Development of an effective chiral auxiliary for hydroxyalkyl radicals.
The development of an effective chiral auxiliary for hydroxyalkyl radicals is delineated. Both the 2-tetrahydropyranyl (THP) and tri-O-benzyl-2-deoxy-alpha-D-glucopyranosyl (GLU) auxiliaries resulted in diastereoselective radical additions to methyl acrylate at -78 degrees C (ds = 6/1 and 11/1, respectively). The developing stereochemistry at the radical center was completely under auxiliary control. Correlation experiments showed that the D-GLU auxiliary led to attack on the radical Si-face. The selectivity of these radical additions dropped-off considerably when the more reactive 2-nitropropene trap was employed. Computational studies suggested that the observed facial selectivity was due primarily to entropic factors in the transition state but that a smaller temperature-dependent enthalpic contribution was also involved. It was hypothesized that incorporation of a quaternary center at C-6 (THP numbering) would restore the facial selectivity with more reactive radical traps by restricting the orientations available to the incoming alkene. In the event, the trans-6-tert-butyltetrahydropyranyl (tBu-THP) auxiliary resulted in very good diastereoselection with 2-nitropropene (ds = 35/1 at -78 degrees C, 15/1 at 0 degrees C, and 8/1 at RT) as did the tri-O-benzyl-6,6-dimethyl-2-alpha-D-deoxyglucopyranosyl (diMe-GLU) auxiliary during additions to ethyl alpha-trifluoroacetoxyacrylate (ds = 10/1 at 0 degrees C). A protocol for recovery of the sugar-derived chiral auxiliaries was also established. This work sets the stage for the development of a novel approach to 1, 3, 5.(2n + 1) polyols based on iterative radical homologation as well as the application of these pyranosidic auxiliaries to other synthetically important reactions.
Garner
Philip
P
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA. ppg@po.cwru.edu
Anderson
James T
JT
Cox
Philip B
PB
Klippenstein
Stephen J
SJ
Leslie
Ray
R
Scardovi
Noemi
N
D000438:Alcohols / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D006868:Hydrolysis; D017665:Hydroxyl Radical / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
D000438:Alcohols; D000475:Alkenes; D002241:Carbohydrates; D017665:Hydroxyl Radical