Alkynic alcohols cyclization

Several ways to suppress the 2-oxonium-[3,3]-rearrangements might be envisioned. Apart from the introduction of a bulky substituent R at the aldehyde (Scheme 23) a similar steric repulsion between R and R might also be observed upon introduction of a bulky auxiliary at R. A proof-of-principle for this concept was observed upon by using of a trimethylsilyl group as substituent R in the alkyne moiety (Scheme 25, R = TMS). This improvement provided an efficient access to polysubstituted dihydropyrans via a silyl alkyne-Prins cyclization. Ab initio theoretical calculations support the proposed mechanism. Moreover, the use of enantiomerically enriched secondary homopropargylic alcohols yielded the corresponding oxa-cycles with similar enantiomeric purity [38]. 

Scheme 25 Silyl alkyne-Prins cyclization of secondary homopropargylic alcohols and aldehydes using FeXs as a promoter...

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). 

Several cyclofunctionalization reactions of alkynic alcohols are synthetically useful. Metal ion-promoted cyclofunctionalization of ris-2-propargylcyclopentanol systems proceeds by the 5-exo mode (equation 77 and Table 23).197 Protiodemetallation or reductive demetallation provides the cyclic enol ether in high yields. This method has been used by Noyori in the synthesis of prostacyclin (PGh).197b,197c Reactions with catalytic amounts of mercury(II) or palladium(II) salts gave the endocyclic enol ether as the major product.197 -198 A related cyclization with Ag2C03 has been reported by Chuche.191 Schwartz... 

Cyclization of Divinyl Ketones from Alkynic Alcohols... 

Moving one step further back in the synthetic sequence towards cyclopentenoftes identifies the alkynic alcohols as viable precursors. Since the subsequent dehydration-hydration-cyclization steps are all acid-... 

Dimethyl acetylenedicarboxylate (DMAD) (125) is a very special alkyne and undergoes interesting cyclotrimerization and co-cyclization reactions of its own using the poorly soluble polymeric palladacyclopentadiene complex (TCPC) 75 and its diazadiene stabilized complex 123 as precursors of Pd(0) catalysts, Cyclotrimerization of DMAD is catalyzed by 123[60], In addition to the hexa-substituted benzene 126, the cyclooctatetraene derivative 127 was obtained by the co-cyclization of trimethylsilylpropargyl alcohol with an excess of DMAD (125)[6l], Co-cyclization is possible with various alkenes. The naphthalene-tetracarboxylate 129 was obtained by the reaction of methoxyallene (128) with an excess of DMAD using the catalyst 123[62],... 

In the case of terminal alkynes having oxygenated functions in the linear chain (Scheme 10, route D), Martin, Padron, and coworkers found that homopropargylic alcohols reacted properly, yielding 2-substituted dihydropyrans as sole products, probably via a Prins-type cyclization. This cyclization provides a new approach toward 2-alkyM-halo-5,6-dihydro-2//-pyrans through a concomitant C-C and C-O bond formation (Scheme 21) [35]. 

Since cumulenes and alkynes are often easily interconvertible, many syntheses discussed above have allenic counterparts, especially base-catalyzed cyclizations of allenic alcohols.77 And, of course, several of the alkyne-based syntheses may well have allenic intermediates. There are, however, a few syntheses based specifically upon allene chemistry. In an important one, due to Stirling and his collaborators,78 an allenic sulfonium salt reacts with an enolate anion. Scheme 12 sketches the main features yields as high as 86% are recorded. Methoxyallene is easily metallated by butyllithium and so converted into an allenic epoxide that can be isomerized by fe/T-butoxide into a furan (Scheme 13) or an exocyclic equivalent similar to 15 clearly this method is particularly suited to the preparation of 3-methoxyfuran... 

The very first example of the catalytic reductive cyclization of an acetylenic aldehyde involves the use of a late transition metal catalyst. Exposure of alkynal 78a to a catalytic amount of Rh2Co2(CO)12 in the presence of Et3SiH induces highly stereoselective hydrosilylation-cyclization to provide the allylic alcohol 78b.1 8 This rhodium-based catalytic system is applicable to the cyclization of terminal alkynes to form five-membered rings, thus complementing the scope of the titanocene-catalyzed reaction (Scheme 54). 

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). 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

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... 

The final cyclization manifold has been realized with a different ruthenium catalyst (Scheme 22). The cationic [Cp Ru(MeCN)3]PF6 induces exclusive endo-dig cyclization of both homopropargylic and bis-homopropargylic alcohols.29 73 The clean reaction to form a seven-membered ring is noteworthy for several reasons intramolecular exo-dig cyclization with bis-homopropargylic alcohols is not well established, the platinum-catalyzed case has been reported to be problematic,80 and the selectivity for seven-membered ring formation over the exo-dig cyclization to form a six-membered ring is likely not thermodynamic. The endo-dig cyclization manifold was thus significant evidence that a re-examination of alkyne hydrosilylation mechanisms is necessary (see Section 10.17.2). 

Silyl propargyl alcohols, XC=CSiMe2R [X=RiCH(OH)CHR2CH(SPh)], can undergo palladium(II)-catalysed cyclization to give 2,3-dihydrofurans, or alkyne... 

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