Stereoselective synthesis nucleophilic reactions

In the synthesis of carpamic acid (98), Mitsutaka and Ogawa have used 1,2-dihydropyridine as a starting material [80H(14)169]. Photooxygenation of dihydropyridine 8h afforded enr/o-peroxide 96. Subsequent stereoselective nucleophilic reaction of 96 with ethyl vinyl ether in the presence of tin chloride gave tetrahydropyridinol 97, which was then converted into carpamic acid (98) in six more steps. 

Addition of Alkyl and Aryl Derivatives To illustrate stereoselective syntheses in nucleophilic reactions of nitrones, the synthesis of (+ )-lentiginosine... 

A mild stereoselective synthesis of arylthioglycosides has been accomplished via anomeric inversion during the nucleophilic reaction by aryl thiols on glycosyl halides [18, 19]. 

Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim S-H, DiMarco JD, Fairchild CR, Gougoutas JZ, Lee FYF, Long BH, Vite GD. (2000) A novel application of a pd(0)-catalyzed nucleophilic substitution reaction to the regio- and stereoselective synthesis of lactam analogues of the epothilone natural products. J Am Chem Soc 122 8890-8897. 

Metallic tin, Sn(0), is even more effectively employed. For example, in the presence of Sn(0), allyl bromide and a-halocarbonyl compounds afford nucleophilic organometallic species, which add to aldehydes in good yields to give homoallylic alcohols (12) and g-hydroxycarbonyl compounds (13,14) respectively. a-Diketones could be reduced by activated Sn(0), to give tin(II) enediolates which in turn undergo aldol reaction to form a,g-dihydroxyketones (15,16). This reaction was successfully applied to a stereoselective synthesis of methyl D-glucosaminate (17). 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

Oxazoline-directed conjugate addition of nucleophiles to a naphthalene nucleus is one of the most useful methods to prepare dihydronaphthalenes. Since Meyers last comprehensive review, the focus has been directed to stereoselective synthesis of these important compounds. Meyers laboratory has continued their preeminence in this field and has expanded the scope and applications of this reaction. 

A highly regio- and stereoselective synthesis of oxepine derivatives via cyclization of bromoallenes bound with hydroxy group by a four-carbon atom tether in the presence of a palladium(O) catalyst and alcohol is developed (Equation 16). In this reaction, the bromoallenes act as an allyl dication equivalent, and the intramolecular nucleophilic attack takes place exclusively at the central carbon atom of the allene moiety <2004JA8744>. 

The stereoselective synthesis of 1,4-disubstituted-l,3-dienes proceeds by head-to-head oxidative coupling of two alkynes with formation of an isolable metallacyclic biscarbene ruthenium complex [23], as shown in Scheme 6. Several key experiments involving labeled reagents and stoichiometric reactions and theoretical studies support the formation of a mixed Fischer-Schrock-type biscarbene complex which undergoes protonation at one carbene carbon atom whereas the other becomes accessible to nucleophilic addition of the carboxylate anion (Scheme 6) [23]. 

An alternative stereoselective synthesis of chiral heterocycles based on carbohydrate-induced stereodifferentiation includes nucleophilic addition reactions on heterocyclic systems already bound to the carbohydrate auxiliary. An example of this strategy has been shown by stereoselective addition of Grignard reagents to carbohydrate-linked 4-pyridones [61]. For this purpose, trimethylsiloxypyridine was glycosylated regioselectively using pivaloyl-protected glycosyl fluorides. 

Nucleophilic substitution of a,/3-epoxysilanes followed by the Peterson elimination is valuable for the stereoselective synthesis of alkenes.3 The reactions with lithium phenylsulfide and diphenylphosphide form alkenyl sulfides and alkenylphosphines, respectively, in a stereospecific manner. 7-Metallo-a,/ -epoxysilanes are isomerized to a-siloxyallylmetals by anionic ring opening and subsequent Brook rearrangement (Equation... 

Allylic alcohols can serve as 7t-allyl cation precursors to act as electrophiles in Sn reactions with a tethered O-nucleophile giving rise to the formation of spiroannulated tetrahydrofurans <2000TL3411>. Michael acceptors are also suitable electrophiles for the cyclization to tetrahydrofuran rings <2003T1613>. The Tsuji-Trost allylation has found widespread application in the synthesis of carbo- and heterocyclic compounds. Allylic substitution has been employed in the stereoselective synthesis of 2-vinyl-5-substituted tetrahydrofurans <2001H(54)419>. A formal total synthesis of uvaricin makes twofold use of the Tsuji-Trost reaction in a double cyclization to bis-tetrahydrofurans (Equation 73) <20010L1953>. 

Nucleophilic addition of ester enolates to enantiopure nitrones, followed by cyclization of the resulting hydro-xylamine, is a general approach to isoxazolidin-5-ones and can be applied to the stereoselective synthesis of these heterocycles <2005CRC775>. In some cases, the cyclization occurs spontaneously under the reaction conditions. For example, the addition of the sodium enolate of methyl acetate to chiral nitrone 551 gave directly the isoxazolidin-5-ones 552 in quantitative yield and high ty -diastereoselectivity (Equation 91) <1998CC493>. 

Thermal degradation led to the oxo compounds including [(N02)N0)][Ti0(F3CS03)4], Tilv triflate complexes efFiciently catalyze a variety of reactions including the conversion of acetophenones to 1,3,5-triarylbenzenes,658 the nucleophilic ring opening of epoxides,659 Diels—Alder reactions,660 selective Claisen and Dieckmann ester condensations,661 esterification reactions,662 Fries rearrangements,663 homoaldol reactions,664 sequential cationic and anionic polymerizations,641 and the stereoselective synthesis of m-arabinofuranosides.606... 

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