Catalytic enantioselective alkylation

Woodward and co-workers recently achieved catalytic enantioselective alkylation of aldehydes with (R3Al)2 DABCO complexes or R3A1 (R = Me or Et) in the presence of Ni(acac)2/Feringa s ligand 196 (Equation (81 )).439... 

There are only a few reports on chiral phase transfer mediated alkylations". This approach, which seems to offer excellent opportunities for simple asymmetric procedures, has been demonstrated in the catalytic, enantioselective alkylation of racemic 6,7-dichloro-5-methoxy-2-phenyl-l-indanone (1) to form ( + )-indacrinone (4)100. /V-[4-(tnfluoromethyl)phenylmethyl]cinchoninium bromide (2) is one of the most effective catalysts for this reaction. The choice of reaction variables is very important and reaction conditions have been selected which afford very high asymmetric induction (92% cc). A transition state model 3 based on ion pairing between the indanone anion and the benzylcinchoninium cation has been proposed 10°. 

Catalytic Enantioselective Alkylation / 258 Diastereomeric Interaction of Enantiomers / 278 Effects on Solid-State Properties / 279 Effects in Solution / 281 References / 293... 

The last five years have witnessed explosive advances in the development of catalytic enantioselective alkylation of imines. This chapter collects some of the important advances that have taken place during the past few years in catalytic enantioselective alkylation of imines. 

Catalytic Enantioselective Alkylation of Imines with Organozinc Reagents... 

In 1999, in consideration of the readily structural modifications and fine-tuning of catalysts to attain sufficient reactivity and selectivity, Maruoka and coworkers designed and prepared the structurally rigid, chiral spiro ammonium salts of type 1 derived from commercially available (S)- or (R)-1,1 -bi-2-naphthol as a new C2-symmetric chiral phase-transfer catalyst, and successfully applied this to the highly efficient, catalytic enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester under mild phase-transfer conditions (Scheme 5.1) [7]. 

An easy and simple synthesis of different chiral fran -l-arenesulfonylamino-2-isoborneolsulfonylaminocyclohexane derivatives (41) has been reported.108 These ligands have proved to be excellent promoters for the catalytic enantioselective alkylation and arylation of ketones (up to 99% ee), very good for the alkenylation process, and modest for the allylation and alkynylation reactions. 

Enders D, Diez E, Fernandez R, Martin-Zamora E, Munoz JM, Pappalardo RR, Lassaletta JM (1999) J Qrg Chem 64 6329 Enders D, Schubert H (1984) Angew Chem Int Ed Engl 23 365 Ferraris D, Young B, Cox C, Dudding T, Drury HI WJ, Ryzhkov L, Taggi AE, Lectka T (2002) Catalytic, enantioselective alkylation of alpha-imino esters the synthesis of nonnatural alpha-amino acid derivatives. J Am Chem Soc 124 67-77... 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

Catalytic Enantioselective Alkylation of Aldehydes with Dialkylzincs . The chiral M,M-dialkylnorephedrines, analogs of (1), are highly efficient catalysts for the enantioselective addition of dialkylzincs to aliphatic and aromatic aldehydes. Optically active aliphatic and aromatic secondary alcohols with high ee are obtained using N,fV-dialkylnorephedrines (4-6 mol%) as chiral catalyst precursors. When (lS,2/J)-MN-dialkylnorephedrine is used as a chiral catalyst precursor, prochi ral aldehydes are attacked at the si face to afford (S)-alcohols (when the priority order is R >R2)(eq7). 

Catalytic Enantioselective Alkylation of Olefins with Alkylmagnesium Halides... 

Although quite specific, these two contributions of Itsuno and co-workers constitute an interesting example of organometalHc/chiral Hgand interaction for the catalytic enantioselective alkylation of imines [24]. 

All of catalytic enantioselective alkylations of imines that have been described up to this point used homogeneous chiral catalysts. In an effort to facilitate the separation process of the product from the reaction mixture, Soai and co-workers have employed copolymers of norephedrine for the enantioselective addition of diethylzinc to a phosphinoyl imine [35c]. 

Lectka and co-workers have simultaneously developed similar phosphine-transition metal catalysts for the same transformation [54a, 54b, 54c, 54d]. These researchers were interested in testing the reactivity of a-imino esters toward enol silane nucleophiles upon chelation with a late transition metal (Ag(I), Cu(I), Ni(II), and Pd(II)) as a means of substrate activation. This ultimately led to the development of a catalytic, enantioselective alkylation of a-imino esters with enol silanes in up to 98% ee and in high chemical yields (Scheme 28). 

Catalytic Enantioselective Alkylation of Alkenes with Alkylmagncsium Halides 114... 

Catalytic enantioselective alkylation of thiophene 2-carbaldehyde using dialkylzinc reagents has led to the alcohols in good chemical yield and high optical purity <9iJCS(Pl)25>. Thus, reaction of the aldehyde with diethylzinc in the presence of ( )-(—)-l-(-butyl-2-piperidinoethanol (2 mol %) gave the product (i )-l-(2-thienyl) propan-l-ol (489) in 90% yield and 95% ee. 

Reactions catalyzed by phosphazenes have also been described. The catalytic enantioselective alkylation of the amino acid intermediate Ph2C = NCH2C02-t-Bu by alkyl halides was reported to occur efficiently in the presence of BEMP or BTTP [52], and such bases catalyze Michael additions in non-aqueous [53] and aqueous media [54]. Methyl [55] and butyl [56] methacrylates are anionically polymerized using a phosphazene base as an initiator in the presence of an ester that is apparently deprotonated in the process. Functioning as promoters in the... 

Platinum complexes have been applied by Glueck and co-workers in catalytic enantioselective alkylation of racemic secondary phosphines. The basic studies were conducted using the reaction depicted in Scheme 6.34. 

Within the area of PTC, purely synthetic chiral quaternary oninm salts have also been developed. For example, in 1999 Marnoka and co-workers prepared structurally rigid, chiral spiroammoninm salts of type 107 as new C2-symmetric phase-transfer catalysts and successfully applied them to the highly efficient, catalytic enantioselective alkylation of 106 under mild conditions. In general, 1 mol% of 107 promotes efficient alkylation, although the catalyst loading can be reduced to 0.2mol% without a decrease in ee (Scheme 18). 

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