Asymmetric regioselective

The stereochemical requirements for the synthesis were fulfilled starting from enantiomerically pure alkynes 16, whereas the regiocontrol was achieved, when necessary (the [4-1-1] annulation can afford mixtures of quinoline derivatives, see Scheme 6), using ort/ o-(trimethylsilyl)-substituted arylisonitriles 15 (Scheme 7). In conclusion, the authors set up an asymmetric, regioselective, and widely applicable protocol that allowed the synthesis of more than fifty different compounds, proving once more the broad scope and functional-group tolerance of radical reactions. 

The FMO coefficients also allow cpralitative prediction of the kinetically controlled regioselectivity, which needs to be considered for asymmetric dienes in combination with asymmetric dienophiles (A and B in Scheme 1.1). There is a preference for formation of a o-bond between the termini with the most extreme orbital coefficients ... 

The method has been applied in asymmetric and regioselective syntheses of several natural compounds. Two simple examples are the commercial syntheses of the gipsy moth hydrophobic sex attractant, disparlure (RE. Rossiter, 1981, 1985) and < mono-epoxidation of a diene in a leukotriene B4 synthesis (L.S. Mills, 1983). 

The fact that the isomeric structure of azolides is thermodynamically controlled has been used by Olofson and Kendall to prepare 1-alkylazoles regioselectively (70JOC2246). An asymmetric pyrazole yields two alkylated derivatives (Scheme 21 see Section 4.04.2.1.3 (viii)), but the alkylation with a powerful alkylating agent of the acetylated derivative leads to the less abundant isomer via the salt (249), which is too unstable to be isolated. 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

This strategy can be applied to the synthesis of vinylepoxides, since high enantioselectivity and good regioselectivity can often be obtained in asymmetric dihydroxylation of dienes, resulting in vinylic diols [24, 25], Transformation of the diols into epoxides thus represents an alternative route to vinylepoxides. This strategy was recently employed in the synthesis of (+)-posticlure (Scheme 9.6) [26]. 

Analogous results were obtained for enol ether bromination. The reaction of ring-substituted a-methoxy-styrenes (ref. 12) and ethoxyvinylethers (ref. 10), for example, leads to solvent-incorporated products in which only methanol attacks the carbon atom bearing the ether substituent. A nice application of these high regio-and chemoselectivities is found in the synthesis of optically active 2-alkylalkanoic acids (ref. 13). The key step of this asymmetric synthesis is the regioselective and chemoselective bromination of the enol ether 4 in which the chiral inductor is tartaric acid, one of the alcohol functions of which acts as an internal nucleophile (eqn. 2). 

Trost and Hachiya [140] studied asymmetric molybdenum-catalyzed alkylations. Interestingly, they noticed that the regioselectivity of this transformation performed with a non-symmetric allylic substrate varied according to the nature of the metal Pd-catalyzed substitutions on aryl-substituted allyl systems led to attack at the less substituted carbon, whereas molybdenum catalysis afforded the more substituted product. They prepared the bis(pyridylamide) ligand 105 (Scheme 55) and synthesized the corresponding Mo-complex from (C2H5 - CN)3Mo(CO)3. With such a catalyst, the allylic... 

The major problem remains control of regioselectivity in favor of the branched regioisomer. While aryl alkenes as well as heteroatom-substituted alkenes favor the chiral branched isomer, for aliphatic alkenes such an intrinsic element of regiocontrol is not available. As a matter of fact branched-selective and asymmetric hydroformylation of aliphatic alkenes stands as an unsolved problem. In this respect regio- and enantioselective hydroformy-... 

A copper salt assists the control of the regioselectivity in VNS for m-dinitrobenzene. For instance, the reaction of m-dinitrobenzene with 4-iodophenol in the presence of copper tert-butoxide gives asymmetrical biphenyl in 78% yield (Eq. 9.34).61... 

Platinum complexes with chiral phosphorus ligands have been extensively used in asymmetric hydroformylation. In most cases, styrene has been used as the substrate to evaluate the efficiency of the catalyst systems. In addition, styrere was of interest as a model intermediate in the synthesis of arylpropionic acids, a family of anti-inflammatory drugs.308,309 Until 1993 the best enantio-selectivities in asymmetric hydroformylation were provided by platinum complexes, although the activities and regioselectivities were, in many cases, far from the obtained for rhodium catalysts. A report on asymmetric carbonylation was published in 1993.310 Two reviews dedicated to asymmetric hydroformylation, which appeared in 1995, include the most important studies and results on platinum-catalogued asymmetric hydroformylation.80,81 A report appeared in 1999 about hydrocarbonylation of carbon-carbon double bonds catalyzed by Ptn complexes, including a proposal for a mechanism for this process.311... 

C02Me)CH2-C02Me was regioselectively prepared in >82% enantiomeric excess by homogeneous catalytic hydroformylation. For other vinylidene esters, the asymmetric induction was lower.318... 

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