Highly Efficient Ruthenium Catalysts for the Formation of Tetrasubstituted Olefins via Ring-Closing Metathesis

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/orlef7/asap/abs/ol0705144.html

From Prof. Robert H. Grubbs' group at Cal Tech

This is another paper in the series studies on RCM to form tetrasubstituted-alkene-containing ring appeared recently in Org Lett ASAP. This is a second paper in March, following the other one that became a blog entry here. The authors continued to explore the effect on the ortho-substituents in NHCs group in Ru-center.

RCM reactions to form disub olefin work well using phosphine-based catalyst (ie. Grubbs I) and to form trisub olefin work well with NHC-based (ie. Grubbs II, 1). But for the tetrasub, it is still difficult.

In this paper, the authors continued discussion on the variations of substitution on o-position of aryl groups on NHC. Contrast to previous paper (as mentioned in previous post), the studies were conducted with mono substitution of the o-position on NHCs. As a result 5a-c and 6a-c were studied. The catalysts were subsequently screened with dienes 7 and 9.

The results of the screening with 7 are summarized in table and chart below. It was found that conversions with catalyst 5a-c were faster than 6a-c. And 5a and 6a performed better than other alkyl derivatives. NMR studies of 5a found a rapid initiation than 6a but quickly decomposed. This was thought to be due to build-up of ethylene in the system which deteriorated the catalyst by reacting with PCy3. In contrast, 6a initiated more slowly, but was longer-lived. However, when reaction of 9 using 6a was heated to 60 C (to assist initiation of the catalyst), it proceeded very efficiently to give 10 in less than 30 min. Subsequently, loading of 6a could be lowered to 2.5 mol% to accomplish RCM of 9 in >95% in 1 h.

X-ray structure of 6a was determined and was found to contain 91:9 mixture of syn- to trans-conformation of methyl groups in the o-positions of aryl groups. But it was not clear which was more reactive in RCM.

6a was then used to screen a number of substrates and was found to perform very well with all dienes, except 16 and 17.

In conclusion, 6a was discovered to be very reactive in RCM to form tetrasub-cycloalkene. 6a initiates more slowly than 5a but is more stable because of the lack of PCy3. However, initiation of 6a could be accelerated by heating reaction mixture. The mono o-substituted aryl groups on NHC open up the Ru center to facilitate the reaction more than the older generation of catalysts, making it more reactive to form tetrasub-alkene rings.