Unsymmetrical benzoin

By the use of 1 mol each of two different aldehydes, an unsymmetrical or mixed benzoin is obtained, for example ... 

Symmetrical and unsymmetrical benzoins have been rapidly oxidized to benzils in high yields using solid reagent systems, copper(II) sulfate-alumina [105] or Oxone-wet alumina [105, 106] under the influence of microwaves (Scheme 6.32). Conventionally, the oxidative transformation of a-hydroxy ketones to 1,2-diketones is accomplished by reagents such as nitric acid, Fehling s solution, thallium(III) nitrate (TTN), ytterbium(III) nitrate, ammonium chlorochromate-alumina and dayfen. In addition to the extended reaction time, most of these processes suffer from drawbacks such as the use of corrosive acids and toxic metals that generate undesirable waste products. 

Subsequently, the concept was extended to selective donor molecules. With 2-chlorobenzaldehyde as the selective acceptor a vast variety of unsymmetrical benzoins was accessible, among which 41d-41f were obtained selectively, proving that4-(trifluoromethyl)benzaldehyde, 4-bromobenzaldehyde, and 3-cyanobenzal-dehyde were selective donor substrates for BFD H281A under these reaction conditions [67, 69]. 

Importantly, TV-carbamoyl derivatives of primary amines obtained from photolabile benzoins exist in varying proportions as cyclic hydroxyoxazolidinone tautomers. Therefore, the preparation of TV-carbamoyl derivatives of benzoins is applicable only for secondary amines and TV-alkylated amino acids. 244 At basic pH unsymmetrical benzoins, such as 3,5-dimethoxybenzoin, their mixed carbonate and carbamate derivatives, tend to equilibrate to the isomeric forms. Nevertheless, in TFA and aqueous solutions at pH 8 the structural integrity is fully maintained. 244 Preparation of 3,5-dimethoxybenzoin-derived carbamates of secondary amines and amino acids can be mediated by either CDI/methyl triflate in ni-tromethane 246 or 4-nitrophenyl chloroformate/DMAP in dry THF. 244 ... 

Benzoin condensation.1 The benzoates of cyanohydrins of aromatic aldehydes undergo benzoin condensation with an aromatic aldehyde in 50% NaOH/C6H6 in the presence of a phase-transfer catalyst, benzyltriethylammonium chloride. Theoretically two symmetrical and two unsymmetrical benzoins are possible, but in practice only one unsymmetrical benzoin is formed, that in which the carbonyl group is adjacent to the benzene ring substituted by the more electron-donating group. 

Unsymmetrical or mixed benzoins may be obtained in good yield from two different aldehydes ... 

Benzoin 23 could be used instead of benzil 22, provided that the microwave-assisted cyclocondensation is performed on inorganic support (silica gel or alumina) under solvent-free conditions [40]. A related diversity-oriented approach towards imidazoles utilized the cyclocondensation of unsymmetrical keto-oximes with aldehydes in the presence of NH4OAc [41] (Scheme 16). Hydroxyimidazoles 24 were formed in the cyclization step and... 

More recent evidence from our laboratory indicates that when the thiazolium salt is first converted totally to the unsymmetrical and symmetrical syn-anti dimers (13C NMR indicated the presence of both configurations), addition of benzaldehyde to this solution cannot form HBT, whereas addition of benzaldehyde to a mixture that still contains monomeric thiazolium salts indeed forms this HBT adduct57. Such experiments tend to confirm that it is the enamine rather than the double enamine (the benzaldehyde adduct of the syn-anti dimers) that participates in thiazolium salt catalyzed benzoin condensations. 

The 4,5-di(thien-3-yl)-l,3-dithiol-2-one 517 was prepared from the thiophene-3-carboxaldehyde 513 which was first converted into the benzoin derivative 514. Subsequent Appel s reaction of the latter with PPhs and carbon tetrachloride afforded the chloride 515, which underwent reaction with potassium ethyl xanthate to form 516, from which the l,3-dithiol-2-one derivative 517 was obtained in overall 50% yield from 514 upon treatment with HBr/ AcOH (Scheme 74). The unsymmetrical 522 was prepared by transformation of the carboxylic acid 518 to the corresponding acid chloride which took part in a Friedel-Grafts reaction with thiophene in the presence of AIGI3 to... 

The anion of the adduct of TMS-CN with benzaldehyde reacts with aldehydes and ketones to form acyloin silyl ethers, by way of a 1,4-0-silyl rearrangement (Scheme 10). This method gives a-hydroxy ketones in excellent yield (80-90%) and allows the selective synthesis of unsymmetrical benzoins. ... 

Instead of using a-haloketones, an unsymmetrical benzoin can be utilized as starting material for the Bischler-Mohlau indole synthesis. RWJ 68354, a potent inhibitor of the p38 MAP kinase, was prepared via a variation of the Bischler-Mohlau indole synthesis under mild conditions with 55% isolated yield only 2-3% regioisomer could be isolated from the mother liquor. ... 

An interesting extension of this method involves the reaction of Af-silyl oxyketene imines derived from cyanohydrins (Scheme 19) [81]. By judicious selection of the protecting group on the oxygen, highly functionalized (3-hydroxy cyanohydrins can be accessed with high levels of enantio- and diastereoselectivity. These products can then be transformed into a diversity of structural motifs (amines, aldehydes, imines, ketones) important for the synthesis of polyketide and other classes of natural products. In addition, the ethers can be easily converted to enantiomerically enriched unsymmetrical benzoins, thus revealing the synthetic equivalency of A-silyl oxyketene imines as acyl anions (Scheme 19). 

Using sohd reagent systems, copper (II) sulfate-alumina, or oxone-wet alumina symmetrical and unsymmetrical benzoins can be rapidly oxidized to benzils in high yields under the influence of microwaves (Varma et al., 1999). 

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