Asymmetric tandem addition

Meyers, A. I. Licini, G. Intramolecular asymmetric tandem additions to chiral naphthyl 489 oxazolines. Tetrahedron Lett. 1989, 30, 4049-4052. 

Anisole and its derivatives have thus far demonstrated the widest variety of [Os]-mediated dearomatization reactions. These transformations have included substitutions, asymmetric tandem addition sequences, and a variety of cyclizations. 

Asymmetric tandem additions In order to further take advantage of the high degree of stereoselectivity observed in tandem additions to [Os]-arene complexes, a chiral anisole derivative has been prepared, which has demonstrated high coordination diastereoselectivity... 

Starting from earher data showing the positive role of Lewis acid for asymmetric tandem addition/allylation of unsaturated compounds derived from... 

Guo, H.C. Ma, J.A. (2006) Catalytic Asymmetric Tandem Transformations Triggered by Conjugate Additions. Angewandte Chemie International Edition, 45, 354-366. 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

The first asymmetric procedure consists of the addition of R2Zn to a mixture of aldehyde and enone in the presence of the chiral copper catalyst (Scheme 7.14) [38, 52]. For instance, the tandem addition of Me2Zn and propanal to 2-cyclohexenone in the presence of 1.2 mol% chiral catalyst (S, R, R)-1S gave, after oxidation of the alcohol 51, the diketone 52 in 81% yield and with an ee of 97%. The formation of erythro and threo isomers is due to poor stereocontrol in the aldol step. A variety of trans-2,3-disubstituted cyclohexanones are obtained in this regioselective and enantioselective three-component organozinc reagent coupling. 

Silyl enolates are useful carbon nucleophiles in the asymmetric tandem Michael addition and lactonization (Scheme 3.3). Mukaiyama recently reported that cinchona-derived ammonium phenoxides act as activators (nucleophilic catalysis), to give highly stereocontrolled products [18-20]. In a typical PTC manner, most of the... 

The synthesis of the optically active chroman 489 can be achieved by use of a catalytic asymmetric tandem oxa-Michael addition Friedel-Crafts alkylation sequence between 3-methoxyphenol and (/. (-methyl 2-oxo-4-phenylbut-3-enoate. The chiral C2-symmetric box managanese(n)- complex 490 exerts excellent stereocontrol upon the reaction (Equation 200) <20030BC1953>, whereas only moderate enantioselectivity is observed in the presence of a chiral C2-symmetric 2,2 -bipyridyl copper(n)- complex (42% = ee) <20050L901>. 

The chiral anisole derivative 37 has been used in the synthesis of several asymmetric functionalized cyclohexenes (Table 9) [22]. In a reaction sequence similar to that employed with racemic anisole complexes, 37 adds an electrophile and a nucleophile across C4 and C3, respectively, to form the cyclohexadiene complex 38. The vinyl ether group of 38 can then be reduced by the tandem addition of a proton and hydride to C2 and Cl, respectively, affording the alkene complex 39. Direct oxidation of 39 liberates cydohexenes 40 and 41, in which the initial asymmetric auxiliary is still intact. Alternatively, the auxiliary may be cleaved under acidic conditions to afford /y3 -allyl complexes, which can be regioselectively attacked by another nucleophile at Cl. Oxidative decomplexation liberates the cyclohexenes 42-44. HPLC analysis revealed high ee values for the organic products isolated both with and without the initial asymmetric group. 

Actually, repeating the tandem addition of Scheme 38 with the (R) enantiomer of Davies amide affords total control on the three created asymmetric centers, and provides the trisubstituted cyclohexane in 72% yield and as a single (1R, 2R, 6R) enantiomer (i.e. absolute configurations reported in Scheme 38)173,174. 

Tandem Asymmetric Conjugate Addition. Enantioselective conjugate addition of an organometallic reagent to a prochiral... 

Guo H-C, Ma J-A. Catalytic asymmetric tandem transformations triggered by conjugate additions. Angew. Chem., Int. Ed. 2006 45 354-366. 

Plaquevent and coworkers synthesized methyl dihydrojasmonate 28 using this methodology by performing the asymmetric Michael addition of dimethyl malonate 29 on 2-pentyl-2-cydopentenone 30 [18]. The mechanism involved the tandem deprotonation of the malonate 29 using solid-liquid phase-transfer catalysis... 

Deng also successfully applied the C6 —OH catalysts 64a,b to the asymmetric tandem conjugate addition-protonation reactions of the a-cyanoketones or... 

The continued fascination chemists possess with asymmetric synthesis provides the basis for the next four procedures. The synthesis of (R)-(-)-10-METHYL-l(9)-OCTALONE-2 is a nice demonstration of an asymmetric Michael addition by a chiral imine followed by an aldol—in short an asymmetric Robinson annulation. The asymmetric glycolization to STILBENE DIOL (R,R-l,2-DIPHENYL-I,2-ETHANEDIOL) represents an olefin oxidation using catalytic alkaloids in tandem with osmium tetroxide. As reagents for a variety of asymmetric alkylations, the preparation of 2-CYANO-6-PHENYLOXAZOLOPIPERIDINK is pavscnicd as well as another route to... 

Dihydrooxazoles are also effective ortho directors for nucleophilic addition to naphthalene and some heteroaromatic derivatives. Tandem additions result if the reaction mixtures are quenched with electrophiles (Scheme 54). When chiral oxazoles are used, asymmetric syntheses, such as that of scopadulcic acid, are achieved. Although most of the oxazoles employed have chelating groups to enhance stereoselectivity, the steric bias provided by valinol or t-leucinol derived oxazoles is often equivalent or superior. 

An aluminum-lithiiun catalyst, (R)-ALB, prepared from (R)-BINOL, and lithium aluminium hydride promoted the addition of malonate to 23 giving (R)-44 in 99% ee. X-ray analysis of the ALB catalyst showed an aluminum ate complex structure with li coordination to the oxygen atom. The asymmetric tandem Michael-aldol reaction of 46 was conducted with this catalyst giving a single isomer 47 containing three asymmetric centers. The aluminum enolate under-... 

The latter process can form part of a novel tandem addition reaction.[19c] The lack of accompanying silyl transfer is in contrast to other asymmetric Mukaiyama-type aldol reactions. [20]... 

Scheme 2.94 Catalytic asymmetric tandem conjugate addition-protonation reaction...

Wang Y, Liu XF, Deng L (2006) Dual-Function Cinchona Alkaloid Catalysis Catalytic Asymmetric Tandem Conjugate Addition-Protonation for the Direct Creation of Nonadjacent Stereocenters. J Am Chem Soc 128 3928... 

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