Ester Formation via Symbiotic Activation Utilizing Trichloroacetimidate Electrophiles

Abstract

Trichloroacetimidates are useful reagents for the synthesis of esters under mild conditions that do not require an exogenous promoter. These conditions avoid the undesired decomposition of substrates with sensitive functional groups that are often observed with the use of strong Lewis or Brønsted acids. With heating, these reactions have been extended to benzyl esters without electron donating groups. These inexpensive and convenient methods should find application in the formation of esters in complex substrates.

Esterifications with 2-(Trimethylsilyl)ethyl 2,2,2-Trichloroacetimidate

“…These poor yields were attributed to decomposition of the imidate in the presence of the strong acid catalysts. Esterification under promoter free conditions [32][33][34] was then explored by heating carboxylic acid 1 and imidate 2 in refluxing toluene for 24 h (entry 7). These conditions gave complete conversion to the TMSE ester, but the ester product was difficult to separate from the excess imidate.…”

“…Recently, we have been involved in a number of studies evaluating the promoter free reactivity of trichloroacetimidate electrophiles with nitrogen [26,27], sulfur [28], and oxygen [29] nucleophiles. Carboxylic acids have been noted to be alkylated under promoterfree conditions via symbiotic activation by trichloroacetimidates that are precursors to stabilized carbocations, including the 2-phenylisopropyl [30,31], 4-methoxybenzyl [32], diphenylmethyl [33], and tert-butyl imidates [34]. Given that trichloroacetimidates are simple to prepare from inexpensive starting materials and that the esterifications often proceed under mild conditions without the need for an exogenous promoter or catalyst, the formation of TMSE esters using this chemistry was investigated.…”

Dialkylation of Indoles with Trichloroacetimidates to Access 3,3-Disubstituted Indolenines

“…Our recent studies on promoter free substitution reactions with trichloroacetimidate electrophiles [68,69,70,71,72,73,74] led us to speculate that imidates may be reactive enough to participate in indole dialkylation without the need for a Lewis acid catalyst. Heating 2-methyl indole 14 and allyl trichloroacetimidate 11 in refluxing 1,2-dichloroethane (DCE) for 24 h showed no trace of alkylation product, however, so the use of TMSOTf as the Lewis acid was then investigated (Table 1).…”

Esterifications with 2-(Trimethylsilyl)ethyl 2,2,2- Trichloroacetimidate

“…Carboxylic acids have been noted to be alkylated under promoter free conditions via symbiotic activation by trichloroacetimidates that are precursors to stabilized carbocations, including the 2phenylisopropyl, 14 4-methoxybenzyl, 15 diphenylmethyl 16 and tert-butyl imidates. 17 Given that trichloroacetimidates are simple to prepare form inexpensive starting materials and that the esterifications often proceed under mild conditions without the need for an exogenous promoter or catalyst, the formation of TMSE esters using this chemistry was investigated. Use of the previously unknown trimethylsilylethyl trichloroacetimidate 2, which may be a precursor to a bsilyl stabilized carbocation that can be trapped with an carboxylic acid, would provide a mild method for installing a TMSE ester with trichloroacetamide 4 as the sole by product, which is easily removed by washing with aqueous sodium hydroxide.…”

“…These poor yields were attributed to decomposition of the imidate in the presence of the strong acid catalysts. Esterification under promoter free conditions [15][16][17] was then explored by heating carboxylic acid 1 and imidate 2 in refluxing toluene for 24 hours (entry 7). These conditions gave complete conversion to the TMSE ester, but the ester product was difficult to separate from the excess imidate.…”