Acid‐Catalyzed [3,3]‐Sigmatropic Rearrangements of N‐Propargylanilines
Authors: Barmettler Peter , Hansen Hans‐Jürgen 
Published: December 2004

The acid‐catalyzed rearrangement of N‐(1′,1′‐dimethylprop‐2′‐ynyl)‐, N‐(1′‐methylprop‐2′‐ynyl)‐, and N‐(1′‐arylprop‐2′‐ynyl)‐2,6‐, 2,4,6‐, 2,3,5,6‐, and 2,3,4,5,6‐substituted anilines in mixtures of 1N aqueous H2SO4 and ROH such as EtOH, PrOH, BuOH etc., or in CDCl3 or CCl4 in the presence of 4 to 9 mol‐equiv. trifluoroacetic acid (TFA)has been investigated (cf. Scheme 12‐25 and Tables 6 and 7). The rearrangement of N‐(3′‐X‐1′,1′‐dimethyl‐prop‐2′‐ynyl)‐2,6‐ and 2,4,6‐trimethylanilines (X = Cl, Br, I) in CDCl3/TFA occurs already at 20° with τ1/2 of ca. 1 to 5 h to yield the corresponding 6‐(1‐X‐3′‐methylbuta‐1,2′‐dienyl)‐2,6‐dimethyl‐ or 2,4,6‐trimethylcyclohexa‐2,4‐dien‐1‐iminium ions (cf. Scheme 13 and Footnotes 26 and 34) When the 4 position is not substituted, a consecutive [3,3]‐sigmatropic rearrangement takes place to yield 2,6‐dimethyl‐4‐(3′‐X‐1′,1′‐dimethylprop‐2′‐ynyl)anilines (cf. Footnotes 26 and 34). A comparable behavior is exhibited by N‐(3′‐chloro‐1′‐phenylprop‐2′‐ynyl)‐2,6‐dimethylaniline (45., cf. Table 7). The acid‐catalyzed rearrangement of the anilines with a Cl substituent at C(3′) in 1N aqueous H2SO4/ROH at 85‐95°, in addition, leads to the formation of 7‐chlorotricyclo[3.2.1.02,7]oct‐3‐en‐8‐ones as the result of an intramolecular Diels‐Alder reaction of the primarily formed iminium ions followed by hydrolysis of the iminium function (or vice versa; cf. Schemes 13,23, and 25 as well as Table 7). When there is no X substituent at C(1′) of the iminium‐ion intermediate, a [1,2]‐sigmatropic shift of the allenyl moiety at C(6) occurs in competition to the [3,3]‐sigmatropic rearrangement to yield the corresponding 3‐allenyl‐substituted anilines (cf. Schemes 12,14–18, and 20 as well as Tables 6 and 7). The rearrangement of (−)−(S)‐N‐(1′‐phenylprop‐2′‐ynyl)‐2,6‐dimethylaniline ((−)‐38; cf. Table 7) in a mixture of 1N H2SO4/PrOH at 86° leads to the formation of (−)‐(R)‐3‐(3′‐phenylpropa‐1′,2′‐dienyl)‐2,6‐dimethylaniline ((−)‐91), (+)‐(E)‐ and (−)‐(Z)‐6‐benzylidene‐1,5‐dimethyltricyclo[3.2.1.02′7]oct‐3‐en‐8‐one ((+)‐(E)‐ and (−)‐(Z)‐92, respectively), and (−)‐(S)‐2,6‐dimethyl‐4‐( 1′‐phenylprop‐2′‐ynyl)aniline((−)‐93). Recovered starting material (10%) showed a loss of 18% of its original optical purity. On the other hand, (+)‐(E)‐ and (−)‐(Z)‐92 showed the same optical purity as (minus;)‐38, as expected for intramolecular concerted processes. The CD of (+)‐(E)‐ and (−)‐(Z)‐92 clearly showed that their tricyclic skeletons possess enantiomorphic structures (cf. Fig. 1). Similar results were obtained from the acid‐catalyzed rearrangement of (−)‐(S)‐N‐(3′‐chloro‐1′phenylprop‐2′‐ynyl)‐2,6‐dimethylaniline ((−)‐45; cf. Table 7). The recovered starting material exhibited in this case a loss of 48% of its original optical purity, showing that the Cl substituent favors the heterolytic cleavage of the N–C(1′) bond in (−)‐45. A still higher degree (78%) of loss of optical activity of the starting aniline was observed in the acid‐catalyzed rearrangement of (−)‐(S)‐2,6‐dimethyl‐N‐[1′‐(p‐tolyl)prop‐2′‐ynyl]aniline ((−)‐42; cf. Scheme 25). N‐[1′‐(p‐anisyl)prop‐2‐ynyl]‐2,4,6‐trimethylaniline(43; cf. Scheme 25) underwent no acid‐catalyzed [3,3]‐sigmatropic rearrangement at all. The acid‐catalyzed rearrangement of N‐(1′,1′‐dimethylprop‐2′‐ynyl)aniline (25; cf. Scheme 10) in 1N H2SO4/BuOH at 100° led to no product formation due to the sensitivity of the expected product 53 against the reaction conditions. On the other hand, the acid‐catalyzed rearrangement of the corresponding 3′‐Cl derivative at 130° in aqueous H2SO4 in ethylene glycol led to the formation of 1,2,3,4‐tetrahydro‐2,2‐dimethylquinolin‐4‐on (54; cf. Scheme 10), the hydrolysis product of the expected 4‐chloro‐1,2‐dihydro‐2,2‐dimethylquinoline (56). Similarly, the acid‐catalyzed rearrangement of N‐(3′‐bromo‐1′‐methylprop‐2′‐ynyl)‐2,6‐diisopropylaniline (37; cf. Scheme 21) yielded, by loss of one i‐Pr group, 1,2,3,4‐tetrahydro‐8‐isopropyl‐2‐methylquinolin‐4‐one (59).