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6852886 
Journal Article 
THERMAL [1,7]-SIGMATROPIC SHIFT OF PREVITAMIN-D3 TO VITAMIN-D3 - SYNTHESIS AND STUDY OF PENTADEUTERIO DERIVATIVES 
Okamura, WH; Okamura, WH; Elnagar, HY; Elnagar, HY; Ruther, M; Ruther, M; Dobreff, S; Dobreff, S 
1993 
Yes 
Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 
58 
3 
600-610 
WOS:A1993KK26300011 
Specifically pentadeuteriated previtamin D3 11 has been synthesized to impart thermal stability to the otherwise labile material. A 12-step synthesis of the trideuteriated A-ring 14b from p-methoxyphenol was developed and employed the addition of (methyl-d3)magnesium iodide to either the keto thiomethylene intermediate 23 or the keto dioxane 27. The enantiomerically pure trideuterio A-ring (-)-14b was then coupled with the deuteriated CD fragment 13b followed by hydrogenation to afford pentadeuteriated previtamin D3 11. A primary deuterium kinetic isotope effect (KIE) study of the [1,7]-sigmatropic hydrogen migration in the conversion of previtamin D3 to vitamin D3 indicated a more ''normal'' primary deuterium isotope effect (as compared to a previously reported literature value of approximately 45). At 80-degrees-C, a k(H)/k(D) for the previtamin D3 to vitamin D3 isomerization was determined to be approximately 6.2. At 25-degrees-C, this [1,7]-sigmatropic hydrogen migration proceeds with a k(H)/k(D) Of approximately 11.4. The reversible, first-order [1,7]-sigmatropic hydrogen shift of previtamin D3 to D3, determined over the temperature range 60.1-85.5-degrees-C is characterized by the following activation parameters: log A(H) = 8.8 and E(a)H = 19.6 kcal/mol. Deuteriated pre-D3, which rearranges over this temperature range, is characterized by the activation parameters log A(D) = 9.5 and E(a)D = 21.9 kcal/mol.<