Enynols cyclization

The reaction of a bis-alkynic alcohol (103) with aqueous dimethylamine gives dimethyl-aminofuran (104) (74IZV206). trans-Enynols cyclize presumably through a cis intermediate with base (75RTC70) or mercury(II) sulfate, a method used for the synthesis of the terpenoid bilabone (105) (69JOC857). 

A large number of examples of the intramolecular hydroalkoxylation reaction of alkynes bearing pendant alcohols have been reported. In the reactions of enynols, the cyclization process has typically been accompanied by isomerization of the resulting enol ethers to give rise to furan or pyran products. These processes have been achieved using Pd(ll),294-297 Ru(n),298,299 Au(i),300 Au(m)286,300,301 Ir(i)302 Ir(m) 303 and Ag(i) 304 catalysts. Some examples are shown in Equations (83)-(87). 

The cyclization of alkenols can also occur through an interesting relay mechanism (Equation (125)). Under AuC13 catalysis, the alkyne of an enynol is first activated to promote a cationic G-G bond-forming cyclization with the alkene. The G-O bond-forming ring closure then occurs via capture of the carbocation by the alcohol.451... 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

Z)-Enynols can also be employed as substrates when ruthenium or iridium catalysts are used <2006ASC1671>. Furan-2-acetic esters are obtained by a Pd(n)-catalyzed oxidative cyclization-alkoxycarbonylation of (Z)-enynols <1999JOC7693>. In analogy, 2-furan-2-ylacetamides are obtained in an aminocarbonylation with secondary amines (Equation 22) <2006S4247>. 

Electrophilic cyclization of a wide variety of (Z)-enynols affords substituted (Z)-5-(l-iodoylidene)-2,5-dihydrofur-ans with high regio- and stereoselectivity under mild reaction conditions. To access the cyclization precursors 27, a zirconium-mediated cross-coupling reaction of three different components involving an alkyne, a ketone, an alkynyl bromide in a one-pot procedure has been developed (Scheme 34) <2005JOC6999>. 

A interesting variation on this theme employing the isomeric enynol acetates (Scheme 24) has been developed by Rautenstrauch. The cyclizations are induced by a Pd" catalyst in warm acetonitrile. The proposed mechanism is intriguing. Reaction is initiated by an anchimerically assisted palladation to (35) followed by opening the dioxolenium ion to a pentadienylic cation (36). The closure of (36) is analogous to the silicon-directed Nazarov cyclization in the ejection of the Pd" electrofuge from (37). Both secondary and tertiary acetates can be employed as well as both acyclic and monocyclic systems. 

Another example concerning furan synthesis by gold-catalyzed cyclization was also reported. Reaction of (Z)-enynols using AuClj furnish fully substituted furans in high yields under mild reaction conditions <050L5409>. 

Interesting results have been obtained with (r[ -arene)(rtkpyi idine)RuCl2 catalysts anchored on an inorganic matrix. Preliminary results from Se kin s laboratory demonstrated that such solid-supported complexes were easily prepared and displayed high catalytic activities towards the intramolecular cyclization of enynols to furans [57]. 

Building on the earlier work of Hashmi [15], Liu has reported the gold-catalyzed cycloisomerization and oxidative cyclization of (Z)-enynols [16,17]. As an example of the former transformation, treatment of the tetraphenyl enynol 7 with a catalytic amount of AuCh in dichloromethane at room temperature led to isolation of... 

Rautenstrauch reported another mechanistically intriguing example. Treatment of enynol acetate 111 with a palladium(II) catalyst in warm acetonitrile resulted in the formation of cyclopentenone 115. The proposed mechanism involves generation of divinyl cationic species 113, followed by electrocyclization, and elimination of the palladium(ll) electrofuge in a manner comparable to the silicon-directed Nazarov cyclization (see Section 3.4.5.1). 

Analogous cleavage of a C=C triple bond has been found in the gold-catalyzed cyclization of (Z)-enynol 157 under an oxygen atmosphere (Scheme 7.54) [73]. Butenolide 159 was obtained by way of the cyclic alkenyl ether 158. 

---