Vinyl chemoselective carbonylation

The macrosphelides were isolated in the mid-1990s and found to inhibit cell-adhesion [35], bringing these natural products into the chemical biology spotlight Takahashi and coworkers reported a combinatorial synthesis of 122 macrosphelides, including the natural ones based on two palladium-catalyzed chemoselective carbonylations of vinyl halide, first in an intermolecular fashion and then in a... 

A convenient synthesis of 3-spiro-fused benzofuran-2(3//)-ones was reported via Pd-catalyzed chemoselective carbonylation of vinyl triflates in the presence of o-iodophe-nols, followed by a regioselective intramolecular Heck reaction (Scheme 20). ... 

Chemoselective carbonylation of a vinyl iodide 34 with alcohol containing a vinyl bromide moiety 35 has been successfully employed for the solid-phase synthesis of a macrosphelide precursor 36 [43]. After the 4-methoxyphenylmethyl (MPM) group was removed, the palladium-catalyzed carbonylative macrolactonization of the vinyl bromide 37 achieved the synthesis of the macrosphelide-supported derivative 38 (Scheme 9.13). The combinatorial synthesis of a 122-member macrosphelide library has been performed by the three-component strategy based on the palladium-catalyzed chemoselective carbonylation/macrolactonization reaction. 

The carbonyl ir-bond has been found to add chemo- and regio-selectively across the alkenic ir-bond of ketenes. Thus diphenylketene readily reacts with benzoquinone to yield a stable [2 + 2] adduct (equation 1). With an excess of diphenylketene the bis-adduct is formed, which decomposes into tetraphe-nylquinodimethane and carbon dioxide (equation 2). With the less stable ketene, thermal [2 + 2] cycloadditions are observed with highly electrophilic carbonyl compounds (equation 3). With unactivated aldehydes and ketones, yields are much lower due to a faster oligomerization of the ketene reagent. However, in the presence of a Lewis acid catalyst, most aldehydes or ketones form P-lactones with ketene (equation 4). Cycloadditions with ketones usually require more active catalysts than with aldehydes. The catalyzed reaction of ketene with methyl vinyl ketone is chemoselective, yielding a 10 1 ratio of [2 + 2] versus [4 + 2] adducts (equation 5). In the absence of catalyst, methyl vinyl ketone reacts with ketene to give exclusively the [4 + 2] adduct. 

Johnson and coworkers used hydride, acetylide, or vinyl anion nucleophiles and aldehyde or Michael acceptor electrophiles. It is notable that nucleophilic attack by acetylide ion takes place chemoselectively at the acylsilane carbonyl over the aldehyde carbonyl, likely due to a kinetic preference (Scheme 6.23T... 

Later, in 1991, Suzuki and colleagues developed another methodology for the carbonylative coupling of vinyl halides with organoboranes using Pd(PPh3)4 and K3PO4 as a base [10] to synthesize vinyl ketones in moderate to excellent yields (Scheme 4.3). However, the chemoselectivity dropped and a mixture of... 

Cross-Coupling Reactions. TASF(Et) activates vinyl-, alkynyl-, and allylsilanes in the Pd-mediated cross-coupling with vinyl and aryl iodides and bromides. As illustrated in eqs 8-10, the reaction is stereospecific and chemoselective. This crosscoupling protocol is remarkably tolerant towards a variety of other functional groups such as carbonyl, amino, hydroxy, and nitro. Vinylsilanes can be synthesized from hexamethyldisilane and vinyl iodides in the presence of TASF(Et) (eq 10) via cleavage of a Si-Si bond. Aryl iodides can also be synthesized by this method. TASF is superior to tetra-n-butylanunonium fluoride for these reactions. In the absence of a vinylsilane reagent, one of the methyl groups from the difluorotrimethylsilicate is substituted for the halide (eq 11). ... 

Chiral 2-amino-1,3-dienes with (5)-2-methoxymethyl pyrrolidine substituents react with vinyl carbene complexes, [(OC)5W=C(OMe)C(R3)=C(R )(R5)] to give the cyclohexyl tungsten carbene complexes S6. 27 Cyclic carbenes 57 (R = H, Br, OMe) and 58 are rather unreactive towards 1,3-dipoles and 1,3-dienes and their reactions with diazomethane are regio- but not chemoselective. s The tungsten atom of 59 has distorted octahedral coordination defined by one carbene and five carbonyl ligands. ... 

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