Bifunctional chiral phosphine

Scheme 5.24 Bifunctional chiral phosphines as catalysts in the aza-MBH reaction with imines and MVK.

Figure 2.7 Bifunctional chiral phosphine amides for use as catalysts.

Furthermore, two recent reports were published concerning bifunctional chiral phosphine catalysts 69 and 70. In both cases, N-sulfonated imines and methyl vinyl ketone in the presence of either catalyst afforded the (5)-adducts 68b,c and 71-73 in high yields with excellent enantioselectivities. 

According to another NMR study, the mechanism of bifunctional activation in the asymmetric aza-Morita-Baylis-Hillman reaction (Scheme 7) involves rate-limiting proton transfer (116) in the absence of added protic species155 (in consonance with the report summarized in Scheme 5144), but exhibits no autocatalysis. Addition of Brpnsted acids led to substantial rate enhancements through acceleration of the elimination step. Furthermore, it was found that phosphine catalysts, either alone or in combination with protic additives, can cause racemization of the reaction product by proton exchange at the stereogenic centre. This behaviour indicates that the spatial arrangement of a bifunctional chiral catalyst for the asymmetric aza-Morita-Baylis-Hillman reaction is crucial not only for the stereodifferentiation within the catalytic cycle but also for the prevention of subsequent racemization.155... 

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. 

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. ... 

In the preceding Sections it was described that chiral phosphine-rhodium complexes are effective in causing stereoselective addition of a hydrosilane to a variety of prochiral carbonyl compounds to give silyl ethers of the corresponding alkanols with fairly high enantiomeric bias at the carbon atom. The present section describes an application of the catalytic asymmetric hydrosilylation of ketones to the preparation of some new asymmetric bifunctional organosilanes. 

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... 

For example, the first chiral phosphine-catalyzed [3+2] cycloaddition has been reported in 1997 by Zhang s group [95] (Schane 6.33A), and a variety of different chiral phosphine catalysts and apphcations thereof have been reported over the last years [94], Besides monofunctional catalysts, also bifunctional phosphines like the amino add-derived 197 have been successfully designed and apphed for challenging reactions recently [96], and this additional noncova-lent coordination site turned out to be highly beneficial to obtain good selectivities in these transformations. Chiral sulfides have emerged as powerful catalysts to facihtate catalytic stereoselective Corey-Chaykovsky-type epoxida-tion, cyclopropanation, or aziridination reactions (for an early example in this field, see Scheme 6.33C) [97,98],... 

Shibasaki et al. developed a polymer-supported bifunctional catalyst (33) in which aluminum was complexed to a chiral binaphtyl derivative containing also two Lewis basic phosphine oxide-functionahties. The binaphtyl unit was attached via a non-coordinating alkenyl Hnker to the Janda Jel-polymer, a polystyrene resin containing flexible tetrahydrofuran-derived cross-Hnkers and showing better swelling properties than Merifield resins (Scheme 4.19) [105]. Catalyst (33) was employed in the enantioselective Strecker-type synthesis of imines with TMSCN. 

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

Shioji K, Tashiro A, Shibata S, Okuma K (2003) Synthesis of bifunctional P-chiral hydroxy phosphinates lipase-catalyzed stereoselective acylation of ethyl (1-hydroxyalkyl) phenylphosphinates. Tetrahedron Lett 44 1103-1105... 

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... 

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. 

Aromatic ketimines are reduced enantioselectively to amines (50 atm H2/toluene/65°C/24h), using a cooperative catalysis involving Knolker s iron complex and a BINOL-derived hydrogen phosphate auxiliary, with P-NMR evidence supporting the bifunctional catalysis. A phosphine-free chiral cationic ruthenium complex catalyses enantioselective hydrogenation of IV-alkyl ketimines, including many heretofore problematic substrates. 0... 

---