Subject unsymmetrical, synthesis

Because the Williamson synthesis is an S 2 reaction, it is subject to all the usual constraints, as discussed in Section 11.2. Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates. Unsymmetrical ethers should therefore be synthesized by reaction between the more hindered alkoxide partner and less hindered halide partner rather than vice versa. For example, terf-butyl methyl ether, a substance used in the 1990s as an octane booster in gasoline, is best prepared by reaction of tert-butoxide ion. with iodomethane rather than by reaction of methoxide ion with 2-chloro-2-methylpropane. 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

In the synthesis of the 1 1 cobalt complex 17 by the nitrite method, a mixture of CoS04-7 H20 and NaN02 in water and the dye formed by acid coupling of diazotized 2-amino-4,6-dinitrophenol with 2-phenylaminonaphthalene-4 -sulfonic acid is subjected to dropwise addition of dimethylformamide. Metallization commences immediately and is complete within 2 h. The 1 1 cobalt complex 17 is precipitated by addition of NaCl and isolated. It is a suitable intermediate for producing unsymmetrical 1 2 cobalt complex dyes such as 18. 

Chiral sulfoxides are useful intermediates in asymmetric synthesis. A number of methods for their preparation were developed in the last decade. An interesting displacement of dimethylphosphonylmethyl moiety, a carbon leaving group, from sulfur by Grignard reagents was used to obtain enantiomerically purep-tolyl sulfoxides.3 4 Optically pure methyl 4-bromophenyl sulfinate was subjected to a one-pot sequence yielding unsymmetrical dialkyl sulfoxides in 60-97% yield and >98% ee. A simple one-pot synthesis of chiral sulfoxides from norephedrine-derived... 

The synthesis of disilanes via silylmetallic reagents has been the subject of several recent reviews (4, 5, 14). Since the silylmetallic reagents are prepared by the reaction of metals with triorganohalosilanes ( direct preparation) or hexaorganodisilanes, the reagents are chiefly used for the synthesis of unsymmetrical rather than symmetrical disilanes. 

The well-known synthesis of enamino-thioketones (21) using the reaction of 1,2-dithiolium salts with primary or secondary amines has been the subject of renewed investigation. " Duguay and Quiniou observed that the action of p-methylaniline on unsymmetrical 3,5-diaryI-l,2-dithiolium... 

Regioselective techniques were developed to direct the cyclization of unsymmetrical esters. An interesting example of this aspect of the Dieckmann condensation is the synthesis of ip-methylcarbapenems by Tanabe and co-workers, ip-methylcarbapenems is a structure that exists in potent and broad antibacterial compounds, such as meropenem and biapenem, which renders it synthetically interesting for the synthesis of some close analogues 30a-d. Thioesters 29 was subjected to cyclization under dehydration type Ti-Dieckmann condensation conditions 3.0 equivalents of the TiCU and 3.3 equivalents of the base BusN were used to give the vinyl... 

Carbon-nitrogen bond formation is an important subject in the organic synthesis [301], and hydroamination is an atom-efficient process for the generation of amines and imines from olefins, allenes, and alkynes. Titanium-mediated hydroamination was among the most useful protocols thus far developed for this reaction. By using unsymmetrical olefins and alkynes, the addition of HNR2 can in principle lead to two isomeric products, where the isomeric ratio is usually dependent on the type of titanium catalyst used. 

Because the Williamson synthesis is an 5 2 reaction, it is subject to all the usual constraints, as discussed in Section 12.7. Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates. Unsymmetrical ethers should therefore he synthesized by reaction... 

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