Heck adduct

Without the alkoxy substituent on the olefin, steric effects prevail. The Heck adduct 164 was isolated when 2-chloro-3-pivaloylamidopyridine (163) was allowed to react with an excess of styrene [129], Steric effects can play a major role in the regioselectivity of these reactions. 

Both 2-bromothiophene and 3-bromothiophene have been coupled with allyl alcohols to make thienylated a, 3-unsaturated ketones [124], Iodothiophenes were more reactive than the corresponding bromides, whereas the chlorothiophenes were unreactive. As expected, 2-bromothiophene was two to three times more reactive than 3-bromothiophene. In addition to the expected Heck adduct 149, the reaction of 2-bromothiophene 148 with l-methylprop-2-en-l-ol also resulted in the regiosmer 150. 

For the Heck reactions involving halothiazoles, 2-bromo- and 4-bromothiazoles tend to give resinous products, whereas some 5-bromothiazoles may form the desired Heck adduct with... 

Palladium-catalyzed reaction of bromo dienes 39 was complete after a few hours, and afforded spirocycles 40a and 40b as single regio- and stereoisomers (Scheme 12). The Heck spirocyclization reaction is regioselective, giving five-membered heterocycles. In addition, it is stereoselective because the Heck adducts were obtained as single geometric isomers [60]. 

For the Heck reactions involving halothiazoles, 2-bromo- and 4-bromothiazoles tend to give resinous products, whereas some 5-bromothiazoles may form the desired Heck adduct with appropriate olefins. With respect to the heteroaryl Heck reaction using a thiazole as a coupling partner, the addition occurs regioselectively at the electron-rich C(5) position, whereas it occurs at C(2) for benzothiazole. 

More recently, a tandem Heck/allylic substitution cascade was used as a route toward various lactams. The reaction of 631a,b with 2-isopropenyl bromide in the presence of Pd(OAc)2 and (o-tolyl)3P gave the Heck adduct 632 that reacted further with H-Pd-Br to give the 71-allylpalladium complex 633. Intramolecular attack of the amide anion on the 7i-allyl complex followed by reductive elimination of Pd(0) afforded 634a,b in 77 and 75% yield, respectively (03OL259). Other vinyl bromides were also examined and found to give substituted pyrrolidinones and piperidones in moderate to good yields (50-82%). 

The IMI approach for the synthesis of DFBP starts from p-bromofluorobenzene (BFB) and substituted styrene or acrylate at a ratio of 2 1 [30]. The reaction involves the formation of a double-Heck adduct (yield > 90 % with a regioselectiv-ity of 94 % at the C-2 of the acrylate) then catalyzed oxidative-cleavage (95 %) (Scheme 9). 

Oxidative Heck reaction. Homoallylic alcohols react with various boronic acids in the presence of Pd(TFA)2, bathophenanthroline and benzoquinone as reoxidant to conventional Heck adducts (eq 11). The E stereoisomer is highly favored. ... 

As the substrate-directed Heck-Matsuda reactimi promoted a significant increase in structural complexity, we envisioned that VPC01091 (131) could be synthesized in a straightforward manner starting from the Heck adducts of the reaction between 112 and the corresponding aryldiazonium salt (Scheme 31). 

In his initial review on the scope of the reaction, Heck reported the use of a variety of relatively simple aryl, heteroaryl and vinyl halides. For example, exposure of bromopyridine 48 to alcohol 49 gave ketone 51 in good yield, following tautomerization of the initial Heck adduct 50. 

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