Cyclization of allenic alcohols

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... 

Silver(I) catalyzed cyclizations of allenic alcohols (202) lead to 2,5-dihydrofurans (203) (79S743), whilst another mild method for the synthesis of tetrahydrofurans is the intramolecular oxymercuration-demercuration process. Geraniol, when treated with mer-cury(II) acetate and subsequently with sodium borohydride, gave a tetrahydrofuran. 

Cyclization of allenic alcohols. Silver nitrate (1-2 equiv.) promotes cyclization of the secondary allenic alcohols 1 to give mainly t7.v-2,6-disubstituted tetrahydropyranes (2). Catalytic amounts of the salt can be used, but then the reaction is very slow. 

Dihydrofurans and Tetrahydrofurans.—Silver (i)-catalysed cyclizations of allenic alcohols lead to 2,5-dihydrofurans in moderate yields (Scheme 23). ° Dimethylsulphonium methylide reacts smoothly with o- and p-hydroxy-benzylidene ketones to yield 2,5-dihydrofurans. " Quinone methides, as inter-... 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

Cyclization of a variety of y-allenic alcohols with silver nitrate proceeds by 5-exo cyclization to form 2-alkenyltetrahydrofurans (equation 87).205c 206 Little stereoselectivity is seen in cyclizations of secondary alcohols. Cyclization by intramolecular oxypalladation/methoxycarbonylation or oxymercuration followed by transmetallation and methoxycarbonylation also showed no stereoselectivity (equation 88 and Table 24, entries 1 and 2).50 207 However, cyclization of the corresponding r-butyldimethylsilyl ether derivatives with mercury(II) trifluoroacetate followed by transmetallation/methoxycarbonylation pro-... 

N-Tosyl carbamates, such as 325, derived from allylic alcohols, undergo the Pd(II)-catalysed cyclization to furnish oxazolidinones 326 under 1 atm of CO439. Analogous Pd(II)-catalysed N-cyclization of allenic N-tosylcarbamates has generated the corresponding vinylpalladium intermediate that could be further alkylated440. 

The [(Ti-allyl)PdCl]2-catalyzed reactions of allene-aldehydes or -ketones 153 with Me3SiSnBu3 led to the cyclic 2-vinylic alcohols 155 via the formation of an aldehyde- or ketone-containing 2-trimethysilyl-2-alkenyl tin intermediate 154 (Scheme 63) [38]. In the presence of an aryl iodide, Pd2(dba)3 could catalyze the coupling cyclization of allene-aldehydes or -ketones 153 with Bu3SnSnBu3 leading to the cyclic 2-(r-arylvinyl) cyclic alcohols 156 stereoselectively with the cis isomer being the major product (Scheme 64) [39]. 

Intramolecular alkylative cyclizations of allenes with aldehydes furnish homo-allylic alcohols [206]. Tetudinariol A is synthesized by using this strategy [207]. 

In addition to the sulfur-substituted enyne-allenes depicted in Schemes 20.18-20.20, the sulfoxide 141 was prepared by treatment of the enediynyl propargylic alcohol 108 with benzenesulfenyl chloride to induce a [2,3]-sigmatropic rearrangement (Scheme 20.29) [10]. The Myers-Saito cyclization of 141 occurs at 37 °C with a half-life of only 16 min. 

Furthermore, the oxy-Cope rearrangement of allenic cycloheptane alcohol 47 (NaOEt, THF, 20 °C, 12 h, 80%) gave rise only to ring-enlarged product 48 without transannular cyclization (equation 15)29. The above transformations can be rationalized either by the fragmentation-recombination mechanism or by a concerted oxy-Cope mechanism29. 

The reaction is thermodynamically controlled and was postulated to involve an achiral, delocalized anion 15, which cyclizes to a somewhat strained 7-membered ring complex 16 capable of existing in isomeric forms. The more stable form could be hydrolyzed to the predominant ( + )-(S)-allenic alcohol 17 (Scheme 1)... 

Steiically congested cw-aziridines such as 137 were prepared from the deiivatized amino allyl alcohol precursor 136 through a palladium-catalyzed cyclization reaction <99TL1331>. This methodology has also been extended to the cyclization of amino allenes <99JOC2992>. 

When treated with catalytic amounts of acid,404 403 silver salts406"410 or mercury salts,409,410 allenic alcohols will cyclize to ethers (equations 230-253). By proper choice of reaction conditions, the yields of products obtained in these cyclizations are generally high. Interestingly, the stereoselectivity observed in equation (253) is proposed to arise from a chair conformation of the intermediate.408... 

Allenes can also act as the -participant in electrophilic heteroatom cyclizations. Reviews of electrophilic additions to allenes discuss early examples of this type of cyclization.ld le-202 Numerous examples of cyclizations of a-functionalized allenes, including carboxylic acids, phosphonates, sulfinates and alcohols, to form five-membered heterocycles (equation 84) are cited in these reviews. The silver nitrate-mediated conversion of ot-allenic alcohols to 2,5-dihydrofurans203 has recently been applied to trimethylsilyl-substituted systems.204... 

Most cyclizations of 3-allenic alcohols have produced six-membered ring products via a 6-endo process (equation 85).168 205 The exception is found with terminally unsubstituted allenes as shown in equation (86).205d The bicyclic acetal results from a 5-exo cyclization to an enol ether, which undergoes a second cyclization to form the acetal. 

Allenic alcohols with a variety of allene substitution patterns form 2-alkenyltetrahydropyrans by a 6-exo ring closure upon cyclization with silver or mercury salts (equation 91 ).209 The organosilver intermediate undergoes protiodemetallation under the reaction conditions, while the vinylmercury... 

Table 24 Effect of O-Silylation on Stereoselectivity of Cyclization of y-Allenic Alcohols (Equation 88)...

An iodine-mediated 6(0) " -exo-Trig cyclization has been used in the synthesis of (25, 4/ )-4-hydroproline from (S)-O-benzylglycidol219. Stereocontrolled 5(0) " -endo-Trig iodoetherification has provided an entry to traw.s-2.5-disubstituted tetrahydrofuran derivatives220. On treatment with iodine, trichloroimidates of primary a-allenic alcohols are converted into oxazolines with high stereoselectivity221. 

A highly regio- and stereoselective synthesis of oxepine derivatives via cyclization of bromoallenes bound with hydroxy group by a four-carbon atom tether in the presence of a palladium(O) catalyst and alcohol is developed (Equation 16). In this reaction, the bromoallenes act as an allyl dication equivalent, and the intramolecular nucleophilic attack takes place exclusively at the central carbon atom of the allene moiety <2004JA8744>. 

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