Heck reaction stereochemistry

Pd complexes 9-12 were tested for their catalytic behavior in the asymmetric Heck reaction involving the phenylation of 2,3-dihydrofuran (Scheme 3). The results are summarized in Table 2. The two isomeric products of 2-phenyl-2,5-dihydrofuran are formed with varying yields from 80% to 0%. The obtained ee s are high. Complex 12 is shown to be catalytically inactive. The lack of catalysis in complex 12 is rationalized by differences in the steric requirements between the diphenylphosphinites 1-3 (cone angle >140°) and the more sterically hindered cyclohexyl-phosphinite 4 (cone angle >170°) and the resulting stereochemistry on the Pd center. The ligands in complex 12 adopt a... 

Heck reactions, the hydroarylation methodology, has been a key tool in the synthesis of varions epibatidine analogues, due to the ability of this approach to address regio- and stereochemistry in substituted azabicyclo ring systems [6],... 

It has been proven that palladium catalyzed reductive Heck reactions are versatile and high-yield approach for preparing of new bioactive alkaloid epibatidine (1) analognes fromN-benzoylated 2-aza-bicyclo[2.2.1]hept-5-ene (3) and it has been shown that in case of aryl- groups reaction progresses regioselectively. All Heck type reactions proceed exo-selectively, leading to the same stereochemistry as fonnd in 1. 

Vinylation of vinyl halides (cf., 12, 368). The original phase transfer catalyzed version of this Heck reaction suffers from partial loss of the stereochemistry... 

In a series of studies, Shibasaki examined the formation of chiral benzylic quaternary centers by using asymmetric intramolecular Heck reactions. The effect of double-bond stereochemistry was examined in the cyclization of aryl Inflates 9.1 and 9.3 (Scheme 8G.9) [22], As is commonly... 

Intramolecular versions of the Heck reaction are very useful for the construction of ring systems. The entropic advantage of having both coupling partners present in the same molecule increases the efficiency of the insertion reaction and leads to efficient reactions. Moreover the intramolecular version can be carried out on hindered substituted alkenes, whereas the intermolecular Heck reaction is largely restricted to monosubstituted alkenes. These reactions illustrate the syn stereochemistry of both the insertion reaction and the elimination. A number of multicyclic natural products have been synthesized using intramolecular Heck reactions to assemble the skeletons, and this has become a powerful synthetic tool for such compounds. 

Controlling the coordination of palladium intermediates with silver salts was the key to developing highly diastereo- and enantioselective Heck reactions.58 For example, the presence of silver phosphate in the key cyclization step during the synthesis of various alkaloids reversed the stereochemistry at the newly created spiro center (Scheme 10.33).59... 

The Heck reaction is the palladium-catalyzed coupling of an aryl or vinyl halide with an alkene to give a new C—C bond at the less substituted end of the alkene, usually with trans stereochemistry. 

As p-hydride elimination is reversible, hydropalladation with the opposite regiochemistry provides a mechanism for forming regioisomers of the alkene. This allows the most stable alkene that is accessible by the hydropalladation-dehydropalladation sequence to dominate. The only restriction is that all of these processes are syn. The migration can be prevented by the addition of bases like silver carbonate, which effectively removes the hydrogen halide from the palladium complex as soon as it is formed. This synthesis of a complex trans dihydrofuran involves the Heck reaction followed by alkene isomerization and then a Heck reaction without migration to preserve the stereochemistry. 

Retention of stereochemistry is demonstrated by the reaction of a substituted malonate with epoxycyclopentadiene. Palladium adds to the side opposite the epoxide so the nucleophile is forced to add from the same side as the OH group. This, no doubt, helps 1,4-regioselectivity. The required pal-ladium(O) phosphine complex was formed from a palladium(II) complex as in the Heck reaction. 

Revision of allyl silane chemistry (pp. 1296-300) and the stereochemistry and mechanism of ar intramolecular Heck reaction. 

The second Heck reaction of 102 (E/Z isomers) utilizing the vinyl bromide function, which had been employed in the synthesis of codeine by Trost (see Sect. 2.2.1), afforded phenanthrofuran skeleton 103 in 44% yield (Scheme 20). Since only the Z-isomer of 102 can participate in the cyclization reaction, this Heck cyclization resulted in the rather modest yield. After deprotection of the 0-TBS group in 103, the stereochemistry at C-6 hydroxy group was inverted by... 

The stereochemistry associated with the Heck reaction is consistent with what we now expect with a process involving 1,2-insertion and -elimination—syn addition to the olefin and syn elimination to form a new alkene. When monosubstituted... 

Rapid development in the Heck reaction has made it one of the most important of all modem methods. A dramatic example is a recent synthesis of strychnine by M. Nakanishi and M. Mori.23 This synthesis illustrates the intramolecular Heck reaction particularly well, showing examples of regioselectivity in attack on the alkene and in formation of the new alkene. The synthesis starts with a Heck reaction on enantiomerically pure 149. Attack occurs on the nearer end of the alkene to give 150 that cannot eliminate to reform the same alkene as there are no H atoms left and the alkene 151 must be formed. The stereochemistry is controlled by the short tether linking the aryl bromide and the alkene. 

Intramolecular Mizoroki-Heck reactions with styrene-type alkenes constitute the second frequently met case. Finding suitable rationales in theses cases seems to be more intricate. There is some evidence for a mechanism involving a radical intermediate [11]. Most explanations, however, cite a facile epimerization at the benzylic position and, thus, furnishing the required cw-stereochemistry or a base-assisted reductive elimination of the palladium species (Scheme 6.3) [11]. In some cases, suitable substrates or conditions can lead to the a r/-elimination products via an Elcb-type mechanism [23,24]. 

The ultimate step in the total synthesis of ( )-dehydrotubifoline (157), a Strychnos alkaloid, is an intramolecular Mizoroki-Heck reaction of H-like (Figure 6.4) substrate 156 (Scheme 6.45) [115]. This ring closure preserved the integrity of the double-bond stereochemistry and delivered, after the excepted enamine-imine tautomerization, the desired product 157 in excellent yield. 

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