Vinyl halides natural products synthesis

Organozinc reagents have been coupled with halides in the synthesis of dienes and other conjugated systems to form new carbon-carbon bonds such reactions have been reviewed477-479. In particular, the reaction of alkynyl zinc reagents with vinyl halides has been used in natural product synthesis, usually catalyzed by palladium complex catalysts. 

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

An optimum enantioselectivity of 90% and yield of 72% was observed for the aUyl bromide/benzaldehyde system at 5°C. In contrast to ligand 11, this new salen ligand 14 was also able to affect an enantioselective addition of aUyl iodide. Related (3-methallyl halides reacted as smoothly as the allyl halides although the enantioselectivities were lower. To demonstrate the applicability of this methodology to polyketide natural-product synthesis, p-methoxybenzyl (PMB)-protected 3-hydroxypropanal was coupled with aUyl bromide in an excellent enantioselectivity of 92%, albeit in a moderate yield of 69%. Finally, vinyl iodides and triflates were used as substrates, with 2 mol% of Ni(II) required for efficient coupling. The addition of fi-l-iodohex-l-ene to PMB-protected 3-hydroxypropanal afforded the corresponding S-allylic alcohol adduct in 75% ee. A vinyl triflate also... 

A. number of rutro compounds used m ndturdl product synthesis have been prepared by the n of alkyl halides Some recent examples are summarized m Table 2 4 fi-Nitro carbonyl compounds are important for synthesis of natural products The reaction of alkyl vinyl ketones with sodium nitrite and acetic acid in THF gives thecorrespondmgfi-nitro carbonyl compounds in42-82% ""rhis method is better for the preparation of fi-nitro carbonyl compounds than the nitration of the corresponclmg halides... 

Parco et al. described a copper-catalyzed amidation of vinyl iodide 115 to give 116 (Scheme 20).28e Enhanced conversions were attained using copper(i) thiophenecarboxylate (GuTG) in a polar aprotic solvent such as NMP. The total synthesis of the antitumor natural product, lobatamide G, has been accomplished by using this reaction.28f Buchwald et al. developed a general and efficient copper-catalyzed method using N,N -dimethyl ethylenediamine L8. The double-bond geometry of the alkenyl halides was retained under the reaction conditions. 

If the halide and the hydroxy group are present in the same molecule, reaction (107) leads to the synthesis of lactones.484 With complex (102) as catalyst a series of butenolides were prepared in good yields from vinyl iodides (equation 110). Four- and six-membered ring lactones and a-methylene lactones were prepared. 5,486 The mechanism proposed was analogous to that of Scheme 37. This cyclization has been used in the synthesis of the natural product zearalenone.487 PdCl2 was the catalyst. 

Although the coupling of aiyl halides with alkenes (commonly referred to as the Heck reaction) was first reported more than 25 years ago [ 1 ], only in the past decade has its enormous synthetic potential been realized [2], Within that time, the reaction has been extended to many substrates, including vinyl iodides and bromides and enol triflates. Moreover, the intramolecular variant has become one of the more important reactions for the formation of carbon-carbon bonds and has emerged as a premier method for the construction of quaternary carbon centers. The ability of intramolecular Heck reactions to reliably fashion carbon-carbon bonds in polyfunctional molecules has led to wide application of this reaction at the strategy level for the synthesis of complex natural products [2g],... 

New reports of organozirconium-organic halide cross-coupling reactions have almost completely stopped. Nevertheless, the palladium-catalyzed cross-coupling of vinyl zir-conocenes (from alkyne hydrozirconation) with vinyl halides has been employed in the synthesis of the lipid isobutylamide natural product anacyclin (equation 98). ... 

There are several cases of applications of vinylboron-vinyl halide coupling reactions in synthesis of targeted natural products or related molecules225,233,234 the synthesis of (5 S,6i )-5,6-DiHETE methyl ester (where DiHETE = Dihydroxy-7,9,11,14-eicosatetra-enoic acid) is based on such a reaction for the formation of its trienic portion (equation 122)233. 

Diorganocuprates couple readily with vinylic halides and have been employed in the synthesis of some natural products, e.g., fulvoplumieren and Cecropia juvenile hormone (26, 27, 62, 63). Copper-halogen exchange can occur simultaneously 174, 309). Successful coupling reactions of organocopper compounds with vinylic halides are listed in Table VIII. 

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... 

Vinyl halide is a useful synthetic intermediate for natural products. Knapp et al. reported the synthesis of griseolic acid B (130) via intramolecular radical cychzation of vinyl iodide [40]. Aldehyde 125 was reacted with hydrazine to give hydrazone 126, which was further... 

Mizoroki and Heck first reported their independent discoveries of palladium(0)-catalysed vinylations of aryl halides over 30 years ago [1], This transformation, now known as the Mizoroki-Heck reaction, can be broadly defined as the palladium(0)-mediated coupling of an aryl or vinyl halide (or triflate) with an alkene. The potential utility of this transformation in complex molecule synthesis was largely unappreciated for a number of years however, its application for the construction of complex organic molecules, including natural products, has flourished recently [2],... 

Now Pd-catalyzed carbonylation was used as one carbon elongation method and it has been used for the synthesis of biologically active substances and natural products. In this section, Pd-catalyzed carbonylation of aryl, vinyl, and benzyl halides and pseudo aryl or vinyl halides is described. 

---