the most prominent biocatalysts, enabling the selective oxidation of primary alcohols into aldehydes or acids. In the case of secondary alcohols, region and/or enantioselective oxidation is possible. In this contribution, we outline the current state-of-the-art and discuss current limitations and promising solutions.

In recent years, interest in b-amino acids has continued to grow, being driven by their successful application in peptidomimetics and as valuable building blocks.[1] Therefore, development of new enantioselective approaches to b-amino acids and their derivatives remains in the focus of the fine chemicals industry, in spite of the existence of numerous methodologies, [2,3] . Readily available b-ketoesters 1 or related b-ketonitriles 2 can serve as convenient precursors of bamino acids, into which they can be converted, for example, by asymmetric reduction of the corresponding enamines 3 and 4 (Scheme 1). Catalytic hydrogenation, a preferred methodology in industry, generally requires the presence of an N-acyl steering group to attain high enantioselectivity [4] and works best when pure enamine isomers are used.[4b] Recently, improved catalytic systems were reported to attain high selectivity with (E/Z) mixtures [2d, 4b, 5] and the methodology was further extended to unsubstituted enamines (3, Ar = H) [6] and their N-aryl derivatives. [7] On the other hand, the sensitivity of asymmetric hydrogenation to the steric bulk of the substituents surrounding the enamine moiety makes the synthesis of certain b -amino acids a significant challenge.[8] Herein, we present a new methodology based on the organocatalytic asymmetric hydrosilylation of enamines that allows a direct access to a range of b 3 -and b 2, 3 -amino acid derivatives for some of which other methods proved less satisfactory.We have recently developed an efficient procedure for the asymmetric reduction of prochiral N-arylketimines with trichlorosilane ( 95 % ee), catalyzed by Lewis-basic form-A C H T U N G T R E N N U N G amides, such as Sigamide (8).[9-11] The method was then extended to the reduction of a-chloro imines and successfully applied to an enantioselective synthesis of N-arylaziridines.[12] To further expand the scope, we have now turned to the synthesis of b-amino acids. Treatment of the b-ketoester/nitrile 1 a/2 a (R 2 = H, R 3 = Ph; Scheme 1) with p-anisidine produced enamines 3 a/4 a, which themselves cannot be reduced by Cl 3 SiH.[13] On the other hand, a slow equilibration of the E-and Z-isomers of enamines 4, observed by NMR spectroscopy, is likely to proceed through the imine form (5), the reduction of which with Cl 3 SiH can be envisaged. Because the enamine-imine equilibration is facilitated by Brønsted acids, traces of HCl in commercial Cl 3 SiH may have a beneficial effect on the reaction. Indeed, under standard reduction conditions (enamine (1 equiv), Cl 3 SiH (2 equiv), and 8 (5 mol %) in toluene at RT), [9,12] enamine 3 a afforded the amino ester (S)-6 a in 78 % yield and 92 % enantiomeric excess (ee); however, the reaction suffered from poor reproducibility, giving a wide distribution of

Enantioselective reduction of ketimines 6-10 with trichlorosilane can be catalyzed by the N-methyl valine-derived Lewis-basic formamide (S)-23 (Sigamide) with high enantioselectivity (< or = 97% ee) and low catalyst loading (1-5 mol %) at room temperature in toluene. The reaction is efficient with ketimines derived from aromatic amines (aniline and anisidine) and aromatic, heteroaromatic, conjugated, and even nonaromatic ketones 1-5, in which the steric difference between the alkyl groups R(1) and R(2) is sufficient. Simple nitrogen heteroaromatics (8a,b,d) exhibit low enantioselectivities due to the competing coordination of the reagent but increased steric hindrance in the vicinity of the nitrogen (8c,e) results in a considerable improvement. Cyclic imines 32d-d exhibited low to modest enantioselectivities.

The selective N-methylation of BOC-protected valine 1a with MeI and NaH in THF (i.e., in the presence of a free carboxyl group) has been attributed to the protection of the carboxylate by chelation to Na(+). An alternative mechanism, involving the formation of the carbene intermediate generated from MeI and its insertion into the N-H bond, has been ruled out by isotopic labeling.