Heck reaction, regioselectivity

Pei, W., Mo, J. and Xiao, J. (2005) Highly regioselective Heck reactions of heteroaryl halides with electron-rich olefins in ionic liquid. J. Organomet. Chem., 690, 3546-51. 

Complete / -regioselective Heck reaction has been reported using fert-butyl 3-iodo-l//-indole-1-carboxylate (III-62Boc) with electron-poor alkenes Yue and Larock [231], Yue et al. [232], Putey et al. [233], Mitsudo et al. [234], Della Sala et al. [235]. 

In Chap. 5, a presentation of the related regioselective Heck reaction of heteroaromatic tosylates is given. The work was conducted in collaboration with Dr. Anders Thyboe Lindhardt, Dr. Mouloud Dekhane from AstraZeneca, and B.Sc. Julie Groulefif. 

Scheme 1.21 Polar solvents in the regioselective heck reaction of aryl halides...

In the following, the regioselective Heck reaction of heteroaromatic tosylates and electron rich olefins will be presented and discussed. This protocol constitutes the first general strategy for the palladium catalyzed olefination of pyridyl tosylates obtaining perfect a-regioselectivity. 

Table 5.2 Regioselective heck reaction utilizing W-vinylacetamide...

Next, tosylated hydroxypyrimidines were tested in the regioselective Heck reaction using NVA and n-butyl vinyl ether in order to investigate the influence of the heteroaromatic core system on the catalytic outcome (Scheme 5.3). Similar yields of the vinylated pyrimidines compared to the pyridine equivalents were achieved indicating a robust catalytic system. Even a double Heck reaction could be accomplished yielding 56 in 36 % corresponding to an average of 60 % yield of each vinylation. 

Results and Discussion Table 5.3 Regioselective heck reaction utilizing -butyl vinyl ether... 

Scheme 5.3 Pyrimidyl tosylates in the regioselective heck reaction. Reprinted (adapted) with permission from Chem. Eur. J. 2009, 15, 5950. Copyright 2009 Wiley-VCH Verlag GmbH Co. KGa. Weinheim...

Further developments of the regioselective Heck reaction between aryl sulfonates and electron rich olefins will be presented in the following chapter. 

As described in Sect. 1.7.1 the regioselective Heck reaction, producing the a-arylated olefins selectively, proceeds by a pathway involving a vital cationic palladium(II) intermediate. This pathway can be favored by a number of factors, including triflate based electrophiles and bidentate ligands (see Sect. 1.7.1). 

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