Heck reaction, with dienes

The Heck reaction with 1,3-dienes can lead to in situ generation of allyl-Pd complexes, with nucleophile coupling in a second step (equation 63). 

The intermediate 591a was also used in a synthesis of tabersonine. Alkylation of 591a by Z-l,3-di-iodopropene followed by elimination of the phenylselenyl group gave a ring C diene 594, which was cyclized by a reductive Heck reaction with palladium acetate, sodium formate, triphenyl-phosphine, and base, with formation of tabersonine (78) in 43% yield (Scheme 77) (346). 

Scope and limitations of the Heck reaction synthesis of dienes The Heck reaction with electron-rich alkenes A synthesis of strychnine Recent developments in the Heck reaction Sp2-sp2 Cross-Coupling Reactions by Transmetallation Stille coupling... 

A facile synthesis of 2-aryl-1,3-dienes has been realized from aryl halides and allenes. Ionic liquids prove to be a superior media for the Heck reaction with aryl... 

Double Heck reactions of vicinal ci5 -l,2-dihaloalkenes provide an easy access to (E,Z,E)-1,3.5-hexatrienes, which are valuable building blocks for organic synthesis. t t The first example of a twofold double, that is, essentially a fourfold, Heck reaction with a bis(dibromo)cycloalkene has been conducted on the strained l,2,9,10-tetrabromo[2.2] paia-cyclophane-1,9-diene, which is available in multigram quantities. The Heck reaction proceeded cleanly under phase transfer conditions, as developed by Jeffery, f i to give the tetraalkenylated products in moderate to good yields (Table 8). The resulting bishexatrienes... 

In 2003, Hu et al. developed a novel palladium-catalyzed Heck reaction of dienes with benzyl halides to generate dihydropyrroles [7a] (Schane 6.1). A series of benzylic halides were employed snccessfully, although electron-withdrawing snbstituents led to... 

The Heck reaction of alkenyl halides with olefins provides a short access to dienes that in turn can undergo Diels-Alder reaction with added dienophiles. This reaction can be conducted in an intramolecular fashion to provide annelated cyclohexene derivatives. Ang et al. systematic investigated the intramolecular Heck reaction with 2-bromo-1,6-dienes that in turn cycloadd external dienophiles (Scheme 5-209). " ... 

Microwave-assisted Heck reactions have also been carried out with triflates as coupling partners, involving some very complex molecules. Winterfeld and coworkers have reported a multigram synthesis of a complex non-symmetrical bis-steroidal diene by microwave-promoted coupling of the corresponding alkene and triflate steroidal moieties (Scheme 6.8) [27]. 

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. 

An interesting approach to the pyrrolizidine skeleton was devised wherein pyrrole-2-carboxaldehyde (70) underwent A-allylation under basic conditions and subsequent olefmation with ethyl p-tolylsulfinylmethanephosphonate to produce the pyrrolyl alkene 71 <00TL1983>. Intramolecular Heck reaction of the iodo species then produced the 1 -p-tolylsulfinyl-1,3-diene 72. 

Heck reactions have also been used by Helmchen et al. for a two-component domino process of a,co-amino-1,3-dienes.1721 By using palladium complexes with chiral phosphino-oxazolines as catalysts an enantiomeric excess of up to 80 % is achieved. In a... 

The Heck reaction on polymer-bound iodoarenes is assisted by the addition of a catalytic amount of tetra-n-butylammonium bromide and has been employed in the synthesis of 4-carboxycinnamic esters and amides [33], and 4-aminosulphonyl-cinnamic esters [34], It has also been reported that the presence of an equimolar equivalent of benzyltriethylammonium chloride aids the Pd(II)-mediated reaction of A -acyl-2-iodoanilines with vinylidene carbonate, which leads to A -acyl-2-hydroxy-indolines providing a convenient route to the indoles (80-90%) [35], The catalysed reaction of 2-hydroxy- and 2-tosylaminoiodobenzene with 1,2-dienes produces 1,2-dihydrobenzofurans and 1,2-dihydroindoles, respectively [36]. 

In the cyclization of the (iodoaryl)diene, N-methyl-N-(l,5-hexadiene-3-yl)-2-iodobenzoic acid amide, the combined yield of the tricyclic products arising from a double intramolecular Heck reaction reached 52 % when the catalyst was prepared from [Pd(OAc)2] and 1,10-phenanthroline and the reaction was run in ethanol/water 1/1 (Scheme 6.4) [18,19]. Interestingly, in CH3CN the reaction did not proceed at all with this catalyst. It is also noteworthy, that Pd-phenanthroHne complexes are rarely used as catalysts in Heck-type reactions. 

Coupling of 1 with iodobenzene under Heck reaction conditions gave the phenyl-substituted diene 242-Ph which was isolated in up to 78% yield [146-148]. When heated at 80 °C in DMF or MeCN with various dienophiles 244-R (acrylate, maleate, or fumarate), 242-Ph and its analogs 242-Ar obtained from 1 and other haloarenes cleanly gave the spiro[2.5]octene derivatives 245-Ar (Scheme 57). 

Methyl 2-bromo-2-cyclopropylideneacetate (11a) has never been tested in these reactions, but has been used as a starting material for the stepwise construction of 1,6-heptadienes with methylenecyclopropane units for intramolecular Heck reactions. Thus, bromo ester 11a, after reduction, subsequent conversion of the resulting alcohol to the bromide and coupling with enolates of substituted malonates, was transformed into dienes of the type 254 (Scheme 73) - versatile synthetic blocks for the preparation of functionally substituted spirocyclopropanated bicyclo[4.3.0]nonenes 255a-d by a domino Heck-Diels-Alder reaction [122a]. 

Polystyrene-bound secondary aliphatic amines and /V-alkyl amino acids can be ally-lated by treatment with a diene and an aryl iodide or bromide in the presence of palla-dium(II) acetate (Entry 14, Table 10.3). As the diene, 1,3-, 1,4-, and 1,5-dienes can be used, and, besides aryl halides, heteroaryl bromides have also been successfully used [63], This remarkable reaction is likely to proceed via the formation of an aryl palladium complex, with subsequent insertion of an alkene into the C-Pd bond. The resulting organopalladium compound does not undergo ( -elimination (as in the Heck reaction), but isomerizes to an allyl palladium complex, which reacts with the amine to give the observed allyl amines. 

Benzofurans and dihydrobenzofurans have been prepared on polymeric supports by the palladium-mediated reaction of 2-iodophenols with dienes or alkynes (Entries 1 and 2, Table 15.9). This reaction is closely related to the synthesis of indoles from 2-iodoanilines, and probably proceeds via an intermediate palladacycle (Figure 15.3). Benzofuran and isobenzofuran derivatives have also been prepared on cross-linked polystyrene by intramolecular addition of aryl radicals to C=C double bonds and by intramolecular Heck reaction. 

In their pioneering work on the catalytic carbopalladation reaction of 1,2-heptadiene with phenyl iodide in the presence of a suitable base, Shimizu and Tsuji observed the formation of the corresponding substituted 1,3-dienes 62 via a / -hydride elimination from the 7z>allyl intermediate 61 [61]. Based on these observations, a three-component Heck-Diels-Alder cascade process has been developed by Grigg and co-workers [73]. A wide variety of aryl and heteroaryl iodides were used for the intermolecular reaction with dimethylallene to afford the corresponding 1,3-dienes. These subsequently react in situ with N-methylmaleimide to give the bicyclic adducts 63 (Scheme 8.30). 

The differentiation of enantiotopic C=C double bonds in the intramolecular Heck reaction of 1,3-diene 116 using (S)-BINAP, and subsequent regioselective carbanion capture of the 7i-allylpalladium intermediate 117 gave 118 with 87% ee with complete diastereo- and regioselectivity. A, ll2)-Capncllene (119) was synthesized from 118... 

The Shibasaki cychzation of mc.vo-cyclohexa-1,4-dienes in the presence of a chiral palladium complex and silver carbonate in l-methyl-2-pyrrolidinone is probably the first example of an enantioselective Heck reaction (Scheme 10.34).60 The enantiomeric excess could be slightly improved by replacing the chiral phosphine ligand BINAP with the corresponding less coordinating arsine ligand, as well as replacing silver carbonate with silver phosphate.61,62... 

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