The cyclopropylcarbinyl route to γ-silyl carbocations

Abstract

The mesylate derivative of cis-1-hydroxymethyl-2-trimethylsilylcyclopropane has been prepared, along with a number of related mesylates and triflates with substituents on the 1-position. These substrates all solvolyze in CD3CO2D to give products derived from cyclopropylcarbinyl cations that undergo further rearrangement to give 3-trimethylsilylcyclobutyl cations. These 3-trimethylsilylcyclobutyl cations are stabilized by a long-range rear lobe interaction with the γ-trimethylsilyl group. When the substituent is electron-withdrawing (CF3, CN, or CO2CH3), significant amounts of bicyclobutane products are formed. The bicyclobutanes are a result of γ-trimethylsilyl elimination from the cationic intermediate that has an unusually long calculated Si–C bond. The solvolysis chemistry of mesylate and triflate derivatives of trans-1-hydroxymethyl-2-trimethylsilylcyclopropane and 1-substituted analogs can be quite different since these substrates do not generally lead to 3-trimethylsilylcyclobutyl cations.

Fluoroalkyl‐Containing 1,2‐Disubstituted Cyclobutanes: Advanced Building Blocks for Medicinal Chemistry

“…All the compounds shown in Figure 1 demonstrate the 1,3‐substitution pattern of the fluorinated cyclobutane fragment; this is partially related to their more or less satisfactory synthetic accessibility. The known approaches to install the fluoroalkyl group onto the cyclobutane ring relied on deoxofluorination [30–33] or decarboxylative trifluoromethylation [34] of carboxylic acids, the addition of the Ruppert‐Prakash reagent or its CHF 2 ‐substituted analog to C=O and C=N bonds, [35,36] fluoride‐mediated nucleophilic substitution, [37] metal‐catalyzed C( sp 3 )−Br [38] and C( sp 3 )−H [39] trifluoromethylation, direct side‐chain C(sp 3 )−H fluorination, [40] rearrangement of fluoroalkyl‐substituted cyclopro panes, [41–43] difluoromethylation of cyclobutene with CHF 2 I, [44] and other methods. Meanwhile, the corresponding 1,2‐disubstituted fluorinated counterparts have been largely underrepresented in the literature to date [39,41,44] .…”

CF3-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

“…Further investigations by Tilley et al were conducted in order to enlarge the scope of the above-mentioned 1,3-silyl elimination of α-(trifluoromethyl) tosylate, which was restricted so far to cyclobutyl derivatives, and a variety of linear or cyclic α-(trifluoromethyl)-γ-silyl sulfonates was targeted ( Scheme 69 ) [ 163 – 164 ]. While the solvolysis was readily performed with tosylate-like leaving groups in the case of aromatic substituents being present, as in 273a – h , or in the cyclic systems 274a , b , a better leaving group, such as triflate, was generally required for alkyl derivatives 275a – d .…”

“…Very recently, Creary reported a study on the generation of CF 3 -subtituted γ-silylcarbenium ions via a cyclopropylcarbinyl rearrangement [ 164 ]. When cyclopropylcarbinylcarbenium ion 284 is generated, this species is in an equilibrium with the homoallylcarbenium and cyclobutylcarbenium ions 285 and 286 ( Scheme 71 ) [ 164 ].…”

“…Creary investigated the solvolysis of CF 3 -substituted cyclopropylcarbinyl triflate 287a and obtained a mixture of bicyclobutane 271a and unrearranged solvent-substitution product 289a in 71% and 29% yield, respectively ( Scheme 72 ) [ 164 ]. This result was in stark contrast with those obtained with Ph- and H-substituted analogues 287b and 287c because the main products of the reactions in the latter cases were cyclobutanes 290b and 290c .…”

“…Creary then considered the diastereomers of 287a – c , namely 291a – c . While 291b led to the same product 290b , the isomer 290a and unsubstituted 290c exhibited a different reactivity as they did not form the rearranged cyclobutane derivatives 290a and 290c ( Scheme 73 ) [ 164 ]. It was mentioned that for isomers 291a – c , the conformation of the corresponding cyclobutylcarbenium ions 293a – c after the rearrangement would not allow the percaudal participation of the TMS group.…”