1646
J. Org. Chem. 1992,57, 1646-1647
Organocerium Additions to 2'-Deoxy-3'-ketonucleosides Steven L. Bender* and Kristofer K. Moffett Department of Chemistry, University of California, Zrvine, California, 92717 Received January 2, 1992
Scheme I
Summary: Organocerium reagents undergo efficient and highly diastereoselective carbonyl addition reactions with 2'-deoxy-3'-ketonucleosides derived from thymidine, 2'deoxycytidine, and 2'-deoxyadenosine. I OH
k
-78 'C
In connection with a project directed toward the syn1 2 3: R = CH3 thesis of new oligodeoxynucleotide analogues, we desired 4: R CH=CHz an efficient and direct method for C-C bond formation at 5: R C S T M S C-3' of 2'-deoxynucleosides. Among the various options that are organometallic additions to 3'-ketoSerles nucleosides 2 appeared to be an attractive possibility. At c: Pg = t-BuPh,Si b: Pg = f-BuPh,Si a: Pg = Ph3C the outset of this work, however, only the ketothymidine B= B= B= 0 2a was known in the literature,3 and the well-d~cumented~~~ sensitivity of 2a toward the &elimination of thymine had, H'NKPh I with two exceptions: thwarted previous efforts to add organometallic reagents to the carbonyl function, Herein we report that organocerium reagents, which have become established as nonbasic highly-nucleophilic reagents for carbonyl additions? undergo facile additions to ketothymidine 2a. In the course of our investigation, Robins diastereomer, within the limits of detectability. Difference and Samano reported that the Dess-Martin periodane7was NOE experiments on adduct 3b clearly established the a superior oxidant for the preparation of ketonucleosides,8 configuration at C-3' to be as shown, in agreement with and this observation has allowed us to extend the scope e~pectation.~ of our method. Specifically, the previously unreported Our general procedure for the addition of organocerium 3'-kete2'-deoxy adenosine 2b and 3'-kete2'-deoxy cytidine reagents to the ketonucleosides 2 is as follows: CeC13.7H20 2c,despite their extreme propensity toward &elimination, (6 equiv) was dried at 140 "C under vacuum (
