6-bromo-6-deoxy preparation

K. Bock, C. Pedersen, and P. Rasmussen, Reactions of acylated pentoses and acylated methyl pentosides with dibromomethyl methyl ether. Preparation of bromo-deoxy-pentoses, J. Chem. Soc., Perkin I, (1973) 1456-1461. 

Diels and Stephan173 treated the benzoate of 3-hydroxy-2-butanone with bromine, and obtained crystalline 1-bromo- and 1,1-dibromo- derivatives. With dilute alkali, these formed 4-deoxy-DL-gZycero-tetrulose and 4-deoxy-DL-erythrosone respectively. Both compounds gave with phenylhydrazine 4-deoxy-DL-erythrose phenylosazone, which had previously been prepared from the corresponding aldotetrose.174... 

The bromodeoxyaldonolactones have been used for the preparation of aminodeoxy aldonic acids and aminodeoxy sugars via azido derivatives (45,46). Likewise, a- and /J-aminopolyhydroxy acids have been prepared by treatment of the bromodeoxyaldonolactones with liquid ammonia (47). Thus, 3-amino-3-deoxy-D-threonic acid and 3-amino-3-deoxy-D-arabin-onic acid (40b) were obtained from 2-bromo-2-deoxy-L-threono- or D-xy-lono-1,4-lactone (38). It was shown that 2,3-epoxy carboxamides (namely, 39) are intermediates of the reaction. Heating at 90° for long periods led to the 3-amino-3-deoxyaldonamides, which upon acid hydrolysis yielded the corresponding aldonic acids. 

Improvement to the Reformatsky reactions was achieved (53) by the use of a highly activated zinc - silver couple dispersed on the surface of graphite. T reatment of protected aldono-1,4-lactones 10b or 25b and 1,5-lactones 51a or 51b with a Reformatsky reagent prepared from a-haloesters or alkyl 2-(bromomethyl)acrylates resulted in the formation of the corresponding 3-or 4-glyculofuranos (or pyranos)onates 49a,b-50a,b, or 52a,b, respectively, under mild conditions (— 40 ° to 00) and in very good yields. Ethyl 2-deoxy-2-fluoro (and 2-bromo)-a-D-wa o-3,6-furanos-3-octulosonate derivatives were also obtained. 

A number of enantiomerically pure chiral building-blocks, such as 292-294, have been prepared (270,271) by zinc-copper cleavage of 5-bromo-5-deoxy-2,3-0-isopropylidene-D-ribono-1,4-lactone, followed by reduction. Similarly, from the 5-iodo lactone analogue the enoic acid 295 was obtained by reaction with zinc/silver-graphite (272). 

The most attractive approach for the 2-deoxy-p-glycosides starts with 2-bromo-2,6-dideoxyhexopyranosyl bromides (2 ) such as These are available regio- and stereo-specifically from readily accessible and simple precursors by reaction with dibromomethyl methyl ether (DBE) (22, 2 ). In principle, the formation of related compounds may be anticipated by the addition of bromine to glycal precursors. Previous studies (24-27). however, proved these processes to yield several isomers which renders this approach of little preparative value. 

Various cis-ot,g-epoxycarbonyl compounds are stereoselectively prepared via g-bromo-g-hydroxycarbony1 compounds by application of this Sn(ll) mediated aldol reaction to a-bromocarbonyl compounds (22). Also this reaction is employed for the stereoselective synthesis of 2-amino-2-deoxy-D-arabinitol. 

The principle of the reactions between aldonolactones and HBr-HOAc is illustrated in Scheme 1 (entries I and II), and the mono- and di-bromodeoxylactones prepared in this way are listed in Table 1. The 2-bromo-2-deoxy-D-erythrono-and D-threonolactone can be prepared analogously to the L-isomers [11] from the salts of D-threonic and o-erythronic acid [ 12], respectively. The former can be prepared by oxidative degradation of D-xylose following an analogous procedure described by Humphlett [13]. 

Similarly, 5-bromo-5-deoxy-D-lyxonolactone gave the potassium L-ribonate, exclusively, when treated with a strong solution of potassium hydroxide [27]. The method was also used to prepare L-lyxonolactone from D-ribonolactone [27]. 

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