Nucleophiles catalytic asymmetric addition

Vinylsilane to copper transmetallation has entered the literature,93 93a,93b and a system suitable for catalytic asymmetric addition of vinylsilanes to aldehydes was developed (Scheme 24).94 A copper(l) fluoride or alkoxide is necessary to initiate transmetallation, and the work employs a copper(ll) fluoride salt as a pre-catalyst, presumably reduced in situ by excess phosphine ligand. The use of a bis-phosphine was found crucial for reactivity of the vinylcopper species, which ordinarily would not be regarded as good nucleophiles for addition to aldehydes. The highly tailored 5,5 -bis(di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino-4,4 -bis(benzodioxolyl) (DTBM-SEGPHOS) (see Scheme 24) was found to provide the best results, and the use of alkoxysilanes is required. Functional group tolerance has not been adequately addressed, but the method does appear encouraging as a way to activate vinylsilanes for use as nucleophiles. 

The alkaloid-catalyzed addition of alcohols to prochiral ketenes is one of the very first examples of catalytic asymmetric synthesis. In pioneering work by Pracejus in the 1960s quite remarkable 76% ee was achieved and it was not until 1999 that substantial improvement of enantioselectivity in catalytic asymmetric addition of O- and N-nucleophiles to prochiral ketenes was reported. In particular, the chiral... 

The nucleophiles discussed above can also react with the C=N group and the final section of this chapter describes the many recent advances in the catalytic asymmetric additions to imines using both metal complexes and also organocatalysts. 

Nucleophilic additions to imines are generally more challenging than additions to carbonyls, owing to the lower electrophilicity of the imine and the greater propensity for a-deprotonation. Furthermore, stereoselective processes may be complicated by the presence of synlanti imine isomers. Nevertheless, the direct, enantioselective synthesis of substituted amines is an attractive goal and, while catalytic asymmetric additions to imines are less developed than the corresponding... 

S)-BINOL-Ti was also shown to be an effective chiral catalyst for the catalytic asymmetric addition of alkynylzinc to inactivated simple ketones with good to excellent enantioselectivities [63] (Scheme 14.12). The same reaction has been furnished by using lithium phenylacetylide as the nucleophile under the catalysis of titanium complex prepared from BINOL and ClTi(O Pr)3 [64]. 

Catalytic Asymmetric Addition Reactions of Cu(I)-Conjugated Soft Carbon Nucleophiles... 

The asymmetric addition of different types of nucleophiles at the C-l position of 3,4-dihydroisoquinolines were highlighted in a number of publications. Schreiber et al. described an enantioselective addition of terminal alkynes 136 to 3,4-dihydroisoquinolinium bromide 137 in the presence of triethylamine, catalytic copper bromide, and QUINAP <06OL143>. The resulting 1-substituted tetrahydroquinolines 138 were isolated in high yield and high enantiomeric excess in most cases. 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

This section focuses on the preparation of fluorinated compounds through asymmetric hydrogenation/reduction reactions and nucleophilic additions by listing some examples. The first successful example of catalytic asymmetric hydrogenation of a fluoro-compound was reported by Konig et al.81... 

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

In the presence of thiourea catalyst 122, the authors converted various (hetero) aromatic and aliphatic trons-P-nitroalkenes with dimethyl malonate to the desired (S)-configured Michael adducts 1-8. The reaction occurred at low 122-loading (2-5 mol%) in toluene at -20 to 20 °C and furnished very good yields (88-95%) and ee values (75-99%) for the respective products (Scheme 6.120). The dependency of the catalytic efficiency and selectivity on both the presence of the (thio) urea functionality and the relative stereochemistry at the key stereogenic centers C8/C9 suggested bifunctional catalysis, that is, a quinuclidine-moiety-assisted generation of the deprotonated malonate nucleophile and its asymmetric addition to the (thio)urea-bound nitroalkene Michael acceptor [279]. 

Until then, only heterogeneous catalyst had been successful. However, in the mid-1980s, the work of Ito et al. led to an outstanding discovery in a catalytic asymmetric aldol reaction. In this case, enantioselectivity was given by a chiral ferrocene diphosphine ligand, with a carbon nucleophile addition to a carbonyl... 

The nucleophilic addition of organometallic reagents to imines provides an attractive route to amines [4]. Recendy, however, some completely different approaches to the synthesis of a-aryl amine were reported. Hayashi and Ishigeda-ni found a new catalytic system for the asymmetric addition of arylstannanes to imines derived from aromatic aldehydes (Scheme 11) [20]. 

D.3. CATALYTIC ASYMMETRIC MICHAEL ADDITION OF STABILIZED CARBON NUCLEOPHILES... 

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