Gold‐Catalyzed Oxidative Cyclization of 1,5‐Enynes Using External Oxidants

Abstract

Pd-catalyzed oxidative cyclizations of 1,6-enynes have found useful applications in organic synthesis, [1] but such reactions with Au and Pt catalysis remain largely unexplored.[2] Goldcatalyzed cycloisomerizations of 1,5-and 1,6-enynes provide uncommon and useful carbocyclic frameworks. [3] In the presence of organic oxidants, most enynes fail to produce oxidative cyclization products because oxidations of hypothetical gold-carbenoid intermediates are difficult. [4,5] Herein, we report two new oxidative cyclizations of 1,5-enynes via 5-endo-dig and 5-exo-dig cyclizations, respectively; both reactions are implemented with Au I and 8-methylquinoline Noxide. The success of such reactions relies on the prior oxidations of enyne [6] form a-carbonyl carbenoids A and B, followed by their intramolecular cyclizations (Scheme 1). Terminal alkynes favor the oxidation at the C2 alkynyl carbon atom and aminoalkynes prefer the C1 carbon atom. Table 1 shows the oxidative cyclization of 2-aminoalkynylstyrene 1 a [7] over commonly used Au I and Pt II catalysts (5 mol %). We employed 8-methylquinoline N-oxide, which exhibited greater catalytic activity than diphenylsulfoxide and other pyridine-based oxides. [8][9][10] Treatment of a solution of 1,5-enyne species 1 a ( We prepared various 1,5-enynes 1 b-l (Table 2) bearing an aminoalkynyl substituent to assess the generality of this oxidative cyclization. Entries 1-5 in Table 2 show the applicability of this catalysis to enynes 1 b-1 f bearing varied electron-withdrawing amino groups including R 2 = Ms and Ts (Ms = methansulfonyl, Ts = toluene-4-sulfonyl), R 3 = Me, nBu, and phenyl to produce 3-carbonyl-1H-indene products 2 b-2 f in good yields (78-92 %). Similar to its analogue 1 a, propan-4-sultam species 1 g was compatible with this catalysis,

Gold‐Catalyzed Enantioselective Annulations

“…After some optimization of reaction conditions, the desired products, bicyclic cyclopropanes 44 , were indeed obtained in moderate to good yields with up to 94 % ee when bis‐tributylsilyl‐substituted ligand L3 was used (Scheme ). Both Liu and L. Zhang viewed the α‐oxo gold carbene 36 as the real intermediate involved in the cyclopropanation process, which was very different from our hypothesis. Amazingly, L. Zhang developed a tricoordinated gold carbene 36 by exploiting the affinity of both the P and N atoms of L3 .…”

Metal‐Free Cyclization of ortho‐Nitroaryl Ynamides and Ynamines towards Spiropseudoindoxyls

“…[1] Steady improvements in their synthesis and commercial availability [2] have made several of these building blocks available to the chemical community.T he electron-donating nature of the ynamide nitrogen atom polarizes the triple bond;t his feature can be employed to obtain high degrees of reactivity and regioselectivity,and has enabled avariety of impressive transformations. [4] In contrast to the surge of interest in ynamides,r eactions with ynamines are less frequent because these compounds are more sensitive and difficult to handle. These reactions afford a-oxo amide carbenoids (or related stabilized cations), which can be used in the synthesis of various heterocycles.…”

[3,3]-Sigmatropic Rearrangement versus Carbene Formation in Gold-Catalyzed Transformations of Alkynyl Aryl Sulfoxides: Mechanistic Studies and Expanded Reaction Scope

“…16 To our delight, this strategy has also been adopted by other researchers in the development of versatile synthetic methods. 18 …”