Catalytic asymmetric alkylation

Catalytic Asymmetric Alkylation of n-Allyl Metal Complexes... 

Although several excellent examples of the catalytic asymmetric alkylation of imines have been reported, especially in the past few years, the scope of the reactions is still limited with regard to substrate generality, experimental simplicity, catalyst loading, and the enantiomeric purity of the isolated products. Research in this field has just started and further development can be expected in the near future. 

Catalytic asymmetric alkylation of 1 has also been carried out with polymer-bound glycine substrates. For example, O Donnell and coworkers used Wang resin-bound derivative 11 in combination with BEMP or BTPP and 4d, as exemplified in Scheme 2.7 [25]. Although a full equivalent of 4d was required, the promising stereoselectivities provided strong implications for further optimizations. 

This powerful quaternization method enabled the catalytic asymmetric synthesis of quaternary isoquinoline derivatives with 42 (R1 = Me) as a substrate. When 42 (R1 = Me) was treated with a,a -dibromo-o-xylene, CsOHH20 and (S,S)-le (1 mol%) in toluene at 0 °C, the transient monoalkylation product was rapidly produced, and subsequently transformed into the desired 44 (64%, 88% ee) during the work-up procedure. Catalytic asymmetric alkylation of 42 (R1 = Me) with functionalized benzyl bromide 45, followed by the sequential treatment with 1 M HC1 and then excess NaHC03, furnished the corresponding dihydroisoquinoline derivative 46 in 87% with 94% ee (Scheme 5.23) [25]. 

Scheme 6.12 Catalytic asymmetric alkylation using BINOL-derived two-center catalyst.

Scheme 6.13 Catalytic asymmetric alkylation and Michael addition using tartrate-derived two-center catalyst.

Scheme 6.15 Catalytic asymmetric alkylation using 2,2 -bimorpholinium ammonium salts.

A series of chiral C2-symmetric tridentate bis(oxazoline) 110, 112 and bis(thiazoline) 111, in which a diphenylamine unit links the two chiral ox-azolines, was used for a more practical and efficient catalytic asymmetric alkylation of indoles with nitroalkenes (Scheme 31) [104], The alkylation of indole with frarzs-P-nitrostyrene in toluene at room temperature has been accomplished with 110d-Zn(OTf)2 or 113-Zn(OTf)2 as the catalyst. The obtained results show that the NH group in ligands 110-112 is crucial. Indole... 

Catalytic asymmetric alkylations of 28 have also been carried out with polymer-bound glycine substrates [43], or in the presence of polymer-supported cinchona alkaloid-derived ammonium salts as immobilized chiral phase-transfer catalysts [44], both of which feature their practical advantages especially for large-scale synthesis. 

Dolling UH, Davis P, Grabowski EJJ (1984) Efficient catalytic asymmetric alkylations, 1. Enantioselective synthesis of (+)-indacrinone via chiral phase-transfer catalysis. J Am Chem Soc 106 446... 

Two main strategies for the catalytic asymmetric alkylation of imines are (a) chiral Lewis acid approach and (b) chiral nucleophilic approach. 

Enantioselective Alkylations and Catalytic Asymmetric Alkylations. a-Substitution of a carbonyl-containing substrate via generation of an enolate ion followed by subsequent reaction with an electrophile remains one of the most fundamental transformations in synthetic organic chemistry. A more recent advance to this type of transformation is the ability to perform this... 

Dolling, U.-H. Davis, P. Grabowski, E. J. J., Efficient Catalytic Asymmetric Alkylations. 1. Enan-tioselective Synthesis of (+)-Indacrinone via Chiral Phase-Transfer Catalysis. / Am. Chem. Soc. 1984, 106, 446. 

Hughes, D. L. Dolling, U.-H. Ryan, K. M. Schoenewaldt,E. F. Grabowski, E.J.J., Efficient Catalytic Asymmetric Alkylations. 3. A Kinetic and Mechanistic Study of the Enantioselective Phase-Transfer Methylation of 6,7-Dichloro-5-methoxy-2-phenyl-l-indanone J. Org. Chem. 1987, 52, 4745. 

Figure 14. Catalytic asymmetric alkylation of a Shiff base promoted by 15.

The addition of dialkylzinc to aldehyde proceeds smoothly in the presence of a Lewis acid. Several catalytic asymmetric alkylations catalyzed by chiral titanium complexes have been reported using dialkylzinc reagents. 

Diorganozinc reagents have a monopoly as alkylation reagents in catalytic asymmetric alkylations of aldehydes. But a few catalytic asymmetric alkylations were reported by the use of alkynylborane and trialkylaluminum species. 

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