Enantioselectivity, coupling with

The precatalyst 17 produced (S)-benzoin (6, Ar = Ph) in very good yield (83%) and enantioselectivity (90% ee). The condensation of numerous other aromatic aldehydes 4 yielded the corresponding a-hydroxy ketones 6 with excellent ee-values of up to 95%. (For experimental details see Chapter 14.20.2). Electron-rich aromatic aldehydes gave consistently higher asymmetric inductions than electron-deficient (i.e., activated) aromatic aldehydes, with lower reaction temperatures or lower amounts of catalyst leading to slightly higher enantioselectivities coupled with lower yields. 

Recently, other oxazole-type ligands have been used in such enantioselective couplings with very good success [413]. 

Larhed et al. investigated enantioselective Heck reactions with 2,3-dihydrofuran as alkene [86]. In the coupling with phenyl triflate, conditions previously reported by Pfaltz [87] were attempted under microwave irradiation. Interestingly, the catalytic system Pd2(dba)3/(4S)-4-t-butyl-2-[2-(diphenylphosphanyl)phenyl]-4,5-dihydro-l,3-oxazole, identified by the Swiss team, was found suitable for high-temperature microwave-assisted enantioselective Heck reactions (Scheme 76). Using a proton sponge as a base and benzene as a solvent gave the best conversions (Scheme 76). At tempera-... 

Entries 4 and 5 are examples of use of the Sakurai reaction to couple major fragments in multistage synthesis. In Entry 4 an unusual catalyst, a chiral acyloxyboronate (see p. 126) was used to effect an enantioselective coupling. (See p. 847 for another application of this catalyst.) Entry 5 was used in the construction of amphidinolide P, a compound with anticancer activity. 

Scheme 8.11 Enantioselective coupling of N-Boc pyrrolidine with aryl bromide 3.

The consistent observation of the arylated products with 92% ee confirms that the enantioselectivity of the asymmetric deprotonation was preserved during the transmetalation with ZnCl2 and retained during the Pd-catalyzed coupling. In fact, the Negishi coupling with 3-bromopyridine (entry 16) was performed at 60 °C, and still provided 26m in 92% ee, which constitutes a formal total synthesis of (R)-nicotine [27]. 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

Para-enriched hydrogen offers considerable advantages for the NMR identification of transient intermediates [12d, 34]. PHIP experiments carried out in situ under PASADENA conditions are especially powerful in this regard. The PHA-NEPHOS [MM]-derived Rh catalyst is unusually reactive, with turnover possible even at —40°C. This high reactivity, coupled with good enantioselectivity, provides an ideal case for characterizing the elusive Rh dihydrides. 

The study of the enantioselective hydrosilylation reaction was performed with a series of combined quantum mechanics/molecular mechanics (QM/MM) calculations [26, 30] within the computational scheme of ab initio (AIMD) (Car-Parrinello) [62] molecular dynamics. The AIMD approach has been described in a number of excellent reviews [63-66], AIMD as well as hybrid QM/MM-AIMD calculations [26, 47] were performed with the ab initio molecular dynamics program CPMD [67] based on a pseudopotential framework, a plane wave basis set, and periodic boundary conditions. We have recently developed an interface to the CPMD package in which the coupling with a molecular mechanics force field has been implemented [26, 68],... 

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