Heck general scheme

The mechanism of the Heck reaction (Scheme la) with bidentate phosphine ligands is generally thought to follow the four-step catalytic cycle shown in Scheme lb, with the individual steps being A) oxidative addition of 1 to the Pd°... 

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

A very recent addition to the already powerful spectrum of microwave Heck chemistry has been the development of a general procedure for carrying out oxidative Heck couplings, that is, the palladium)11)-catalyzed carbon-carbon coupling of arylboronic acids with alkenes using copper(II) acetate as a reoxidant [25], In a 2003 publication (Scheme 6.6), Larhed and coworkers utilized lithium acetate as a base and the polar and aprotic N,N-dimethylformamide as solvent. The coupling... 

The twofold Heck arylation of ethylene and ethylene equivalents, initially investigated by Heck himself, provides an easy access to stilbene derivatives 39-Ar (Scheme 14)." The pressure of ethylene has to be carefully controlled, otherwise styrene derivatives, which are initially formed in this process, will be found as major products. In general, a slightly elevated pressure (1-5 bar) of ethylene is favorable for the vicinal twofold coupling leading to stilbenes in up to 69% yield." ... 

Ruhland et al. used both the Suzuki and Heck (see above) reactions on solid support in their generation of libraries of biaryl- and styryl-substituted [3-lactams.45 A preliminary investigation was performed into the most generally suitable catalytic system for preparation of their libraries. This featured coupling of phenylboronic acid with a resin-bound iodophenyl [3-lactam 32 (Scheme 36) the latter compound had been formed from a... 

Recent development of the Heck reaction has also led to greater understanding of its mechanistic details. The general outlines of the mechanism of the Heck reaction have been appreciated since the 1970s and are discussed in numerous reviews [2,3]. More recently, two distinct pathways, termed the neutral and cationic pathways, have been recognized [2c-g,3,7,8,9]. The neutral pathway is followed for unsaturated halide substrates and is outlined in Scheme 8G. 1 for the Heck cyclization of an aryl halide. Thus, oxidative addition of the aryl halide 1.2 to a (bisphosphine)Pd(O) (1.1) catalyst generates intermediate 1.3. Coordination of... 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

For the Heck reaction as discussed in Section III.2.1 the final position of the olefi-nic double bond of the products must not necessarily be the same as in the starting materials (for example Schemes 8, 9, and 10 of Section III.2.1) [1], The selectivity is often driven by stereochemical requirements, because the /1-hydrogen elimination step which forms the double bond proceeds exclusively in a syn manner (if a trans /3-hydrogen is eliminated, one should suspect major deviations from the general mechanism of the Heck reaction, for example electrophilic substitution instead of carbopalladation). An impressive example of a double bond migration is depicted in Scheme 1 - instead of olefins the coupling reaction of iodobenzene 1 with the olefmic alcohol 2 results in the isomeric aldehydes 3 and 4 as final products [2], Reactions of this type have emerged as valuable tools for the synthesis of carbonyl compounds and also as crucial steps in domino processes. 

Despite an earlier failure to achieve cyclic carbopalladation-carbonylative termination in competition with the cyclic Heck reaction [67] (Eq. 3 in Scheme 35), a series of investigations by Aggarwal [117-119] has provided useful solutions to this problem. In cases where the substrates contain a heteroatom group, such as O or NTs, the cyclic Heck reaction can be suppressed [117] (Eq. 1 in Scheme 37). This reaction has been applied to an asymmetric synthesis of avenaciolide [119] (Eq. 2 in Scheme 37). A more general solution to avoiding the cyclic Heck reaction is not to use a base, e.g., Et3N, and promote rehydropalladation to reserve /(-elimination through the... 

The proposed mechanism for a standard Heck reaction is depicted in Scheme 6.5. Generally, a haloalkene or haloarene undergoes oxidative addition to an in situ generated, coordinatively unsaturated 14-electron palladium(O) complex, but other substrates such as tosylates, triflates or diazonium salts can also be applied. Subsequent, sy -insertion into the C=C double bond of a complexed olefin yields a t7-(j -alkenyl) or (j- aryl)alkylpalladium complex. If no hydrogen atom in a pseudo cis-position relative to the palladium is present, an internal rotation step is required prior to syw-elimination of the olefin to afford the traws-olefin product and a palladium(II) hydride complex. The latter is restored to the initial Pd(0) species by base-induced reductive elimination.137"401... 

Mechanism The Heck reaction has become a powerful tool in organic synthesis, but the mechanism of this reaction has remained a topic of debate since the reaction s discovery. The general mechanism for the Heck reaction which is widely accepted is outlined in Scheme 5.4. 

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