Natural products aryl-alkenyl coupling

Some detailed aspects of the syntheses of the following compounds are presented in Sect. III.2.6. The scheme numbers indicated in parentheses are those in Sect in.2.6 methyl dimorphecolate (Scheme 46), xerulin (Scheme 48), papulacandin D (Scheme 49), vitamin A (Scheme 60), )8- and y-carotene (Schemes 61 and 62), vitamin D (Scheme 65), reveromycin B (Scheme 67), and nakienone A (Scheme 70). In this section, attmipts have been made to catalogue most of the currently known examples of the synthesis of natural products via Pd-catalyzed alkenyl-aryl or aryl-alkenyl coupling (Table 2) and alkenyl-alkenyl coupling (Table 3). 

Nozaki-Hiyama-Kishi (NHK) reactions215,216 are well known and often employed as a useful method for the synthesis of natural products by coupling of allyl, alkenyl, alkynyl, and aryl halides or triflates with aldehydes. The organochromium reagents are prepared from the corresponding halides or triflates and chromium(ll) chloride, and are employed in polar aprotic solvents (THF, DMF, DMSO, etc.). Subsequently, it was found that nickel salts exhibited a significant catalytic effect on the formation of the C-Cr bond217,218 (Equation (19)). 

SCHEME 35. Recent syntheses of natural products via Pd-catalyzed aryl-alkenyl or alkenyl-aryl coupling... 

There are numerous examples of this type of coupling for the formation of alkenyl-aryl and alkenyl-heteroaryl bonds. Only a few examples within the context of complex natural product synthesis are highlighted here. 

They found that combination of the Ir(T) catalyzed C-H borylation and Suzuki coupling sequence led to a two-step, one-pot C-H Suzuki arylation that enabled direct transformation of the N-Boc pyrrole to the C3 arylated intermediate in 78% yield. Following installation of the required acyl group, an application of their oxidative Pd-catalyzed C-H alkenylation reaction enabled formation of the key structural architecture of the natural deliver the natural product. The orthogonal selectivity characteristics displayed by these C-H functionalization processes makes possible iterative functionalization of the heteroaromatic pyrrole core. Utilization of the highly versatile C-H borylation - Suzuki coupling to install the aromatic functionality opens up possibilities of facile analogue synthesis via this route. 

Alkylboranes 103 are easily prepared by hydroboration of 1-alkenes with 9-BBN, and subsequent reactions with aryl, alkenyl, and alkyl halides offer versatile methods of dkylation to afford alkylated products 104, 105, and 106. The hydroboration-coupling protocol has been utilized extensively in natural product syntheses [87]. 

C. SYNTHESIS OF NATURAL PRODUCTS VIA Pd-CATALYZED ALKENYL-ARYL, ARYL-ALKENYL, AND ALKENYL-ALKENYL COUPLING... 

Table 3.5 Application of the Negishi coupling to the synthesis of natural products and other compounds of medicinal and agrochemical interest aryl-alkenyl and alkenyl-aryl coupling.

The palladium-catalyzed reaction of alkenyl-, aryl-, alkynyl- and alkylsiloxanes with aryl, alkyl, and alkenyl halides and triflates in the presence of activators is known as the Hiyama cross-coupling reaction and several reviews have been published. This chapter will present major developments and examples of recent carbon-carbon bond formation methodology and improvements as well as their use in natural products synthesis in the last few years. 

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