Solvents asymmetric Heck reactions

Ohrai K, Kondo K, Sodeoka M, Shibasaki M. Effects of solvents and additives in the asymmetric Heck reaction of alkenyl triflates catalytic asymmetric synthesis of decalin derivatives and determination of the absolute stereochemistry of (+)-vemolepin. J. Am. Chem. Soc. 1994 116(26) 11737-11748. 

Overman s group [71,72] enlisted an intramolecular Heck reaction to form a quaternary center in their efforts toward ( )-gelsemine. When the cyclization precursor 70 was submitted to the ligandless conditions [Pd2(dba)3, Et3N] in the weakly coordinating solvent toluene, the quaternary center was formed as a 9 1 ratio of diastereomers (72 71 = 89 11). Addition of a silver salt in polar solvent THF completely reversed the sense of asymmetric induction in the cyclization reaction (72 71 = 3 97). 

Ionic solvents have been used to facilitate the Heck reaction (13-9), the oxidation of alcohols with hypervalent iodine reagents (19-3)," and the catalytic asymmetric dihydroxylation of olefins (15-48) using a recoverable and reusable osmium/... 

Two new fluorous chiral 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl (BINAP Table 15.1, entries 11 and 12) ligands were synthesized and their efficiency was demonstrated in an asymmetric Mizoroki-Heck reaction (Scheme 15.8) [74-76]. Aryl triflates 38 were coupled with 2,3-dihydrofuran (39) to (i )-40 in up to 93% ee. Either pure fluorous solvents or mixtures of fluorous and nonfluorous solvents were applied. Ligand 34 was compared with conventional BINAP, with the fluorous ligand giving lower reaction rates and a similar level of enantioselectivity in 24-77 h reaction time [74, 75]. The catalyst could not be recovered by reverse-phase silica gel chromatography due to its oxidation. 

A variety of other reaction variables, such as the solvent, base and various additives, can have profound effects on asymmetric Mizoroki-Heck cyclizations. These factors have been discussed in recent reviews [3]. The reaction temperature can also play an important role. At temperatures above 100 °C, catalyst decompositiou can contribute to deterioration of enantioselectivity [23, 24], Nonetheless, there are numerous examples of successful asymmetric Mizoroki-Heck cyclizations at higher temperature. Carrying out palladium-catalysed reactions in microwave reactors is now common [25], with several examples of microwave-accelerated asymmetric Mizoroki-Heck reactions being reported [26, 27]. Under microwave heating conditions, reaction times can be reduced and rigorous exclusion of oxygen is often not required. This technology was used to promote an asymmetric Mizoroki-Heck cyclization in the recent total synthesis of minliensine (see Section 16.4.4). 

Further optimization of asymmetric Mizoroki-Heck cyclizations of prochiral vinyl triflates focused on the effects of base, solvent and additives [30, 31]. Tertiary amine bases, such as -Pr2NEt, gave results inferior to those realized with K2CO3. In the absence of additives, reactions in toluene gave superior yields to reactions conducted in 1,2-dichloroethane (DCE) or polar solvents. However, additives such as tertiary alcohols (e.g. pinacol) or KOAc... 

---