Deoxygenative [1,2]-hydride shift Rearrangements in nucleoside and sugar chemistry: Analogy with the [1,2]-electron shift in the deoxygenation of Ribonucleotides by ribonucleotide reductasesi

• Published in: Journal of organic chemistry Vol. 72; no. 22; pp. 8216 - 8221
• Main Authors: Robins, Morris J., Nowak, Ireneusz, Wnuk, Stanislaw F., Hansske, Fritz, Madej, Danuta
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 26.10.2007
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; SYNTHETIC UTILITY; ACID RELATED-COMPOUNDS; ANTI-HIV ACTIVITY; BETA-ELIMINATION REACTIONS; CHAIN DEOXY SUGARS; LITHIUM TRIETHYLBOROHYDRIDE; PREPARATIVE APPLICATIONS; PARA-TOLUENESULFONATES; GRIGNARD-REAGENTS; <1,2>-HYDRIDE SHIFT
• ISSN: 0022-3263
• DOI: 10.1021/jo071102b

A variant of the semipinacol rearrangement that was observed in our laboratory has been applied to the synthesis of several furanose and pyranose derivatives. The process consists of an "orchestrated" [1,2]-hydride shift with departure of a leaving group from the opposite face. Transient formation of a C=O group is followed by rapid transfer of a hydride-equivalent from the same face from which the leaving group departed, which results in double inversion of stereochemistry at the two vicinal carbon atoms. Treatment of 2(')-0- and 3(')-O-tosyladenosine with lithium triethylborohydride in DMSO/THF gave the respective 2(')- and 3(')-deoxynucleoside analogues with beta-D-threo configurations. Identical treatment of 5(')-O-TPS-2(')-O-tosyladenosine gave 9-(5-O-TPS-2-deoxy-beta-D-threo-pentofuranosyl)adenine. The same [1,2]-hydride shift and stereochemistry with the 5(')-OH and 5(')-O-TPS compounds demonstrated the absence of remote, hydroxyl-group participation. Application of this process to other nucleoside 2(')-O-tosyl derivatives gave the 2(')-deoxy-threo compounds in good yields. The reaction-rate order was OTs approximate to Br >> Cl for 2(')-O-tosyladenosine, 2(')-bromo-2(')-deoxyadenosine, and 2(')-chloro-2(')-deoxyadenosine (all with beta-D-ribo configurations). Analogous results were obtained with mannopyranoside derivatives with either 4,6-O-benzylidene protection or a free OH group at C4. Deuterium labeling clearly defined the stereochemical course as a cis-vicinal [1,2]-hydride shift on the face opposite to the original cis OH and OTs groups followed by hydride transfer from the face opposite to the [1,2]-hydride shift. Synthetic and mechanistic considerations are discussed.