Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

Abstract

Metal-catalyzed cycloisomerizations of ene-ynes lie among the most powerful methods for the elaboration of cyclic or polycyclic organic compounds. [1] In recent years, achievements in the field of platinum- [2][3][4][5][6] and gold-catalyzed [7][8][9][10][11][12][13][14] cycloisomerizations of ene-ynes have been particularly noteworthy. As a result of their high reactivity and mild reaction conditions, gold(I) salts or complexes are currently emerging as the most promising catalysts for these reactions.[15]Whereas the gold-catalyzed cycloisomerizations of ene-ynes accommodate the presence of oxygen or nitrogen atoms in the tether, [7a-c] and enol ethers as nucleophilic partners, [7a, 9b] eneynamines [5d,e] and ene-ynol ethers [10b] have been seldom considered as substrates. Herein, we report the first examples of gold-catalyzed cycloisomerizations of 1,6-ene-ynamides that lead to substituted cyclobutanones or azabicyclic compounds, depending on the substitution pattern, and proceed with high levels of diastereoselectivity.The platinum(II)-catalyzed cycloisomerization of eneynamides has already been investigated. [5d,e] Little difference, in terms of reactivity relative to the non-heterosubstituted series, was apparent for the most simple 1,6-ene-ynamide 1, which was converted into the so-called "formal metathesis product" 2 (98 %).[16] By contrast, the platinum(II)-catalyzed cycloisomerization of the homologous 1,7-ene-ynamide 3 led to the cyclobutene intermediate 4, which was isolated in rather low yield (34 %), and the latter was therefore best hydrolyzed directly to the corresponding cyclobutanone 5 (65 %).[5d,e] Compounds 2 and 4 were assumed to originate from a cyclopropyl platinum carbene intermediate of type A (M = PtCl 2 ). [3, 4,14] The latter underwent ring expansion to the cyclobutylcation B, stabilized by the nitrogen atom, [17] and demetalation afforded the cyclobutene intermediate of type C. For 1,6-ene-ynamides such as 1, it was suggested that the double bond in the cyclobutene of type C (n = 1) remained in the more stable exo position but that this intermediate underwent electrocyclic ring opening to afford the 1,3-diene 2. However, recent mechanistic investigations suggest that the formation of 1,3-dienes, such as 2, may result from the skeletal rearrangements of the cyclopropyl metal carbenes of type A (n = 1) via intermediates of type D and/or E. [14] In the case of 1,7-ene-ynamides such as 3, the migration of the double bond to the more stable endo position took place, thus resulting in lower ring strain, and led to the cyclobutene 4. As a consequence of the platinum-catalyzed reaction pathways, any stereocenter generated in the initial stages of the cycloisomerization in the metal carbene of type A would be lost in subsequent steps (Scheme 1).The use of milder reaction conditions should enable the rate of the skeletal rearrangements of the cyclopropyl metal carbene of type A to be decreased and/or avoid the electrocyclic ring opening of the intermediate cyclobutene of type C, both of wh...

Cycloisomerization of 1,n‐Enynes: Challenging Metal‐Catalyzed Rearrangements and Mechanistic Insights

“…[168] The reactivity of eneynamides had previously been studied by Malacria and co-workers [Eq. (109)] [132] and showed a similar reactivity in the presence of platinum, albeit at a higher temperature.…”

Cycloisomerisierungen von 1,n‐Eninen: faszinierende metallkatalysierte Umlagerungen und mechanistische Einblicke

“…[168] Malacria et al [132] hatten schon früher die Reaktivität von Eninamiden in Gegenwart von Platin untersucht und eine ähnliche Reaktivität festgestellt, wenn auch bei höherer Temperatur [siehe Gl. [149,150,173] oder auf Gold(III)-Vorstufen [115,174] [Gl.…”

Synthesis of 1,2‐Amino Alcohols by Sigmatropic Rearrangements of 3‐(N‐Tosylamino)allylic Alcohol Derivatives

“…[21,22] The copper-catalyzed cross-coupling of sulfonamide 1 a with bromoalkyne 4 [23] under the conditions reported by Hsung et al [24] provided the disubstituted ynamide 5 in excellent yield (99 %). Deprotection of the alcohol (TBAF, THF) led to ynamide 6, which underwent stereoselective hydroalumination with Red-Al to provide the (E)-3-(N-tosylamino)allylic alcohol 3 a (68 %, two steps from 5).…”