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.
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.
Robins
Morris J
MJ
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602-5700, USA. morris_robins@byu.edu
Nowak
Ireneusz
I
Wnuk
Stanislaw F
SF
Hansske
Fritz
F
Madej
Danuta
D
D018360:Crystallography, X-Ray; D003854:Deoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D004583:Electrons; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D012264:Ribonucleotide Reductases / Q000737:chemistry*; D012265:Ribonucleotides / Q000737:chemistry*; D013237:Stereoisomerism
D003854:Deoxyribonucleotides; D012265:Ribonucleotides; D012264:Ribonucleotide Reductases