Rearrangement of Benzylic Trichloroacetimidates to Benzylic Trichloroacetamides

Abstract

The rearrangement of allylic trichloroacetimidates is a well-known transformation, but the corresponding rearrangement of benzylic trichloroacetimidates has not been explored as a method for the synthesis of benzylic amines. Conditions that provide the trichloroacetamide product from a benzylic trichloroacetimidate in high yield have been developed. Methods were also investigated to transform the trichloroacetamide product directly into the corresponding amine, carbamate and urea. A cationic mechanism for the rearrangement is implicated by the available data.

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

“…Allyl-2,2,2-trichloroacetimidate 11 [78], 1-(1-imino-2,2,2-trichloroethoxy)-3-phenyl-2(E)-propene 17 [79], propargyl-2,2,2-trichloroacetimidate 18 [70], (4-methoxyphenyl)methyl-2,2,2-trichloroacetimidate 19 [69], benzyl-2,2,2-trichloroacetimidate 20 [78], (4-chloro)methyl-2,2,2-trichloroacetimidate 21 [80], (4-trifluoromethyl)methyl-2,2,2-trichloroacetimidate 22 [66], and (4-nitrophenyl)methyl-2,2,2-trichloroacetimidate 23 [81] were synthesized as previously reported.…”

“…2-Methyl-3,3-bis[(p-nitrophenyl)methyl]-3H-indole ( 15p ). Synthesized by general procedure from 2-methylindole 14a and imidate 23 [81], purified using silica gel chromatography (50% EA/50% hexanes). Yellow oil (0.29 g, 63%); TLC Rf = 0.50 (10% EA/90% DCM); IR (ATR) 3076, 1728, 1577, 1451, 920, 825 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.90 (d, J = 8.8 Hz, 4H), 7.31–7.20 (m, 4H), 6.88 (d, J = 8.4 Hz, 4H), 3.48 (d, J = 13.6 Hz, 2H), 3.26 (d, J = 13.6 Hz, 2H), 2.44 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 182.0, 154.9, 147.0, 142.6, 138.7, 129.9, 129.0, 125.3, 123.1, 123.0, 120.6, 63.6, 41.9, 17.2; HRMS (ESI+) m/z calcd for C 23 H 19 N 3 O 4 [M + H] + : 402.1448, found: 402.1451.…”

Synthesis of 1,1′-Diarylethanes and Related Systems by Displacement of Trichloroacetimidates with Trimethylaluminum

“…Imidates 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6j, 6l, 6m, 6n, 6o, 6p, 6q, 6r, 6s, 6t, 6w, 6x, 6y, 6z, 6aa, 9 and 15 were synthesized from the corresponding alcohols using the general procedure. Imidates 6a, 1c 6i, 24 6k, 33 6u, 34 and 6v, 35 were synthesized according to literature protocols.…”

“…This product has recently been observed to occur when trichloroacetimidate 6a is treated with a Lewis acid. 24 A number of other Lewis acids were then screened for their ability to facilitate the substitution reaction (entries 11–15) at the expense of the rearrangement. From these results aluminum trichloride emerged as the most promising promoter, providing the desired product 7a in a 91% yield (entry 11).…”

“…Omission of the trimethylaluminum was also explored, with mainly rearrangement of the imidate to the acetamide being observed under these conditions (entry 16), as has been described previously. 24…”