Palladium-catalyzed cross-coupling stereospecific

The stereospecific insertion of 2-monosubstituted alkenyl carbenoids was successfully employed in the preparation of 1-alkyl-1-zircono-dienes. The Z and E carbenoids of 1-chloro-l-lithio-l,3-butadiene (69 and 70, respectively) are generated in situ fromE- andZ-l,4-dichloro-2-butene [53] (Scheme 25). Inversion of configuration at the carbenoid carbon during the 1,2-metalate rearrangement stereospecifically yields terminal dienyl zirconocenes 71 and 72 [54] (Scheme 25). As the carbenoid-derived double bond is formed in 9 1=Z E for 69 and >20 1=E Z isomeric mixtures for 70, the metalated dienes 71 and 72 are expected to be formed with the same isomeric ratio. Carbon-carbon bond formation was achieved by palladium-catalyzed cross-coupling with allyl or vinyl halides to give the functionalized products with >95 5 stereopurity [55-57]. 

Like hydroalumination and hydrozirconation, hydroboration of alkynes also provides a convenient and Stereospecific route to alkenyl metal reagents. However, initial attempts to achieve palladium-catalyzed cross-coupling of alkenylboranes with alkenyl halides were unsuccessful, due to the poor carbanionic character of these reagents. Later, Suzuki discovered that the desired transformation could be effected in the presence of an alkoxide or hydroxide base weaker bases, such as sodium acetate or triethylamine, were not generally effective. The reaction is suitable for the preparation of ( , )-, ( ,Z)- and (Z,Z)-dienes. Since reactions of alkenylboronates are higher yielding than those of alkenylboranes, the recent availability of (Z)-l-alkenylboronates " substantially improves the Suzuki method for the preparation of (Z)-alkenes. An extension of the methodology to the synthesis of trisubstituted alkenes has also been reported. " ... 

Dienes and 1 -enynes. Negishi et al.9 have extended the synthesis of 1,3-enynes by palladium-catalyzed cross-coupling of alkynylzinc chlorides with an alkenyl halide (8, 472) to a similar stereospecific synthesis of 1,5-dienes or 1,5-enynes by coupling an alkenyl halide with a homoallyl- or homopropargylzinc chloride. An example is the synthesis of the 1,5-enync I (equation I). This reaction... 

In 1993, Corriu et al. studied the synthesis of nitrogen-containing heterocycles from (Z)-3-(tribulylstannyl)allylamine, which was prepared by the reaction of Af-(trimethylsilyl)allylamine with 2 mol of ra-butyllithium followed by treatment with chlorotributyltin and subsequent hydrolysis. The unprotected (Z)-3-(tributylstannyl)allylamine underwent a palladium-catalyzed cross-coupling reaction with aromatic bromides affording a stereospecific preparation of substituted allylic amines with Z configuration of the carbon-carbon double bond. The reactions of o/t/zo-functionalized aryl bromides offer a one-step preparation of 7-membered nitrogen heterocycles in high yields (Scheme 4.18). 

In recent years, cross-coupling methodology has emerged as a viable tool for enamide synthesis, and, indeed, there are a number of published protocols which employ palladium- or copper-catalyzed stereospecific amidations of vinyl halides [17]. For example, Buchwald and coworkers had recently shown that a copper-catalyzed cross-coupling of vinyl bromides or iodides proceeded with retention of stereochemistry (Scheme 9.16), though the only example using a tetrasubstituted vinyl halide, 23, lacked the need for any stereochemical control in the halide portion [18]. Based on this it seemed feasible that the desired enamide 22 could potentially be assembled via a comparable coupling between amide 24 and a stere-odefined vinyl halide such as 25. 

Baba, S., Negishi, E. A novel stereospecific alkenyl-alkenyl cross-coupling by a palladium- or nickel-catalyzed reaction of alkenylalanes with alkenyl halides. J. Am. Chem. Soc. 1976, 98, 6729-6731. 

Miyaura, N., Yamada, K., Suzuki, A. A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides. Tetrahedron Lett. 1979, 3437-3440. 

Several independent protocols using a combination of transition metal-catalyzed stereoselective hydrosilylation, such as palladium-catalyzed crosscoupling sequence leading to stereodefined r-conjugated alkene derivatives, have been successfully developed in the last decade (4). Alkenylsilanes or siloxanes, prepared via platinum or rhodium complex-catalyzed intermolecular hydrosilylation of terminal alkynes have been highly stereospecifically cross-coupled with aryl and alkenyl halides to give unsymmetrical stilbenes, alkenylbenzenes, and conjugated dienes (Scheme 24) (4). 

Homoallylic alcohol 9 is readily prepared by palladium-catalyzed directed cyanoboration followed by Suzuki-Miyaura cross-coupling (Scheme 5.15) [15]. Palladium-catalyzed allyl transfer from 9 to aryl bromide results in removal of the hydroxymethyl directing group and concomitant formation of 3,4-diaryl-2-butenenitrile albeit the lack of regio- and stereospecificity. The overall transformation proposes a concept of intramolecular reaction with a carbon tether removable through retro-allylation. 

Both the Michaelis-Arbuzov and the Michaelis-Becker reactions are often stereospecific, when compounds containing a chiral phosphorus center are used (retention of configuration), but this property has not been exploited in the synthesis of natural products or their analogs. This is probably a result of often harsh reaction conditions that make them incompatible with the synthesis of more complex, P-chiral molecules. Recently, however, a palladium-catalyzed version of the Michaelis-Becker reaction (a cross-coupling... 

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