Propargyl ether, cyclization

Two groups independently demonstrated that the strategy for the preparation of 55 could be used for the synthesis of 2-substituted-3-allenylbenzo[b]furans 59 (Scheme 3.31). The synthesis of 59 was achieved by intermolecular cyclization between alkynylphenols 56 and propargyl carbonates 57 [67] or by intramolecular rearrangement of (2-alkynylphenyl)propargyl ethers 58 [67, 68]. 

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

Sames et al. studied the cyclization of phenyl/propargyl ethers catalyzed by different metal salts since this Friedel-Crafts alkenylation had previously been reported to be catalyzed by metals such as Pd, Zr In and Sc [122-124] or even zeolites by hereogeneous catalysis [125]. In this preliminary research, the maximum yield of the desired product achieved by gold was only 6%, the best results being obtained with PtCl2 as catalyst [126]. 

N. Moufid and Y. Chapleur, Radical cyclization of allyl propargyl ethers and acetals application to the stereocontrolled acylation of carbohydrates, Tetrahedron Lett. 32 1799 (1991). 

A particularly useful chromene synthesis involves the thermal rearrangement in an inert solvent of aryl propargyl ethers (33) (62CPB926,63CPB1042) which are conveniently prepared from a phenol and a chloroalkyne. An indication of the ease of cyclization is apparent from the presence of chromene in the ethers prepared in this manner. 

Electron-withdrawing m-substituents will decrease the electron density at the aromatic terminus of the [3,3]-rearrangement, thereby retarding the reaction. This allows polymerization of the terminal alkyne to compete successfully with the cyclization. However, the presence of a m -substituent has a much more significant effect the cyclization of m-substituted aryl propargyl ethers can lead to two isomeric products (46a and b). 

Table 2 Isomer Distribution in the Cyclization of m-Substituted Phenyl Propargyl Ethers...

The use of Lewis acids in controlling the stereoselective outcome of radical cyclization reactions has been explored, in particular the effect of aluminium-based Lewis acids using low temperature Et3B/Bu3SnH-initiated procedures.171,172 For example, cyclization of propargyl ether (78) or allyl ether (79) in the presence of Lewis acid (80) can completely reverse the normal selectivity (Scheme 34).171 The effect of aluminium Lewis acids on the diastereoselectivity of 6-exo cyclization of unsaturated chiral menthol esters has been studied.172 Cyclization at low temperature in the presence of the Lewis acid MAD modified the de of the reaction from 31 to 98%. 

Iodobenzyl propargyl ether 57 cyclizes with 7t-allylpalladium (Scheme 18) to form after trapping by a secondary amine tetrahydro-2-benzoxepines 58 in 70% yield. The piperidino derivative 58 (R2 = (CH2)5) undergoes Diels-Alder reaction with 4-phenyl-l,2,4-triazole-3,5-dione as dienophile to give a spiro derivative 59 in 44% yield <1996TL6565>. 

Reaction of the unsaturated bromoethyl glycoside 216 in the foregoing manner gives the bicyclic product 217,218 and similar treatment of the propargyl ether 219 with a tributyltin radical results in carbon-radical generation and cyclization to afford the tin-containing adduct 220 in 90% yield. On oxidation with osmium tetraoxide and periodate ion, the Sn-C bond is cleaved, and the corresponding ketone 221 is produced in excellent yield.219... 

Cyclization of allyl propargyl ethers.2 This Pd complex is far superior in re-... 

The silver-catalyzed, propargyl Claisen rearrangement has also been combined with cyclization reactions. Propargyl ethers derived from [3-ketoesters were rearranged by silver hexafluoroantimonate and the resulting allenic [3-ketoesters cyclized on treatment with base, leading to the formation of 2/7-pyrans in moderate to excellent yields (Scheme 3.48).75 The cyclization process was described as a base-catalyzed... 

Early examples of catalytic radical cyclizations were provided by Okabe and coworkers, who subjected 2-bromoethyl propargyl ethers or bromoacetaldehyde propargyl acetals 257 to complex 255 as a catalyst and sodium borohydride as the stoichiometric reducing agent (Fig. 63, Table 5, entry 1) [307, 308]. 

Last and Hoffmann described 5-exo radical annulation reactions of cyclic p-bromo propargyl ethers or acetals 259 (X=CH2) and their benzo analogs catalyzed by 5 mol% 255 as an approach towards the total synthesis of aflatoxins and analogs (entry 3) [311]. The cyclizations gave the products 260 in 35-95% yield. 

Cobaloxime 255 was also applied as a catalyst (6 mol%) in a cyclization of 2-bromo-l,2-diphenylethyl propargyl ether 257 or bromoindanyl propargyl ether 259 to afford 3-methylenetetrahydrofurans of type 258 or 260 in 50% and 57% yields, respectively (entry 4) [312, 313],... 

Fig. 27 Reductive nickel(I)-catalyzed radical cyclizations of bromo propargyl ethers 113...

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