Cross Metathesis of alpha-Methylene Lactones II: gamma- and delta-Lactones

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/orlef7/asap/abs/ol070574+.html

Ravinder Raju, Laura J. Allen, Tri Le, Christopher D. Taylor, and Amy R. Howell*

Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060

This is the other paper that was published online the same day as the Prof. Cossy's paper on cross metathesis (CM) reaction of alpha-methylene lactone and alkenes (previous post). The Howell group previously reported studies on CM reaction of alpha-methylene-beta-lactones with alkenes using Grubbs' 2nd generation catalyst (3) which was found to proceed to give cross products favoring Z-stereochemistry exclusively.

Therefore in commencing the current studies, catalyst 3 was initially used. However, it was found that when alpha-methylene-gamma-butyrolactone 5 was subjected to 3 and 1-acetoxy-9-decene, only alkene isomerization product 6 was obtained. This is in contrast to the Cossy group's result that the reaction was incomplete giving a mixture of both cross product and isomerization product, although the alkene cross partner in that study was 4-methyl-1-pentene. (See the previous post, Table 1, entry 3). Because catalyst 3 did not perform the desired transformation, catalyst 4 was explored. The results are summarized in the table below.

To suppress the formation of 6, 2,6-dichlorobenzoquinone was added as an additive along with catalyst 4. The combination of the two reagents were found to give excellent yield of the desired product (5) when 0.10 equiv of benzoquinone was used coupled with successive addition of the catalyst in two portions in the total of 10 mol %, while formation of 6 was completely suppressed (entry 8). When only 5 mol % of catalyst 4 was used, the reaction would not go to completion (entry 7) and this is in agreement with the results from the French group.

Next, a couple of alkenes were looked at using the optimal condition with catalyst 4 and additive 7.

In general, reactions proceeded as expected giving cross products favoring E-stereochemistry. For entries 5 and 6, yields were lower mainly because reactions did not proceed to completion.

The attention was then turned to CM reaction of delta-lactone 2. It was found that CM reaction using both catalysts 3 and 4 did not afford any desired product 9. When the reaction was conducted at higher temperater (toluene), only isomerized product 10 was obtained. Additive of additive 7 did suppress the formation of 10 but still did not produce any 9.

Thinking that substrate may complex with the catalyst to form unreactive species, Lewis acid Ti(Oi-Pr)4 (11) was added to reaction in toluene, complete consumption of SM giving only 10 resulted. When HOAc was used as additive, 54% of 9 was produced while 10 was suppressed. But this was not efficient as 10 mol % of catalyst was needed and reaction only proceeded to the maximum of 54% after 36 h. Although, efficient conversion of lactone 2 to 9 failed, the results seem to suggest that there may be an optimal combinations of additives and catalysts to be found. And this warranted more future studies of these systems.