Intramolecular Heck coupling reactions

Hudlicky et al. described an elegant strategy based on two intramolecular Heck coupling reactions for the enantioselective synthesis of codeine from 2-phenylbro-moethane (Scheme 10.36).64... 

An intramolecular Heck coupling reaction of aza-MBH products obtained from ort/zo-halobenzaldehydes has been conducted in the presence of the Pd(OAc)2/P(o-tolyl)3 catalytic system with triethylamine, giving con-formationally constrained scalfolds 836 in 45-60% yields (Scheme 2.242). ... 

Scheme 15.11 Suppression of double-bond isomerization in intramolecular Mizoroki-Heck coupling reactions.

Scheme 8.55 Reductive intramolecular Heck-coupling reactions leading to heterocycles [1 78],...

By Intramolecular Heck Coupling. The intramolecular Heck reaction has been used to prepare tetracyclic ethylenic esters required for testing as anti-inflammatory agents (eq 113). ... 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

Intramolecular oxo- or aminopaUadation provides an eflFicient tool for the preparation of various heterocyclic derivatives in recent years. In 2010, Alvarez et al. reported an effcient palladium-catalyzed tandem intramolecular oxopalladation/oxidative Heck coupling reaction toward benzofuians 196 [77] (Scheme 6.54). Nucleophilic attack of the oxygen to the activated carbon-carbon triple bond furnishes vinylpal-ladium intermediate 197, followed by alkene insertion into the C-Pd bond to afford alkylpalladium intermediate 198. The final product was generated via P-hydride elimination of intermediate 198. 

Similarly, the Tietze group has described an intramolecular microwave-promoted Heck reaction for the construction of the B ring in the synthesis of enantiopure B-nor-estradiol analogues (Scheme 6.10 a) [29]. The Heck coupling took place from below, anti to the angular methyl group, to form a single diastereoisomer. The best... 

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. 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

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]. 

Transition metal catalyzed insertion reactions offer a convenient route for the preparation of five membered heterocyclic rings. Besides intramolecular Heck-couplings and CO insertion, examples of the intramolecular insertion of an acetylene derivative constitute the majority of this chapter. Although some of these processes involve the formation of a carbon-heteroatom bond, they are discussed here. 

The reaction of /V-pentenyl-2-iodoindole in the presence of a palladium-triphenylphosphine catalyst led to the formation of a mixture of isomeric products in good yield (4.8.), Addition of thallium(I) acetate favoured the formation of an exocyclic double bond, while in its absence the product containing the endocyclic olefin moiety is formed preferentially. The shortening of the A-alkenyl chain by one carbon leads to the selective formation of a five membered ring.9 Starting from indole-carboxamide derivatives both /3-. and carbolinones are available in intramolecular Heck coupling. 

The participation of halopyrroles in Heck coupling is mostly limited to intramolecular transformations. In a recent example of intermolecular Heck reaction different A-protcctcd 3-iodo-4-trimethylsilyl-pyrroles were coupled... 

Palladium-catalyzed coupling reactions of the Heck type have in many instances involved indole and pyrrole derivatives. Although the mechanisms are complex, organopalladium species are implicated (84H(22)1493). Vinylation of A-substituted-3 -iodoindoles with amidoacrylate groups provides a useful functionalization of indoles (Scheme 81) (90JOM(39l)C23). Yields are improved in intramolecular reactions, e.g. (406 — 407) and (408 — 409) <92H(34)219,91CPB2830). 

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. 

The same group developed an interesting intermolecular palladium-catalyzed alienation of aryliodide with N-tosyl o-iodoanilines with nucleophiles in combination with two palladium-coupling reactions [69]. In this reaction, the N-allyl(2-iodopalladium)aniline intermediate 52 underwent an intramolecular Heck reaction followed by a cross-coupling reaction with phenyl boronic acid to give the 3,3-disubstituted indoline 53 in 78% yield (Scheme 8.27). 

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