1,6-enynols

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]. 

The 36d-LAH complex has been used in the asymmetric synthesis of (3-allenic alcohols by reduction of enynols (41) as shown in eq. [14]. Although similar... 

It has been shown that the Claisen rearrangement of lithium enolates of amino acid enynol esters allows the synthesis of very sensitive y, 5-unsaturated amino acids with conjugated enyne side chains.The chelate-enolate Claisen rearrangement has also been applied to the synthesis of unsaturated polyhydroxylated amino acids, polyhydroxylated piperidines, and unsaturated peptides. ... 

Z, )-5,7-pheromone component of various Lepidoptera pheromones were synthesi2ed by cis reduction of the corresponding enynols with activated Zn. ... 

Stoichiometric enantioselective addition of lithium aluminum hydride, modified with ( — )-men-thol or sugar derivatives as chiral auxiliaries to enynols provides an entry to /Thydroxyallenes of low enantiomeric purity117 119. This method has mainly been used to establish absolute configurations of naturally occurring allenes, e.g., (—)-marasin119, and has not been optimized. 

Other additions to the triple bond of disubstituted conjugated enynols, bearing a propar-gylic alcohol moiety, were reported but proceeded in extremely low yields15,106. 

Addition of excess allylzinc bromide to the conjugated enynol 297 chemoselectively affected the triple bond and afforded a mixture of monoaddition and bis-addition products. The formation of di- and trimetallic species was unambiguously ascertained by deuteriolysis (equation 137)171. 

The intramolecular addition of hydroxyl groups to triple bonds might be utilised in the formation of furane derivatives. Enynols, having the appropriate double bond geometry, underwent ring closure and subsequent double bond isomerisation in the presence of both palladium and ruthenium catalysts to give substituted furans (3.52.),66... 

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). 

Cleavage of fi-chlorotetrahydrofurans. Sml2 cleaves either cis- or trans- -chloro-a-methyltetrahydrofurans (1) at reflux to give the (E)-unsaturated alcohol 2. This cleavage can provide (E)-dienols (4) and (E)-enynols (6). 

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>. 

Reduction of diynols to enynols. Conjugated diynols (1) are selectively reduced to (E)-enynols (2) by conversion to lithium alkynoxides with n-BuLi followed by reduction with DIB AH. 

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. 

The high diastereoselectivity obtained from the reaction of the allenylzinc bromide with isobutyraldehyde to produce the y/i-homopropargyl alcohol is rationalized by the well-known six-membered ring transition state [34]. The scope of this reaction is quite broad a-mono-a,/S-disubstituted silylated enynes as well as -mono- and ,j5-disubstituted silylated enynols are easily carbometallated using this procedure [33]. 

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