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 reductases

• 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, DC American Chemical Society 26.10.2007
• Subjects: Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Crystallography, X-Ray; Deoxyribonucleotides - chemical synthesis; Deoxyribonucleotides - chemistry; Electrons; Exact sciences and technology; Kinetics and mechanisms; Models, Molecular; Molecular Conformation; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Oxidation-Reduction; Preparations and properties; Reactivity and mechanisms; Ribonucleotide Reductases - chemistry; Ribonucleotides - chemistry; Stereoisomerism; Deuterium; Configuration; Isotope labelling; Lithium; Stereochemistry; Tetrahydrofurane; D-threo stereoisomer; Transient species; Methyl sulfoxide; Chlorine Organic compounds; Deoxygenation; Hydroxyl group; Reaction mechanism; Nucleoside; Bromine Organic compounds; Chemical synthesis; Protection; Ribonucleotide; Adenine derivatives; Chemical rearrangement; Adenine; Oside; Organic bromine compounds; D-ribo stereoisomer; Hydride transfer; Purine base; Reaction rate; Organic chlorine compounds; Deoxyadenosine; Analog; Threo stereoisomer; Nucleotide
• ISSN: 0022-3263; 1520-6904
• 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'-O- 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 approximately 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.