Electrophilic trap

Scli ir 3.16. Silylciipratioci of allcyciec with (t-BiiPh Sil CiiLi-LiCN acid electrophilic trapping of the vinylciiprate reagent [69]. 

Table 5.4 Electrophile trapping of lithiated epoxides containing anion-stabilizing groups.

Florio et al. demonstrated that the lithiation/electrophile trapping of enantio-pure styrene oxide, as well as the (3-substituted styrene oxides 180 and 182, is totally stereoselective (Scheme 5.42) [66]. These results demonstrate that the intermediate benzylic anions are configurationally stable within the timescale of depro-tonation/electrophile trapping. 

Table 5.5 Lithiation-electrophile trapping of a-organyl-substi-tuted epoxides.

Pale et al. have reported that the stereoselective electrophile trapping of alkynyl-stabilized lithiated epoxides 189, generated from the parent epoxide 188 and n-BuLi, gives substituted epoxides such as 190, in good yield and de (Scheme 5.44) [67]. 

Florio and coworkers have also reported the use of oxazolinyl groups as anion-stabilizing substituents. Lithiation/electrophile trapping of oxazolinylepoxide 202 provided access to acyloxiranes 205 [72], while deprotonation/electrophile trapping of oxazolinylepoxide 206 with nitrones gave access to enantiopure a-epoxy- 3-amino acids 208 (Scheme 5.48) [73],... 

Lithiation/electrophile trapping of enantiopure epoxide 209 stereoselectively gave epoxide 211 further elaboration via a metalated epoxide gave spirocydic epoxide 212, which after treatment with acid gave epoxylactone 213 as a single dia-stereomer (Scheme 5.49) [74]. 

Electrophile trapping of simple metalated epoxides (i. e., those not possessing an anion-stabilizing group) is possible. Treatment of epoxystannane 217 with n-BuLi (1 equiv.) in the presence of TMEDA gave epoxy alcohol 218 in 77% yield after trapping with acetone (Scheme 5.51) [76], In the absence of TMEDA, the non-stabilized epoxides underwent dimerization to give mixtures of enediols. 

Hodgson and coworkers have demonstrated that the use of diamine ligands in combination with s-BuLi allows the direct deprotonation/electrophile trapping of... 

Use of LTMP as base [52] in situ with Me3SiCl allows straightforward access to a variety of synthetically useful a, 3-epoxysilanes 232 at near ambient temperature directly from (enantiopure) terminal epoxides 231 (Scheme 5.55) [81]. This reaction relies on the fact that the hindered lithium amide LTMP is compatible with Me3SiCl under the reaction conditions and that the electrophile trapping of the nonstabilized lithiated epoxide intermediate must be very rapid, since the latter are usually thermally very labile. 

Seebach and coworkers examined the deprotonation/electrophile trapping of phe-nylthioaziridine carboxylates 236 (Scheme 5.58). These thioesters were found to be more stable than their oxy-ester congeners when lithiated treatment of 236 with LDA at -78 °C, followed by trapping with Mel at -100 °C, stereoselectively afforded aziridine 237 [83]. 

Sulfonylaziridine 243 was halogenated in carbon tetrahalides in the presence of KOH as base [86] (Scheme 5.61). Although other examples of electrophile trapping of sulfonyl- and phosphonyl-stabilized metalated aziridines exist, the reactions were not stereoselective [87]. 

Reports of the generation and subsequent electrophile trapping of nonstabilized metalated aziridines appeared before those for metalated epoxides. Desulfinylation of sulfinylaziridine 250 with EtMgBr gave metalated aziridine 251, which, remarkably, could be kept at 0 °C for 1 h before quenching with D2O (Scheme 5.64). The deuterated aziridine 252 (E = D) was obtained in excellent yield, but acetaldehyde was the only other electrophile found to be trapped efficiently [90],... 

Direct deprotonation/electrophile trapping of simple aziridines is also possible. Treatment of a range of N-Bus-protected terminal aziridines 265 with LTMP in the presence ofMe3SiCl in THF at-78 °C stereospecifically gave trans-a, 3-aziridinylsi-lanes 266 (Scheme 5.67) [96]. By increasing the reaction temperature (to 0 °C) it was also possible to a-silylate a (3-disubstituted aziridine one should note that attempted silylation of the analogous epoxide did not provide any of the desired product [81],... 

Extension of these processes to provide enantio-enriched products was successfully applied after desymmetrization of the starting materials. An example is shown below (Reaction 76), where silane-mediated xanthate deoxygenation-rearrangement-electrophile trapping afforded the conversion of (+)-94 to (+)-95 in 56% yield. ... 

The synthesis of S-phosphonothiazolin-2-one 133 started with 2-bromothiazole 129. Nucleophilic displacement of the 2-bromide proceeded cleanly with hot anhydrous sodium methoxide to give 2-methoxythiazole 130. Low-temperature metalation of 130 with n-butyl lithium occurred selectively at the 5-position (76), and subsequent electrophilic trapping with diethyl chlorophosphate produced the 5-phosphonate 131. Deprotection of 131 was accomplished either stepwise with mild acid to pn uce the thiazolin-2-one intermediate 132, or directly with trimethylsilyl bromide to give the free phosphonic acid 133, which was isolated as its cyclohexylammonium salt. 

Scheme 2.26. Copper-mediated Michael addition/electrophilic trapping.

Scheme 2.201. Synthesis of c/s-bicyclo[3.3.0]octenes via domino carbolithiation/ electrocyclization/electrophile trapping.

As illustrated in the conversion of 111 to 112 below, a variety of indoles bearing chirality at C3 was accessed by O Shea and co-workers by means of a (-)-sparteine directed enantioselective carbolithiation of 2-propenyl anilines, followed by electrophilic trapping-cyclization of the lithio intermediates <06JACS10360>. 

The sequence of chiral 1,4-reduction of a fi-substituted cyclopentenone followed by electrophilic trapping of the intermediate enolate provides an efficient route to chiral 2,3-disubstituted cyclopentanones that generates two chiral centers in the process (Eq. 352)459... 

Scheme 2.38 Functionalized allenes formed by 1,4-addition of organolithium reagents to enynes and electrophilic trapping with aldehydes (111, 112) ketones (113,114), ethylene oxide (115) and carbon dioxide (116).

Scheme 2.56 Synthesis of functionalized allenes by electrophilic trapping ofthe enyne-titanium alkoxide complex 177.

Scheme 3.16. Silylcupration of alkynes with (t-BuPh2Si)2CuLi-LiCN and electrophilic trapping of the vinylcuprate reagent [69].

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