Gold enyne cyclizations

It is important to note in an overview of this chemistry that the formation of most of the products can be mechanistically explained as proceeding via cyclopropyl gold carbene intermediates. The involvement of these species has been previously proposed in enyne cyclizations with other metals and their structures have been later determined by calculations. ... 

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

The gold-catalysed cyclization/oxidative 3+2-cycloadditions of 1,5-enynes (57) with nitrosobenzene produced substituted isoxazoles (59) with high stereocontrol. The nitrosobenzene also acts as an oxidizing agent in this reaction. Alkenylgold carbocations (58) are important intermediates in this reaction sequence (Scheme 16). ... 

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. 

In order to study the intramolecular gold(I)-cyclization of 1,6-enynes bearing a carbonyl group at the alkyne moiety, enyne II-22a was synthesized via ruthe-nium(II)-catalyzed 1,4-addition of the terminal alkyne II-26a to methyl vinyl ketone with a 78 % yield (Scheme 3.14) [16]. 

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]. 

Selective activation of alkyne functions of enynes to give products either of alkoxy-cyclization or of exo- and endo-skeletal rearrangement can be achieved by using alkynophilic cationic gold(I) complexes. The endocyclic cyclization catalysed by gold(I) proceeds via a mechanism different from those known for Pd(II), Hg(II), or Rh(I) catalysts.118... 

For 1,6-enynes, the initial cyclopropyl gold carbene formed in the 5-exo-dig cyclization (equation 37) evolves to form... 

A remarkable cyclization of a 1,9-enyne (equation 43) to form a 10-membered ring has been disclosed. The aromatic ring may play a role in the cyclization, but still this result shows that formation of large rings from l,n-enynes (n > 7) by using gold chemistry is possible. Cyclizations of 1,8-enynes that probably proceed by a different mechanism have also been reported. ... 

The formation of these products can be rationalized as shown in equation (46). Thus, upon complexation of Au(I) to the aUcyne in the reacting enyne, an endo cyclization occurs to form a cyclopropyl gold carbene, which can be trapped by a nucleophile. However, the lack of stereospecificity observed in some of these reactions, suggests the formation of open six-membered ring cations as intermediates, which can be intercepted by an O-Boc group.3-Hydroxy-1,5-allenynes react similarly with Pt(II) catalysts. ... 

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. 

A synthesis of cyclopentenones somewhat related to those shown earlier was found from conjugated 1,3-enynes (equation 19) Cyclopentenones are obtained by the hydrolysis of the enol acetates. This transformation involves a 1,3-migration of the acetate to form pentadienyl cation and the formation of the gold carbene after a Nazarov-type cyclization. DFT calculations support this mechanism and provide interesting insight into the mechanism of the final stages of the process. 

Electrophilic Au(I) complexes or their halide AuX analogoues typically cyclize enynes (I, Scheme 58) (475) by a 5-exo-dig pathway to give a variety of cycloisomerization and addition derivatives. The mechanism is proposed to involve formation of a cyclopropyl gold-carbene intermediate... 

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