Stoichiometric reactions stereoselectivity

The stoichiometric reaction of lithium dialkylcuprates in diethyl ether with a-substituted /J-methylallyl sulfoxides and sulfones gives the /-substitution product with high regio- and E stereoselectivity82. The reaction provides a stereoselective method for the synthesis of trisubsti-tuted (TQ-olefins. 

For both catalytic and stoichiometric reactions, each step of the process taking place on the metal can be influenced by the nature of ligands, cations, anions, or solvent. The effects of these factors on reaction rate, selectivity, stereoselectivity, etc. cannot be easily predicted, because each step can be influenced in different ways. The reader is referred to the literature cited below. 

Ruthenium complexes do not have an extensive history as alkyne hydrosilylation catalysts. Oro noted that a ruthenium(n) hydride (Scheme 11, A) will perform stepwise alkyne insertion, and that the resulting vinylruthenium will undergo transmetallation upon treatment with triethylsilane to regenerate the ruthenium(n) hydride and produce the (E)-f3-vinylsilane in a stoichiometric reaction. However, when the same complex is used to catalyze the hydrosilylation reaction, exclusive formation of the (Z)-/3-vinylsilane is observed.55 In the catalytic case, the active ruthenium species is likely not the hydride A but the Ru-Si species B. This leads to a monohydride silylmetallation mechanism (see Scheme 1). More recently, small changes in catalyst structure have been shown to provide remarkable changes in stereoselectivity (Scheme ll).56... 

Olefins react directly at the electron-rich and rather electron-deficient oxygens. If the dimer is much more reactive toward olefins than the monomer, only a small fraction of the alkaloid-Os04 complex need be present as a dimer (94a). Houk developed a symmetrical five-membered transition-structure model on the basis of X-ray crystal structures of Os04-amine complexes and osmate ester products and ab initio transition structures of analogous reactions (Scheme 40). The MM2 calculations based on this [3 + 2] reaction model reproduce the stereoselectivities of the stoichiometric reactions observed with several chiral diamines (94b). The transition state may be stabilized by tt-tt interaction of the alkene substrate and the ligand aromatic ring (95). 

Ni alkoxide as a stoichiometric reaction. However, in this reaction the silylnickel alkoxide 76 is formed, and its reductive elimination affords silyl ethers 77 and 78. At the same time, Ni(0) is regenerated to make the reaction catalytic. The formal total synthesis of elaeokanine C (79) was carried out by this reaction [25], Homoallylic alcohol 81 is obtained by the intermolecular reaction of benzaldehyde with the diene 80 and hydrosilane in high regio- and stereoselective manner [26],... 

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]. 

Deprotonation of 4-f-butyl cyclohexanone 28 with chiral lithium amide 39 (30 mol%) and bulk base 107 (240 mol%) in the presence of HMPA (240 mol%) and DABCO (150 mol%), under external quench conditions, resulted in 79% ee of the silyl enol ether 29 (Scheme 79)121. This stereoselectivity is only slightly lower than that of the stoichiometric reaction (81% ee). 

The reaction of (—)-151 with imines such as 2-methyl-l-pyrrolidine illustrated in Scheme 33 affords complex 222. An X-ray structure of 222 shows that the coordinated imine is oriented perpendicular to the 1,2-azaborolyl ring. This orientation which contrasts with that assumed for 219 must be due to the greater steric bulk of the imine. Reaction of 222 with allylmagnesium bromide gives 223 with excellent stereoselectivity. Hydrolysis affords the free amine 224. The reactions illustrated in Schemes 32 and 33 demonstrate that 1,2-azaborolyl iron complexes can efficiently transfer chirality to B-bound organic substrates. The development of catalytic versions of these stoichiometric reactions would be a highly desirable extension of this work. 

New evidence as to the nature of the intermediates in catalytic diazoalkane decomposition comes from a comparison of olefin cyclopropanation with the electrophilic metal carbene complex (CO)jW—CHPh on one hand and Rh COAc) / NjCHCOOEt or Rh2(OAc)4 /NjCHPh on the other . For the same set of monosubstituted alkenes, a linear log-log relationship between the relative reactivities for the stoichiometric reaction with (CO)5W=CHPh and the catalytic reaction with RhjfOAc) was found (reactivity difference of 2.2 10 in the former case and 14 in the latter). No such correlation holds for di- and trisubstituted olefins, which has been attributed to steric and/or electronic differences in olefin interaction with the reactive electrophile . A linear relationship was also found between the relative reactivities of (CO)jW=CHPh and Rh2(OAc) NjCHPh. These results lead to the conclusion that the intermediates in the Rh(II)-catalyzed reaction are very similar to stable electrophilic carbenes in terms of electron demand. As far as cisjtrans stereoselectivity of cyclopropanation is concerned, no obvious relationship between Rh2(OAc) /N2CHCOOEt and Rh2(OAc),/N2CHPh was found, but the log-log plot displays an excellent linear relationship between (CO)jW=CHPh and Rh2(OAc) / N2CHPh, including mono-, 1,1-di-, 1,2-di- and trisubstituted alkenes In the phenyl-carbene transfer reactions, cis- syn-) cyclopropanes are formed preferentially, whereas trans- anti-) cyclopropanes dominate when the diazoester is involved. 

Prom a practical point of view, the application of biomimetic models to processes of synthetic, or industrial interest depends strongly on the transformation of the current stoichiometric reactions into catalytic reactions (e.g., in the phenol oxygenation reactions), the stability of the catalysts, and the introduction of stereoselectivity characteristics in the reactions, by using structurally more sophisticated and possibly chiral ligands. In addition, the biomimetic chemistry of the more complex multinuclear Cu sites, such as the trinuclear Cu sites of blue oxidases, is still in its infancy, and important contributions are expected in the next few years from the study of new and suitable model compounds. 

NMR investigation of the stoichiometric reactions of chiral amido Ru complexes, Ru(N-sulfonylated dpen)(r 6-arene) la-c, with dimethyl malo-nate 2 and P-keto ester 3 revealed that at lowered temperatures deprotonation proceeds in a stereoselective manner to provide corresponding amine complexes 4,5 and 6,7 (Scheme 2.1). 

In order to make these oxidative reactions of 1,3-dienes catalytic, several reoxidants are used. In general, a stoichiometric amount of benzoquinone is used. Furthermore, Fe-phthalocyanine complex or Co-salen complex is used to reoxidize hydroquinone to benzoquinone. Also, it was found that the reaction is faster and stereoselectivity is higher when (phenylsulflnyl)benzoquinone (383) is used owing to coordination of the sulfinyl group to Pd, Thus the reaction can be carried out using catalytic amounts of PdfOAcji and (arylsulfinyl)benzoquinone in the presence of the Fe or Co complex under an oxygen atmosphere[320]. Oxidative dicyanation of butadiene takes place to give l,4-dicyano-2-butene(384) (40%) and l,2-dicyano-3-butene (385)[32l]. 

This procedure illustrates a general method for the preparation of alkenes from the pal 1 adium(Q)-cata1yzed reaction of vinyl halides with organo-lithium compounds, which can be prepared by various methods, including direct regioselective lithiation of hydrocarbons. The method is simple and has been used to prepare a variety of alkenes stereoselectively. Similar stoichiometric organocopper reactions sometimes proceed in a nonstereoselective... 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

Intermolecular allylation of aldehydes with 1 -trialkylsilyl-1,3-dienes 22 in the presence of a stoichiometric amount of triethylsilane and a catalytic amount of Ni(cod)2 and PPI13 shows novel regio- and stereoselectivity (Scheme 6) [20-22], When a toluene solution of a 1-silyl-1,3-diene and an aldehyde is refluxed in the presence of trialkylsilane under the catalysis of Ni(cod)2 and PPh3, ( )-allylsilane (E)-23 is obtained exclusively. On the other hand, when the reaction is carried out in THF upon heating at 50 °C as... 

Abstract Significant advances have been made in the study of catalytic reductive coupling of alkenes and alkynes over the past 10 years. This work will discuss the progress made in early transition metal and lanthanide series catalytic processes using alkyl metals or silanes as the stoichiometric reductants and the progress made in the use of late transition metals for the same reactions using silanes, stannanes and borohydrides as the reductant. The mechanisms for the reactions are discussed along with stereoselective variants of the reactions. 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

If the side chain with the nucleophile is situated in the 1-position of the conjugated diene, a palladium-catalyzed spirocyclization occurs. In this case stereoselective oxa-spirocyclizations were obtained from the diene alcohols 59 and 60 (equation 23 -25)58. The reaction worked well for the formation of a tetrahydrofuran and tetrahydropyran in the spirocyclization. In the absence of chloride ions 59 gave high yields of the acetoxy oxaspirocyclic compound 61 via a 1,4-anti addition across the diene (equation 23). In the presence of stoichiometric amounts of LiCl a 1,4-syn oxychlorination took place and allylic chloride 62 was obtained (equation 24). Under chloride-free conditions, cyclohep-tadiene alcohol 60 afforded oxaspirocyclic acetate 63 (equation 25). 

In all three of the above-mentioned chiral transformations, stoichiometric amounts of enantiomerically pure compounds are required. An important development in recent years has been the introduction of more sophisticated methods that combine the elements of the first-, second-, and third-generation methods and involve the reaction of a chiral substrate with a chiral reagent. The method is particularly valuable in reactions in which two new stereogenic units are formed stereoselectively in one step (Fig. 1-30, 4). 

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