Phosphines chiral, Lewis bases

A ternary soft Lewis-acid/hard Bronsted-base/hard Lewis-base catalytic system for the direct catal5rtic enantioselective addition of allyl cyanide 37 to ketones to give tertiary alcohols with a Z-olefin (38) has been developed by Shibasaki (Scheme 2.24). Mechanistic studies revealed that Cu(i)/chiral phosphine ligand 35 and Li(OC6H4-p-OMe) serve as a soft Lewis acid and a hard Bronsted base, respectively, allowing for deprotonative activation of 37 as the rate-determining step. The hard Lewis base, bis(phosphine oxide) 36,... 

A range of Lewis bases catalyse the addition of TMSCN to aldehydes, with phosphines and amines the most efficient.247 Kinetic studies indicate that the orders of aldehyde, Lewis base (LB), and TMSCN are 1, 1, and 0, suggesting an Me3Si-LB+ CN ion pair as an intermediate. However, chiral phosphines and amines gave very... 

Asymmetric organocatalytic Morita-Baylis-Hillman reactions offer synthetically viable alternatives to metal-complex-mediated reactions. The reaction is best mediated with a combination of nucleophilic tertiary amine/phosphine catalysts, and mild Bronsted acid co-catalysts usually, bifunctional chiral catalysts having both nucleophilic Lewis base and Bronsted acid site were seen to be the most efficient. Although many important factors governing the reactions were identified, our present understanding of the basic factors, and the control of reactivity and selectivity remains incomplete. Whilst substrate dependency is still considered to be an important issue, an increasing number of transformations are reaching the standards of current asymmetric reactions. 

Shi, M., Chen, L.-H. Chiral phosphine Lewis base catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone and phenyl acrylate. Chem. Commun. 2003,1310-1311. 

In the preceding examples, the asymmetric catalyst is a Lewis acid and hence the catalytic processes reported so far involve electrophilic activation by a metal-centred chiral Lewis acid. There is another strategy, although less explored, which consists of designing chiral Lewis bases for nucleophilic catalysis. It is well known that Lewis bases such as nitrogen heterocycles and tertiary phosphines and amines catalyse a variety of important chemical processes. For instance 4-(dimethylamino)pyridine (DMAP) catalyses the acylation of alcohols by anhydrides the mechanism by which DMAP accelerates this process provides an instmctive illustration of how nucleophiles can... 

In addition, we also found that upon using stronger Lewis bases such as PPhMc2 or PR3 (R = Bu, Me) as promoters in the reaction of A -arylidenedi-phenylphosphinamides 212 with methyl acrylate, phenyl acrylate or PVK, the double aza-MBH adducts 218 and 219 and the abnormal aza-MBH adducts 220 or 221, derived from further reactions of the double adducts, can be obtained either as the major products or as the sole products depending on the reaction conditions (Scheme 2.108). Initial investigations of a catalytic asymmetric version of this reaction in the presence of chiral amine and phosphine Lewis bases have been disclosed (Scheme 2.109)." ... 

In 2003, we first demonstrated that l,l -bi-2,2 -naphthol (BINOL)-derived chiral LBBA (Lewis base and Bronsted add) bifunctional phosphine CP17 (LB = PPhs, BA = Ph-OH) could be used as an effective catalyst in asymmetric aza-MBH reaction of A-tosylimines with MVK and phenyl acrylate, affording the corresponding adducts in good yields with high ees (Scheme 2.119). The addition of molecular sieves increased chemical yields because they removed the ambient moisture that caused the decomposition of A-sulfonated imines. The asymmetric induction of this catalyst is comparable to that of the quinidine... 

Figure 2.9 Bifunctional chiral phosphine Lewis bases for use as catalysts.

Lewis base or nucleophilic catalysis by chiral amines, amine or phosphine iV-oxides, sulfides, and phosphines has been intensively exploited in asymmetric organocatalysis [122]. Representative catalysts are shown in Figure 2.27. 

A new catalyst incorporating chiral thiourea and nucleophilic Lewis base showed efficiency in the asymmetric BH reactions. The use of a binaphthyl-based amino-thiourea catalyst 63 synthesized by Wang et al. [ 114] resulted in good yields and enantioselectivities in the reaction of cyclohexenone and aldehydes. Another amino-thiourea 12 was demonstrated as an efficient bifunctional catalyst for the enantio-selective aza-BH reaction of (3-methyl-nitrostyrene and iV-tosyl-aldimines, affording P-nitro-y-enamines in modest to excellent enantioselectivities and diastereoselec-tivities (Scheme 9.32). It was found that no reaction occurred in the absence of the methyl group of nitroalkene [115]. A similar phophine-thiourea catalyst 64 was reported in 2008 by Wu and co-workers [116] and turned out to be efficient in the asymmetric BH reaction of MVK and aldehydes, providing fast reaction rate, good yields, and excellent enantioselectivities (87-94% ee). More recently, aL-threonine-derived phosphine-thiourea catalyst 65 was readily synthesized by Lu and coworkers [117] and applied in the enantioselective BH reaction of aryl aldehyde with methyl acrylate. 

A clearly innovative catalytic system was reported by Nakajima and co-workers [48], who introduced chiral phosphine oxides as suitable Lewis bases for activating trichlorosilane in stereoselective transformations. Indeed trichlorosilane has been used in the conjugate reduction of a,p-unsaturated ketones in the presence of a catalytic amount of a chiral Lewis base. The reduction of 1,3-diphenylbutenone promoted by catalytic amounts of 2,2 -bis(diphenylphosphanyl)-l,l -binaphthyl dioxide (Cat. 15, BINAPO) at 0°C led to the corresponding saturated compound in 97% yield and a somehow surprising, but very good, 97% ee (Scheme 15.19). 

An unsymmetrical salen ligand bearing a Lewis base catalyses Ti(OPr-i)4-promoted addition of TMSCN to benzaldehyde with as little as 0.05 mol% loading, quantitative conversion is achieved in 10 min at ambient temperature. Another salen catalyst - a bifunctional salen-phosphine oxide-Ti(IV) combination - promotes enantioselective cyanosilylation of aldehydes. Fine tweaking of the structure of another series of bifunctional chiral salen-Ti(IV) complexes allows the enantioselectivity to be reversed. Biaryl-bridged salen-titanium complexes are also highly efficient catalysts, one example giving 87% ee at room temperature. ... 

It has been also found that chiral phosphine oxides (5)-BINAPO catalyzed silicon tetrachloride-mediated, enantioselective phosphonylation of aldehydes with trialkyl phosphites, led to formation of optically active a-hydroxyphosphonates with low to moderate enantioselectivities (ee 22-52%)7 This reaction constituted the first example of asymmetric Abra-mov-type phosphonylation of aldehydes with trialkyl phosphites catalyzed by chiral Lewis bases. 

Shibasaki and coworkers developed a bifunctional chiral catalyst possessing the Lewis acid (aluminum metal) and the Lewis base (phosphine oxide), which was successfully applied to asymmetric Reissert-type reaction of trimethylsilylcyanide (TMSCN) [45]. The reaction of quinoline (92) with TMSCN and 2-furoyl chloride in the presence of Lewis acid Lewis base catalyst (91) occurred to give the Reisser product in 91% yield and 85% ee. The chiral catalyst was connected to JandaJRL... 

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