Heck-type compound

A drawback of the Heck-type reaction is that it is not strictly regioselective [119]. Depending on the substituents >1% of 1,1-diarylation is observed. Soluble 2,5-dialkoxy-PPVs 63 or 2-phenyl-PPV PPPV 93, without 1,1-diarylated moieties, were synthesized by Heitz et al. in a Suzuki-type cross coupling of substituted 1,4-phenylenediboronic acids and fran5-l,2-dibromoethylene, catalyzed by Pd(0) compounds [120]. However, about 3% of biaryl defect structures are observed in the coupling products (M up to 12,000), resulting from homocoupling of boronic acid functions. 

Diazonium salts react with various nucleophiles in water (Eq. 11.62).106 In acidic aqueous solution, p-pheny I e ncbis di azo ni um ion reacts with alcohols more rapidly than it does with water.107 In the presence of nucelophiles such as halides, the substitution products are obtained. Furthermore, diazonium salts of aromatic compounds are excellent substrates for palladium-catalyzed coupling reactions such as the Heck-type reactions in water. 

Toyota, Ihara and coworkers [178] used a combination of a Wacker- and a Heck-type transformation to construct the cedrane skeleton. Thus, reaction of 6/1-374 using 10mol% Pd(OAc)2 under an atmosphere of 02 led to the domino product 6/1-375 in 30% yield. In addition, 58% of the mono-cyclized compound 6/1-376 was obtained (Scheme 6/1.94). 

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>. 

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

Suitably positioned vinyl halide can undergo Heck-type intramolecular coupling to generate dienes (equations 124 and 125)216,217. When one of the reacting partners in the Heck reaction is a diene, trienes are obtained (equation 126)218. Heck coupling of ally lie alcohols and alkenyl iodides has been employed for the synthesis of vitamin A and related compounds (equation 127)219,220. A similar double Heck reaction on a Cio-diiodide with a Cis-allylic alcohol leads to -carotene as a mixture of isomers (equation 128)209e. 

Heck-type arylation reactions of organobismuth compounds were first reported by Asano et al. in 1973 [11]. This article described the stoichiometric reaction of styrene, Ph3E (E = group 15 elements) and Pd(OAc)2 (Scheme 2). Ph3Bi afforded frans-stilbene only in 7% yield. The major product was biphenyl, which was... 

Scheme 5 Heck-type phenylation reaction with organobismuth compounds...

This section did not appear in CHEC-I(1984) and CHEC-II(1996) <1984CHEC(2)1, 1996CHEC-II(6)1>. Examples are the intramolecular Heck-type reaction of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one and 5-(2-bromophenyl)-2-methyl-6-phenylpyridazin-3(2//)-one which yields 2-benzyldibenzo[/, ]phthalazin-l(2//)-one and 2-methyldibenzo[/,. ]cinnolin-3(270-one, respectively <2003T5919>. The same compounds were also obtained from the corresponding 2-aminophenyl (instead of 2-bromophenyl) derivatives via diazotization and subsequent Pschorr reaction. 

The counter-ions of some of the quaternary onium groups were exchanged with an anionic phosphine compound, which was then used to complex palladium. Thus, a polymer material containing phase transfer catalyst and transition-metal catalyst groups was obtained (Fig. 20). The Heck-type vinyla-tion reaction [137] was used to examine the catalytic activity of the heterogeneous system. The polymer-supported catalyst was found to compare favourably with the homogeneous system (Fig. 21). 

The primary product of the Heck type ring closure is an indole derivative containing an exocyclic double bond. This compound, however in most cases isomerises spontaneously to the aromatic isomer. In the example shown in 3.9. the addition of silver carbonate prevented the isomerisation of the double bond into the five membered ring.12... 

A search of the literature revealed a 1982 Trost and Fortunak paper [58] wherein PdCL and AgBF4 were utilized to effect the Heck-type cyclialkylations of various isoquinuclidine model compounds. Compound 100 was exposed to these conditions, affording the heptacycle 101 in 63-82% yields. 

The formation of compound 175 could be rationalized in terms of an unprecedented domino allene amidation/intramolecular Heck-type reaction. Compound 176 must be the nonisolable intermediate. A likely mechanism for 176 should involve a (ji-allyl)palladium intermediate. The allene-palladium complex 177 is formed initially and suffers a nucleophilic attack by the bromide to produce a cr-allylpalladium intermediate, which rapidly equilibrates to the corresponding (ji-allyl)palladium intermediate 178. Then, an intramolecular amidation reaction on the (ji-allyl)palladium complex must account for intermediate 176 formation. Compound 176 evolves to tricycle 175 via a Heck-type-coupling reaction. The alkenylpalladium intermediate 179, generated in the 7-exo-dig cyclization of bro-moenyne 176, was trapped by the bromide anion to yield the fused tricycle 175 (Scheme 62). Thus, the same catalytic system is able to promote two different, but sequential catalytic cycles. 

Alkenyliodonium salts can be used as highly reactive substrates for Heck-type olefination and similar palladium-catalyzed cross-coupling reactions [63 -65]. In a recent example, a series of dienes 80 were stereo- and regioselectively prepared by a palladium-catalyzed Heck-type reaction of alkenyliodonium salts 79 with a,/3-unsaturated carbonyl compounds (Scheme 37) [64]. 

Similar to alkenyliodonium salts (see Sect. 6.3), aryliodonium salts are highly reactive substrates in Heck-type olefination and other palladium-catalyzed coupling reactions. Aryliodonium salts can serve as very efficient reagents in the palladium-catalyzed arylations of acrylic acid 101 [75], organotin compounds 102 [76], sodium tetraphenylborate 103 [77], and copper acetylide 104 [78] (Scheme 45). 

A rhodium(l)-catalyzed system in THF is also effective in the Mizoroki-Heck-type reaction of arylsilanediols with acrylates (Scheme 4).53 Interestingly, the use of aqueous THF switches the reaction to 1,4-addition forming /3-arylated esters. The proposed catalytic cycles for these reactions involve 1,4-addition of an arylrhodium species to an acrylate. The change of the reaction pathway is probably because, in aqueous THF, the resultant Rh enolate 6 undergoes protonolysis rather than /3-elimination. Similar Rh-catalyzed 1,4-additions to a,/3-unsaturated carbonyl compounds have been achieved with arylsilicones,54 arylchlorosilanes,55 and aryltrialkoxysilanes.56,57 The use of a cationic Rh-binap complex leads to highly enantioselective 1,4-additions of alkenyl- and arylsilanes.58 583... 

Because many 4-benzylpiperidines are physiologically and pharmacologically active, an efficient route to these compounds was developed <03TL8249>. Cyclization of imines containing an allylsilane with aldehydes in a one-pot reaction resulted in 4-methylenepiperidines in good yields. Heck-type arylation of arylboronic acids with 4-methylenepiperidines afforded the styryl derivatives, which gave the desired piperidines on reduction. 

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]. 

Drastic changes in regioselectivities were observed when intramolecular Heck-type cyclization was performed in an aqueous medium using Pd (OAc)2/tppts as the catalyst the selective formation of the e do-cyclized compound was observed instead of the exo compound obtained in a usual organic medium [Eq. (16)] [105]. 

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