Heck reaction with conjugated compounds

Whereas inter- and intramolecular Diels-Alder reactions normally require electron-deficient dienophiles, the 67r-electrocyclization proceeds with a large vaiiety of substituents on a hexatriene. In one such approach, the intramolecular Heck-type reaction of a 2-bromo-1 -en-(ft> — l)-yne 66 is used as a trigger to initiate an intermolecular Heck coupling with an alkene to form the conjugated 1,3,5-hexatriene 67 which eventually cyclizes in a 67T-electrocyclic process (Scheme 3-21) [173]. In many cases, aromatization of the cyclohexadiene 68 formed primarily occurs to yield carbo- and heterobicyclic compounds of type 70 [173a,b]. But with alkyl ethenyl ethers the cyclohexadienes 69 can be obtained in moderate yields [173b]. 

In the last chapter we introduced the Heck reaction as a way to add nucleophiles to electrophilic alkenes. The details of the mechanism are discussed there. The reaction also occurs with allylic alcohols 218 and is a good way to make carbonyl compounds, particularly aldehydes, 219 as the alternative conjugate addition of an organometallic compound to an enal often shows poor regioselectivity (chapter 9). 

Sequential Heck reaction and hydrosilylation of carbonyl have been carried out with the Grubbs I catalyst. AUyUc alcohols can be S3mthesized via conjugated carbonyl compounds prepared from cross-metathesis in situ by reduction with j-Bu2AlH. An access to enantiomeric 2,3-dihydroxyalkanoic esters is based on cross-metathesis, dihydroxylation and methanolysis. ... 

Of course, syntheses of annulated aromatic compounds via classic Mizoroki-Heck reaction of aryl (pseudo)halides are prevalent a selection of substrates with open-chain allyl moieties is depicted in Scheme 5.4. Simple aryl iodide 19a was cyclized in high yield (90%), but in a 60 40 mixture of exocyclic and endocyclic double-bond isomers (19a -> 20a) [21]. A structural modification, conjugation with an ester group, a recurrent motif in Mizoroki-Heck chemistry, allowed for preparation of isomerically pure 20b in 74% yield (19b 20b) [22]. In the second example, reaction of pyridine 21 leads to an intermediate... 

Mori, A., Danda, Y., Fujii, T. et al. (2001) Hydroxorhodium complex-catalyzed carbon carbon bond-forming reactions of sUanediols with o ,j8-unsaturated carbonyl compounds. Mizoroki-Heck-type reactions vs conjugate addition. J. Am. Chem. Soc., 123, 10774-5. 

Heck reactions on nonconjugated dienes create an electrophilic Jt-aUyl complex that is susceptible to nucleophilic attack. When the compound contains a conjugated diene, the regioselectivity becomes a very important issue, which must be considered. Cascade sequence involving a Heck reaction and a Jt-allyl reaction could be found in the formal total synthesis of Morphine by Overman [15]. Treatment of dienes with PdCOCOCFjj CPPhj) and NEtj in toluene led to formation of the backbone of Morphine in 56% yield (Scheme 7.6). 

Compounds similar to the above may also be obtained by an intramolecular Heck-type reaction of the bromo compound 103. Treatment of 103 with palladium(ll) acetate gives a mixture of two isomers, of which the major is 104 (with the more extended conjugation) (Equation 20) <1995JOC2312>. 

The consecutive reaction of vinyl halides and alkenes with activated methylene systems [42] in the presence of a palladium catalyst and phase-transfer catalyst results from the addition of the methylene carbanion with the initially formed Heck product (Scheme 6.31) an intramolecular version of the reaction leads to the formation of bicycloalk-l-enes (Scheme 6.31) [42], The analogous combined coupling reaction of iodoarenes and activated methylene compounds with non-conjugated dienes under similar conditions forms the monoalkene (Scheme 6.31) [43]. 

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