Gold -catalyzed enyne cyclization

Representative procedure for the gold-catalyzed tandem cyclization/pinacol rarrangement of 3-silyloxy-l,5-enynes. 3a,4,5.6,7,7a-Hexahydro-l-phenyl-3H-indene-3a-carbaldehyde ° ... 

Scheme 16.9 Ligand effects on selectivity in a gold(l)-catalyzed enyne cyclization.

Intramolecular additions of alcohols or amines to olefins are recognized as useful methods to provide heterocyclic compounds. Kozmin and Zhang have achieved a gold-catalyzed synthesis of heterobicyclic alkenes by double cyclization of alcohols or sulfonamides which have a 1,5-enyne moiety [175]. As a typical example, unsaturated alcohol (95) is smoothly converted to 6-oxabicyclo[3.2.1]octane (96) in 90% yield using a 5 mol% of AuCls catalyst (Scheme 18.34). Cyclic ethers are also available from homopropargylic ethers with pendant alcohols through gold-catalyzed... 

Scheme 1.14 Selected products in the gold-catalyzed cyclization of 1,6-enynes...

Gold-catalyzed cyclization of 1,5-enynes allows the synthesis of a wide variety of synthetically useful products (Scheme 1.22) [24, 160]. The mechanism of 1,5-enynes resembles the one of 1,6-enynes, cyclizing through an endocycUc pathway. 

Gold(I)-catalyzed cyclization of 1,8-enynes gives cyclobutene compounds as the main product (Scheme 1.25) [145, 197]. These intermediates can also to give isomerization or fragmentation products after prolonged reaction times or in the presence of traces of acids. Furthermore, cyclobutene compounds can also be synthesized from certain 1,6- and 1,7-enynes [15]. The formation of cyclobutene compounds by gold-catalyzed cycloisomerization of l,n-enynes will be discussed in Chap. 2. 

In 2010, Malacria and coworkers developed a novel Au-catalyzed cyclization of 1,6-enyne 9, furnishing allene-substituted tetrahydrofuran 11 in excellent yield. The proposed mechanism involves an initial enyne cyclization to generate the cationic gold-vinyl complex 10 and subsequent unexpected [l,5]-hydride shift. Deuteration experiments support the [l,5]-hydride shift and rule out the inter-molecular scrambling. This cascade reaction is unusual because the cyclization precedes followed by an uncommon [l,5]-hydride shift (Scheme 12.5) [9]. 

Fig. 6.21 Gold-catalyzed 1,6-enyne cyclization and Au(I)Cl complex containing the axially chiral phosphinine ligand 10...

Hypothetical (carbene)gold(i) structures of intermediates and reaction coordinates have been calculated (B3LYP/ 6-31G and LAN2DZ levels) for (H3P)Au+-catalyzed cyclization reactions of terminal enynes. The endocyclic skeletal rearrangement reactions were found to proceed exclusively via cyclopropylcarbene complexes.240... 

In a recent report, Toste and Shen developed a gold(I)-catalyzed cyclization of alkynes using silyl ketene amides that, by means of prior hydrolysis, provided 1,6-enyne (285) or 1,5-enyne systems (287) activated for the intramolecular cycloisomerization [160]. 

Yet the first examples of cyclization of 1,5-enynes with gold were disclosed by the group of Arcadi in the context of a new synthesis of pyridines (equation 48). The cyclization of propargyl enamines catalyzed by sodium tetrachloroaurate gives substituted pyridines in a general way. The enamines were formed in situ from propargylamine and the corresponding ketone. 

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