Zinc reagents with aryls

In 2010, Jackson and co-workers studied the Negishi cross-coupling of iodoalanine-derived zinc reagents with aryl iodides and aryl bromides/ In that work, they showed that a 3,4-dihydro-2( H)-quinolinone derivative can be produced by using 2-iodoaniline as a substrate. An interesting study on... 

Terminal and internal arylalkynes have been synthesized by the palladium-catalysed reaction of alkynyl-zinc reagents with aryl halides [equation (14)]. ... 

Two examples for nickel-catalyzed cross-coupling reactions of triflales and mesylates with the requisite zinc and boron species are outlined in Scheme 12.26. In 1994, Snieckus reported the Ni(0)-catalyzed reaction of aryl zinc reagents with aryl triflates and obtained the desired biaryl compounds in... 

The Negishi biaryl coupling, i.e., the reaction of aryl zinc reagents with aryl halides proceeds very smoothly, even with sterically hindered reagents (Scheme... 

With the development of the cross coupling methodology, many 6-C-substituted purines have been prepared in the past decade. Thus, 6 halopurine derivatives react with arylmagnesium halides,25 alkyl(aryl)zinc or tin reagents,26 trialkylaluminum,27 or alkylcuprates28 to give the 6-alkylpurine derivatives. Also a reverse approach based on the reaction of purine-6-zinc iodide with aryl or vinyl halides has recently been described.29 For the synthesis of 6-arylpurines, an alternative approach makes use of radical photochemical reactions of adenine derivatives with aromatic compounds,30 but this method is very unselective and for substituted benzenes, mixtures of ortho-, meta-, and para substituted derivatives were obtained. 

The reactions of a range of aryl, benzylic, and heterocyclic zinc reagents with iodo- and bromoarenes were reported at ambient temperature under biphasic conditions with [C4mmim][PF6] and toluene. The biaryl products were readily isolated by decanting the toluene phase, with yields of 70-92% achieved after several minutes. However, attempts to recycle the catalytic ionic liquid solution resulted in significantly decreased activities. 

Biphenyls. The cross-coupling of arylzinc chloride reagents with aryl triflates constitutes a convenient method for assembling biphenyls. The zinc reagents are accessible from directed o-metallation and metal-metal exchange. 

Several AT-protecting groups were explored with indol-2-ylzinc reagents and the best results in cross-coupling with iodobenzene were obtained with the 1-Boc-derivative <93H(36)941>. Both 2-iodo and 3-iodo-l-phenylsulfonylindole have been converted directly to zinc reagents with active zinc and then coupled with aryl halides <93TL5955>. 

Palladium-catalyzed polycondensation of zinc organometaUic reagents with aryl bromides... 

The Buchwald lab has also demonstrated that allylic zinc halides afford site-selective coupling with CPhos ligands as shown in Scheme 16.3. Cross-coupling of 3,3-disubstituted allylzinc reagents with aryl halides has been difficult due to regiochemical issues often observed with this class of nucleophile. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Alkynil zinc reagents have also been employed to afford coupling reactions with phenyl-bntyl tellnride and aryl iodides. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

The sequential approach is also common in proposals written by synthetic chemists (a multistep synthesis is inherently step by step). Vyvyan (excerpt 13N), for example, proposes a strategy to synthesize a select group of heliannuols (alleo-pathic natural products isolated from the sunflower) in an optically pure form. One approach that he will explore involves enantioselective cross-coupling reactions between an alkyl zinc reagent and an aryl bromide. He begins with experiments that will utilize recently developed catalysts and produce products with known optical rotation data. Subsequent reactions are described that will lead potentially to the desired stereospecific heliannuols A and D. 

Once this process is explored with the model system to assess the level of enantioselectivity, we will then prepare alkyl zinc reagent 48 from 44 using standard methods - - and cross couple 48 to aryl bromide 18 using the appropriate chiral catalysts (Scheme 7). Although the acetonide stereocenter in 48 is somewhat remote from the coupling site, the stereocenter may serve to enhance the stereoselectivity of the cross-coupling process because the two possible products are diastereomers, not simply enantiomers. This reaction will produce 49 from (S)-48 and 30 from (R)-48 that can then be converted to epoxides 31 and 32 using standard methods. Epoxide 31 leads to heliannuol D 4 after base-promoted epoxide cyclization and deprotonation. Similarly, epoxide 32 leads to heliannuol A 1 after acid-promoted cyclization. 

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