Highly diastereoselective titanium(II)-mediated cyclizations of 1,7-(silyloxy)enynes

2008 ARKIVOC  
Cyclization of 1,7-(silyloxy)enynes with Ti(i-PrO) 4 and n-BuLi yields 6-membered cyclic siloxanes in moderate to good yields. The reaction is highly diastereoselective (typical d.r.'s >15:1). Results and Discussion Our initial studies focused on readily accessible 1,7-(silyloxy)enyne 2, which was prepared by silylation of alcohol 1 4 with bromodiisopropylhexynylsilane (Scheme 1). 5 In our earlier work on the cyclization of 1,6-(silyloxy)enynes the combination of ClTi(OPr i ) 3 as the titanium
more » ... 3 as the titanium source with i-PrMgCl (two equivalents with respect to the Ti) at -40 ºC had proven optimal. Although these conditions resulted in cyclization of 2, there was a significant amount of unreacted starting material, and the isolated yields of 3 were never greater than ~35%. Although more starting material could be consumed by the addition of further equivalents of ClTi(OPr i ) 3 and the Grignard reagent after 3 hours, we viewed this approach as cumbersome and sub-optimal. Variation of temperature and solvents also failed to appreciably effect the levels of conversion and the combination of Ti(OPr i ) 4 /i-PrMgCl was also fruitless. Gratifyingly, turning to n-BuLi as the reductant provided increased reactivity and in the case of 2, cyclization provided the desired cyclic siloxane 3 in 70% yield as essentially a single diastereoisomer (d.r. >15:1). NOESY NMR experiments showed a strong correlation between the hydrogen adjacent the alcohol and the hydrogen adjacent to the methyl group, which strongly suggested that the reaction occurs with 1,3-syn stereoinduction. Desilylation using TBAF provided the alcohol 4 in quantitative yield. 6 General Papers ARKIVOC 2008 (xvi) 110-118
doi:10.3998/ark.5550190.0009.g11 fatcat:sm3osihw2rgfxiihmmsjahvadm