Cycloaddition of propargylic alcohols

Scheme 7.28 Cycloaddition of propargylic alcohols with phenol and naphthol derivatives.

The acid catalyzed cycloaddition of propargylic alcohols with phenols gives a mixture of 2H- and 477-chromenes <2001SC439>. The thiolate-bridged diruthenium complex 101 can effectively mediate the cycloaddition of aryl propargylic alcohols with phenols or naphthols to afford 4-aryl-4//-chromenes (Equations 57 and 58) <2002JA7900>. 

Michael addition of 1 to dimethyl acetylene dicarboxylate in the presence of sodium methoxide, potassium fluoride, or aluminum trioxide gave 435 (R = Me) via an intermolecular cyclocondensation (89MI87). Regioselective cycloaddition of propargylic alcohol and dimedone in the presence of thiolate-bridged diruthenium complex afforded the tetrahydrobenzo[fr]pyran 451 (04JOC3408). 

A range of thiazoles with various combinations of Ri, R2, and R3 substituents was synthesized using this method. The silver-catalyzed cycloaddition of propargylic alcohol with thioamide was proposed to proceed through the intermediacy of a propargylic cation or the corresponding allenyl cation and its subsequent reaction with the nucleophilic sulfiir of thioamide, followed by a 5-exo-dig attack by nitrogen. 

Thiolate-bridged dirutheniutn complexes catalyze the [3-f3] cycloaddition reaction between propargylic alcohols and cyclic 1,3-dicarbonyl compounds to afford 4,6,7,8-tetrahydrochromen-5-ones or 4//-cyclopenta[b]pyran-5-ones [193] and with 2-naphthols or phenols to afford l//-naphtho[2,l-b]pyrans and 4//-l-benzo-pyrans, respectively [194]. This cycloaddition is considered to proceed by stepwise propargylation and intramolecular cyclization (carbon and oxygen nucleophile additions) reactions, where ruthenium allenylidene and vinylidene complexes are the key intermediates (Scheme 57). Enantioselective mthenium-catalyzed [3-f3] cycloaddition of propargylic alcohols with 2-naphthols has also been described [195]. 

Reactions of propargylic alcohols with 2-naphthol gave the cycloaddition products such as ll-f-naphtho[2,l-fo]pyrans in excellent yields with complete selectivity... 

The generation of mthenium carbenoid intermediates can also arise from propargyl alcohols. In the presence of the CpRuCl(PPh3)2 complex, p-oxomthenium carbenoids were presumably formed via redox isomerization of propargyl alcohols. This process applied to enynols allowed the synthesis of [3.1.0] and [4.1.0] bicyclic frameworks by [2+2] cycloaddition of the ruthenium carbenoid species with the double bond of enynols followed by reductive elimination [127] [Eq. (60)]. 

The synthesis of 1//-1,2,3-triazoles has been usually carried out by phenylacety-lene and sodium azide. Other routes to 1//-1,2,3-triazoles include the reaction of sodium azide with nitroalkenes [74] and alkenyl bromides the reaction of ( )-P-arylvinyl bromides and sodium azide [75], which is catalyzed by Pd2(dba)3 and Xantphos the cycloaddition of propargyl cations derived from corresponding alcohols with azides [76]. 

Enyne metathesis starting either from acetylenic boronates and homoallylic alcohols [104a,c] or from propargyl alcohols and allylboronates [104b] has recently been described. The resulting boronated dienes can be converted to allenes or cycloaddition products. The cross metathesis of vinylcyclopropyl-boronates directed toward the total synthesis of natural products has very recently been investigated by Pietruszka et al. [104d]. 

We now report the synthesis of new antibacterial 3H-pyrazoles by regioselective 1,3-dipolar cycloaddition of the versatile 2-diazopropane to nonprotected disubstituted propargyl alcohols and that the unsubstituted propar-gyl alcohol allows the double addition of 2-diazopropane and gives a 3H-pyrazole with formal insertion of the dimethylcarbene into a carbon-carbon bond. We also show that the photolysis of the 3H-pyrazoles leads to new alcohols containing the cyclopropenyl unit. 

Whereas the Rh2(OAc)4-catalyzed addition of diazoalkanes to propargyl alcohols readily gives the insertion of the carbene into the 0-H bond, with only a small amoimt of cyclopropenation of the resulting propargylic ether [54] the 2-diazopropane 59 reacts at 0 °C with l,l-diphenyl-2-propyn-l-ol 62a in dichloromethane and exclusively gives, after 10 h of reaction, only the adduct 63a isolated in 75% yield and corresponding to the regioselective 1,3-dipolar cycloaddition of the 2-diazopropane to the alkyne C - C bond (Scheme 15). 

Analogously, the 1,3-dipolar cycloaddition reaction of 2-diazopropane with propargyl alcohol 62b, performed at 0 °C in dichloromethane, was completed in less then 10 h and led to a monoadduct 63b with the same regioselective addition mode of 59 to the triple bond. The HMBC spectrum showed correlations between the ethylenic proton and the carbons C3 and C5 and between the methyl protons and the carbons C3 and C4. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

Copper(l) halides can promote the cycloaddition reaction of C02 with propargylic alcohols and aliphatic primary amines also in scC02 (333 K, 8 MPa) to give... 

A tandem sequence of double [2,3]-sigmatropic rearrangement-six-electron electro-cyclization-4 + 2-cycloaddition has been shown to convert acyclic ene-bis(propargyl alcohols) such as (71), via the corresponding bis-sulfenic ethers such as (72), into anthracene (with an intermolecular final cycloaddition) or phenanthrene or related (with an intramolecular cycloaddition) skeletons. The sequence is illustrated in Scheme 12 for synthesis of a steroid skeleton, estra-l,3,5(10)-trien-17-one (73).81... 

The thiolate-bridged diruthenium complex 101 can promote a cycloaddition reaction between propargylic alcohols and 1,3-dicarbonyl compounds to provide 3-acyM//-pyrans in excellent yield (Scheme 33). The reaction proceeds via formation and alkylation of the allenylidene complex 102 to form the vinylidene intermediate 103, which upon cyclization furnishes 4//-pyrans (Scheme 33) <2004JOC3408>. 

Substituted phthalides can be prepared in a [2+2+2] cycloaddition of two molecules of methyl propiolate with propargyl alcohol. This cyclotrimerization, which is catalyzed by a cobalt(ll)-DPPE complex in the presence of catalytic amounts of zinc, affords the reaction products in acceptable to good yields (Equation 150) <2005CC4955>. 

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