C-Silylations

The carbanions derived from thioacetals, however, are typical -synthons. Most frequently used are 1,3-dithianes and C -silylated thioethers (see p. 33f. D. Seebach, 1969, 1973 B.-T. Grobel, 1974,1977). In these derivatives the proton is removed by butyllithium in THF. 

These can be prepared in good yield by reaction of either the mono-anions of trimethylsilyl carboxylates or, preferably, the dianions of carboxylic acids with TMSCI. Acetic and propionic acids give mixtures of O- and C-silylated products. 

Acetates themselves normally give a mixture of O- and C-silylated products. However, using TBDMSC1 in the presence of HMPA (CAUTION —CANCER SUSPECT AGENT), pure ketene acetals of the type CH2=C(OR)OTBDMS can be obtained (6). 

Silyl enol ethers, 23, 77, 99-117,128 Silyl enolates, 77 Silyl peroxides, 57 Silyl triflate, 94 Silyl vinyl lithium, 11 (E)-l -Silylalk-1 -enes, 8 Silylalumimum, 8 Silylation, 94 reductive, 26 a-C-Silylation, 113 O-Silylation.99,100 / -SilyIketone, 54 non-cydic, 55 Silylmagnesium, 8 Silyloxydienes, 112 Sodium hexamethyldisilazide, 89 Sodium thiosulphate pentahydrate, 59 Stannylation, see Hydrostannylation Stannylethene, 11 (Z)-Stilbene, 70 (E)-Stilbene oxide, 70 /3-Styryltrimethylsilane, 141 Swern oxidation. 84,88... 

For group 14, C-tin-substituted phosphorus ylides have been studied in the past but less than the corresponding C-silyl ylides which, owing to their stability and reactivity, are of considerable interest. Indeed a recent review concerning the silylphosphanes with one part concerning the synthesis and applications of silylated phosphorus ylides has been published [112]. 

Some ylides 92 among them C-silylated ones have been synthesized in order to compare the stabilization influence on the carbanionic center of various C-substituents (I, SiMej, Ph3P ) [ 113]. It appears from this study that the stabilization due to the electron-withdrawing C-substituents (R or R ) is not so negligible by comparison with the hyperconjugative stabilization between the ylidic carbon and the phosphonium group [114]. This is particularly true for the iodine substituent. 

Conversion of sulfones such as 1955 into their a-sulfonyl anions by treatment with n-BuIi at -78°C in THF then addition of bis(trimethylsilyl)peroxide (BTSP) 1949 afford, via intermediates such as 1956, aldehydes or ketones such as cyclohexanone and HMDSO 7 [146]. This reaction has subsequently been applied to the synthesis of aldehydes [147]. After hthiation with -BuLi thioethers such as phenyl benzyl sulfide 1957 react with BTSP 1949 to give mixtures of the O-silyl 1958 and C-silyl 1959 products [148]. On treatment with -BuLi at -30°C the a,a-bis-(trimethylsilyl)dimethylsulfide 1960 is, hkewise, converted into its anion, which reacts with 1949 to give the a-trimethylsilyloxy sulfide 1961 and MesSiOLi 98 [149] (Scheme 12.41). 

Direct electrophilic silylation of thiadiazole 321 with bromotrimethylsilane (TMSBr) under basic conditions provides easy access to C-silyl thiadiazole 322, which can serve as a synthetic equivalent of an organometallic intermediate or a silyl-protected azole <06S 1279>. 

Recently, a method for synthesizing substituted pyridines incorporating 3-azadienynes as substrates in ruthenium-catalyzed cycloisomerizations was described <06JA4592>. This route is a two-step process that first converts readily available JV-vinyl or JV-arylamides (e.g., 26) to the corresponding C-silyl alkynyl imines (e.g., 27) and subsequent ruthenium-catalyzed protodesilylation and cycloisomerization results in the formation of the corresponding substituted pyridines (e.g., 28). 

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

Problem 17.41 Acetone reacts with lda in thf and then with trimethylsilyl chloride, (CHj),SiCI, at -78 C, to give an enolsilane. (a) Give equations for the reactions, (b) Why does O- rather than C-silylation occur ... 

Figure 10.10. Orbitals for a hydrogen atom abstraction reaction by a) alkoxyl radical from H—OR b) methyl radical from CH4 (one bond shown) (c) silyl radical from SiH4 (one bond shown).

Figure 2. DRIFT spectra of MCM-41 a) calcined, b) outer surface silylated, c) silylated in dichloromethane and d) azo dye grafted.

The synthesis and chemical reactivities of N- and C-silyl derivatives of pyrrole have been summarized (B-77MI30504). The compounds show no unusual properties. 

Dimethylalkenes.1 The readily available a-silyl esters, obtained by C-silylation of lithium ester enolates with 1, are useful precursors to trisubstituted alkenes, including 1,1-dimethylalkenes. 

In contrast to 0- and N-silylated compounds, C-silylated drugs are relatively stable against hydrolytic decomposition. For this reason, they have no importance as prodrugs so far. 

These few examples illustrate that C-silylation of drugs can also lead to interesting biological properties, which can be similar or different as compared to the parent compounds. C-silylation of bioactive organic compounds may become a routine method in the development of novel drugs. 

Phenylethynyllithium (188) reacts with silylperoxides 189a-d to give C-silylated products 190a-d or silyl ethers 191a-d or both in 48-90% overall yields (equation 79)234. The distribution of the products and the yields depend upon the steric hindrance created by the substituents attached to the silicon atom. 

---