Hoveyda-Grubbs’ second-generation catalyst

The same catalyst system works well in hetero-allylic asymmetric alkylations (h-AAA Scheme 1-16). Substrates such as enol esters 163 provide entry to nonracemic esters of allylic alcohols. Remarkably, competing 1,2-addition and/or acyl transfer were not issues yields are good (80-99%). In these cases, catalyst loading can go as low as 0.8%, and ee s are mostly >95%. Additional chemoselectivity has been noted in the case of cinnamyl ester 163, where the desired Sn2 AAA takes place without competing Cu-catalyzed 1,4-addition to the enoate. This sets the stage for a subsequent metathesis (GH-2 = Grubbs-Hoveyda second-generation catalyst) en route to butenolide 164. 

Fig. 3 Olefin metathesis catalysts Schrock tungsten (Cl) and molybdenum (C2) alkylidene complexes, Grubbs first- (C3) and second-generation (C4) catalysts, Hoveyda-Grubbs second-generation catalyst (C5), and Grubbs third-generation catalyst (C6)...

Figure 28 Hoveyda-Grubb s first and second generation catalysts.

Figure 2 Metathesis catalysts Grubbs first-generation catalyst (5), Grubbs second-generation catalyst (6), Hoveyda—Grubbs catalyst (7), and Grubbs—Nolan catalyst (8).

HGII Hoveyda-Grubbs second generation catalyst... 

It is noteworthy that these five syntheses used four different metathesis catalysts in the key alkene forming step. For the cyclization of 7, the use of the Grubbs first generation catalyst Gl, that couples terminal alkenes but tends not to interact with internal alkenes, was probably critical to success. The Hoveyda catalyst H2 is more expensive than the Grubbs second generation catalyst G2, but can often be effective in appHcations in which G2 is sluggish. The Schrock Mo catalyst is less user fiiendly than the (relatively) air and moisture stable Ru catalysts, but is very reactive. 

With regards to the initiation of ROMP kinetics using DCPD as the monomer, the Hoveyda-Grubbs second-generation catalyst proved to be significantly more reactive with over 60% of DCPD conversion observed within the first 5 minutes. The second-generation Grubbs catalyst exhibited the slowest reaction kinetics in bulk polymerization, an observation which is in contrast with the performance observed for similar reactions performed in solution (25,40). 

Cinnamyl bromide 24 and the iodocarbohydrate 23 are combined in a zinc-mediated fragmentation/allylation reaction to afford a highly functionalized 1,7-diene, which is then treated with Hoveyda-Grubbs second-generation catalyst to produce a mixture of diastereomeric cyclohexenes 25 (35% yield) and 26 (32% yield). From the major isomer 25, subsequent Overman rearrangement, dihydroxylation, and deprotection afford the natural product pancrastistatin (28) (Scheme 3.10). 

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