Hydroxyalkyl-dehydrogenation

In order to assess the synthetic potential of enzymatic oxidations for organosilicon chemistry, the (hydroxyalkyl)silanes 95, 97 and 99 have been studied for their oxidation (dehydrogenation) with horse liver alcohol dehydrogenase (HLADH E.C. l.l.l.l)79. For this purpose, these compounds were incubated with HLADH in a TRIS-HC1 buffer/THF system in the presence of NAD+. As monitored spectrophotometrically (increase of absorbance of the NADH formed), the (2-hydroxyethyl)silane 97 and the (3-hydroxypropyl)silane 99 were better substrates for HLADH than ethanol, whereas the related (hydroxymethyl)silane 95 was not a substrate under the experimental conditions used. Interestingly, the corresponding carbon analogue 101 was found to be accepted by HLADH. On the other hand, the (2-hydroxyethyl)silane 97 was found to be a better... 

Based on these results, attempts have been made to apply enantioselective dehydrogenations with horse liver alcohol dehydrogenase HLADH, E.C. 1.1.1.1), in the presence of NAD+, for kinetic resolution of the isomeric (hydroxyalkyl)silanes rac-105, rac- 107... 

However, a considerable difference should be noted between a-hydroxyalkyl nitrilium ions 24 which contain an intramolecular nucleophilic center (OH group), and N-alkylnitrilium ions 26 which are the intermediates of a Ritter reaction45. The transformation of ions 24 into the N-acyliminium ions 25 (equation 11) is evidently an intramolecular rearrangement (see Sections V.B and V.C), while the nitrilium salts 26 can be converted into ions 25 only by an oxidative dehydrogenation of amides 273 (equation 12). 

Hydroxyalkylation. The complex of AgOTf with (5)-BlNAP is used in enantioselec-tive reaction of 3-trimethylsilyl-l,4-cyclohexadiene with ArCHO. It is important to note the regiochemical aspect in its application to unsymmetrical pronucleophiles. The products are converted into chiral benzhydrols on dehydrogenation with DDQ. 

The sequence of this reaction was established by the isolation of intermediates, the distribution of substituents in the products and C-labeling. The first step is the Michael addition of the amine to the enone system 80 with formation of P-amino ketones 81. They cyclize to give 82 with intramolecular hydroxyalkylation via the protonated C=0 group. Dehydration leads to 1,2-dihydroquinoline 83, which on dehydrogenation affords quinoline 84. 

The acyl-generation reaction, Eq. (8), has been visualized as a reductive acylation of protein-bound lipoic acid. As will be seen below, this reaction is now belitwod to consist of two steps an oxidation of the 2-hydroxyalkyl-thiamine pyrophcjsphatc to 2-aoylthiaminc pyrophosphate with a concomitant reduction of bound lipoic acid, and a transfer of (he acyl group of 2-acylthiamine pyrophosphate to the bound dihydrolipoic acid (Das el al., 19(il). An enzymatic component which contains bound lipoic acid and apparently catalyzes reactions (8) and (9) has been isolated from the E. mli pyruvate dehydrogenation complex (Koike and Reed, 1961). This component, designated lipoyl-Ea in Fig. 1, has been tentatively named lipoic reductase-transacetylase. 

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