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SYNTHETIC COMMUNICATIONSV
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Scheme 1. Attempted synthesis of allene 8. Reagents and conditions: (a) LiBr, n-BuLi, MsCl, THF,
–78 ꢀC-rt; (b) CuBr, LiBr, THF, rt; (c) n-BuLi, THF, –78 ꢀC; (d) THF, –78 ꢀC-rt.
provider.[25,26,32–36] We first chose TBS and Bn group as the leaving group.
Intermediate 10 was prepared from chiral propargylic alcohol 9 (93% ee) by previously
reported method.[15] The reaction of Bn-protected chiral propargylic alcohol 11 with
Garner aldehyde 7 provided intermediate 12. LiAlH4 reduction of propargylic alcohol
11 gave a mixture of allenic alcohol 13 and allylic alcohol 14, the yields of which
depended on the reaction conditions. First, the choice of reaction solvent was very
important. When the solvent was THF, the yields of both 13 and 14 were low and
some unidentified byproducts were formed. When diethyl ether was used, only 13
and 14 were obtained. The ratio of 13 to 14 depended on the reaction temperature and
time. If the temperature was very low (–41 ꢀC), the reaction with excess amount of
LiAlH4 was not completed and some of the starting material 10 could be recovered.
When the reaction was carried out at ꢁ15 ꢀC for 3 h, then raised to room temperature
for 0.5 h, allenic alcohol 13 was obtained as the major product. Conversely, when the
reaction was carried out at ꢁ15 ꢀC for 0.5 h, then allowed to warm to room temperature
for 3 h, allylic alcohol 14 was formed as the major product. The amount of LiAlH4 was
also very important. It was found that 1.5-2.0 equiv. of LiAlH4 was suitable to form the
allenic alcohol, and 2.5–3.0 equiv. of LiAlH4 was suitable to form the allylic alcohol.
The stereochemistry of allene in compound 13 from 10 or 12 was proposed according
to the mechanism shown in Scheme 2: hydroxyl-directed trans-hydrometalation fol-
lowed by anti-elimination. These type of directed reduction-elimination reactions were
presented by Cowie,[25a] Olsson[25b] and VanBrunt.[26]
LiAlH4 reduction of 12 provided 13 and 15 simultaneously, but this reaction need
stronger conditions than that of reduction of 10. Because 12 and 13 have the same
polarity, it is very difficult to separate them by chromatograph. So, compound 12
should be completely consumed by the reduction. It required the reaction to be carried
out at room temperature for at least two hours. The highest yield of allene 13 by reduc-
tion of 12 was 55% accompanied by 20% of allylic alcohol 15. We also tried OMOM
group as leaving group, but the yield of allene 13 was much lower than OTBS and OBn