Sequential Assembly Strategy for Tetrasubstituted Olefin Synthesis Using Vinyl 2-Pyrimidyl Sulfide as a Platform

Abstract

We have developed a programmable and diversity-oriented synthetic scheme for tetrasubstituted olefins through a site-selective and sequential assembly of pi-components onto a C=C core of vinyl 2-pyrimidyl sulfide. Noteworthy features are that (i) all components assembled stem from readily available organic halides or their Grignard reagents, (ii) the installation at the desired position can be achieved by the addition of the components in the appropriate order, and (iii) simple alteration of addition order in the sequence results in the production of all possible regio- and stereoisomers of multisubstituted olefins.

Palladium-catalyzed desulfinylative C–C allylation of Grignard reagents and enolates using allylsulfonyl chlorides and esters

“…29 We have also shown that aliphatic sulfonyl chlorides are also excellent electrophiles. 31 Among the earliest, most economical and useful nucleophilic partners are the Grignard reagents, which can be coupled with all kinds of electrophilic partners such as sulfides, [32][33][34][35][36][37][38][39] sulfoxides 32,40 sulfoximines, [41][42][43][44][45] sulfones, 46-52 sulfonic esters, [53][54][55] and sulfonamides 56 in the presence of nickel catalysts.…”

Directed Mizoroki–Heck Reactions

“…Sequential amino-directed, regioselective Mizoroki-Heck arylations by Hallberg [41] During the quest for such useful platforms, Itami and Yoshida [41][42][43][44] independently developed the two versatile starting materials 29 (Scheme 7) [45,46] and 32 (Scheme 8) [47]. Both the 2-pyridyl and the 2-pyrimidyl group are excellent directing groups but, more importantly, these authors smartly connected these groups to the C -C double bond employing synthetically useful tethers.…”

“…The silicon tether of the vinylsilane 29 is a simple placeholder for hydrogen (protodesilylation) or a useful functional group for subsequent Hiyama cross-coupling reactions [45,46,48]. Similarly, the C -S linkage in 32 cross-couples with Grignard reagents under palladium catalysis [47].…”

A Reusable Palladium/Cationic 2,2′-Bipyridyl System-Catalyzed Double Mizoroki-Heck Reaction in Water

“…Palladium-catalyzed double Mizoroki-Heck coupling of aryl halides with olefins might be the most convenient method to fulfill the formation of β,β-diaryl substituted alkenes, due to the use of low catalyst loading and a large variety of reactants, which are commercial available. Palladium-phosphine [15][16][17][18][19][20][21], -carbene [22], and -arylurea [23,24] complexes, as well as Pd(OAc) 2 [25,26], have been applied in this reaction, using organic solvents as the reaction medium. Alternatively, supported Pd complexes have also been used as catalysts for β,β-double arylation of α-olefins.…”