Cyclizations ethers

The total synthesis of ( )-ancistrofuran has relied on the ene reaction of N-phenyltriazolinedione (PTAD, 564) with the alkylidene lactone (563) (81JOC1198,80JOC4287), Upon completion of this room temperature reaction an attempt was made to acetylate the free NH group in (565) (2 1 mixture of diastereoisomers). The cyclized ethers (566) and (567) were, however, obtained instead. The triazolinedione thus functions as a very good... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

The cyclized products 393 can be prepared by the intramolecular coupling of diphenyl ether or diphenylamine(333,334]. The reaction has been applied to the synthesis of an alkaloid 394[335]. The intramolecular coupling of benzoyl-A-methylindole affords 5-methyl-5,10-dihydroindenol[l,2-b]indol-10-one (395) in 60% yield in AcOH[336]. Staurosporine aglycone (396) was prepared by the intramolecular coupling of an indole ring[337]. 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Allyl aryl ethers are used for allylation under basic conditionsfh], but they can be cleaved under neutral conditions. Formation of the five-membered ring compound 284 based on the cyclization of 283 has been applied to the syntheses of methyl jasmonate (285)[15], and sarkomycin[169]. The trisannulation reagent 286 for steroid synthesis undergoes Pd-catalyzed cyclization and aldol condensation to afford CD rings 287 of steroids with a functionalized 18-methyl group 170]. The 3-vinylcyclopentanonecarboxylate 289, formed from 288, is useful for the synthesis of 18-hydroxyestrone (290)[I7I]. 

The cyclohexadiene derivative 130 was obtained by the co-cyclization of DMAD with strained alkenes such as norbornene catalyzed by 75[63], However, the linear 2 1 adduct 131 of an alkene and DMAD was obtained selectively using bis(maleic anhydride)(norbornene)palladium (124)[64] as a cat-alyst[65], A similar reaction of allyl alcohol with DMAD is catalyzed by the catalyst 123 to give the linear adducts 132 and 133[66], Reaction of a vinyl ether with DMAD gives the cyclopentene derivatives 134 and 135 as 2 I adducts, and a cyclooctadiene derivative, although the selectivity is not high[67]. 

Pd(II)-catalyzed cyclization of the siloxyhexatriene 34 offers a cyclohexe-none annulation method. The Pd enolate 35, formed by transraetallation of the silyl enol ether with Pd(II), is an intermediate which undergoes intramolecular eWo-alkene insertion. Then Pd(II) is regenerated to give 36, and finally cyclohexenone is formed[38]. 

Owing to the instability of a-halogenoaldehydes it is occasionally preferable to use more stable derivatives, such as enol acetate prepared according to Bedoukian s method (204) and a-bromoacetals (4, 8, 10, 16, 22, 67, 101, 426). An advantage is said to be in the yield however, this appears to be slight. The derivatives react in the same sense as the aldehydes themselves, that is, the acetal group as the more polarized reacts first and enters the C-4 position. It is likely that the condensation and cyclization occur by direct displacement of alkoxide ions. Ethyl-a,/3-dihalogeno ethers (159, 164, 177, 248) have also been used in place of the free aldehydes in condensation with thioamides. 

The first step of the reaction involves the formation of the S-C bond with the elimination of a molecule of ammonium salt. The fact that it has been possible to isolate the acyclic intermediate (176), R = Me or Ph, would confirm this hypothesis, particularly when the reaction is carried out for a short time in the cold in ethereal solution (27, 82). These intermediates (176) can be cyclized quantitatively on standing or on being treated by hydrochloric acid. However, no evidence has been advanced concerning their structures. 

The cyclization of a-mercaptoketones with ammonium thiocyanate leads to the corresponding 2-mercaptothiazoles (144). For example, 2-mercapto-3-pentanone in ethereal solution with sulfuric acid gives 4-ethyl-5-methyl-2-mercaptothiazole (10), Ri = SH, R2 = Et, R3 = Me, when allowed to stand for 3 hr without heating with ammonium thiocyanate. 

Haloalkylthiazoles are generally prepared by cyclization or from the corresponding hydroxyalkythiazole. They in turn can lead to numerous functional derivatives, such as aminoalkylthiazoles (33-42.50. 854), ethers... 

Base promoted cyclization of vicinal halohydrms (Section 16 10) This reaction is an intramolecu lar version of the Williamson ether synthesis The alcohol function of a vicinal halohydrin is con verted to its conjugate base which then displa ces halide from the adjacent carbon to give an epoxide... 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

With an amine reactant, it has been shown that roughly one-third of the current passed makes Hquid product, one-third gas, and one-third goes to HF-soluble polyfluorinated products (24). The ether perfluoro(2-butyltetrahydrofuran) [335-36-4] is made from a cyclization process during the ECF of perfluorooctanoyl chloride other cycHc ethers have been prepared from certain ester reactants by a similar cyclization (25). Perfluoroaminoethers have been prepared by ECF (26). 

Diallyl Isophthalate. DAIP polymerizes faster than DAP, undergoes less cyclization, and yields cured polymers of better heat resistance, eg, up to ca 200°C. Prepolymer molding materials such as Dapon M of EMC, are not sticky. Maleic anhydride accelerates polymerization, whereas vinyl isobutyl ether retards it and delays gelation in castings. Copolymers with maleic anhydride are exceptionally hard and tough and may scratch homopolymer surfaces. 

The need for pyrazoles substituted with the trifluoroacetyl group led to the reaction of ethoxyvinyl ether with trifluoroacetic anhydride, yielding 4-ethoxy-l,l,l-trifluoro-3-buten-2-one (38) this further reacted with aldehyde / fZ-butyUiydrazones, and after cyclization at room temperature under mildly acidic conditions the pyrazoles were obtained in satisfactory yields (eq. 7). Further treatment with H2SO4 removed the tert-huty group, thus providing an opportunity for further derivatization at N. ... 

In some instances, ring contraction is accompanied by cyclization to indole derivatives. For example, l-aryl-6-oxo-l,4,5,6-tetrahydropyridazines with a carboxyl or methyl group at position 3 give indoles when treated with an ethanolic solution saturated with hydrogen chloride or in the presence of BF3 etherate. 

Large ring heterocyclic radicals are not particularly well known as a class. Their behavior often resembles that of their alicyclic counterparts, except for transannular reactions, such as the intramolecular cyclization of 1-azacyclononan-l-yl (Scheme 1) (72CJCH67). As is the case with alicyclic ethers, oxepane in the reaction with r-butoxy radical suffers abstraction of a hydrogen atom from the 2-position in the first reaction step (Scheme 2) (76TL439). 

Friedel-Crafts cyclization benzo[i]thiophenes from, 4, 873 Ethanol, 2-(4-imidazolyl)-synthesis, 5, 484 Ethanol, (S)-l-phenyl-synthesis, 1, 434 Ethanol, 2-phenyl-isochroman synthesis from, 3, 788 Ether, allyl pyridyl... 

B. Cyclization. The above oil is poured dropwise into a well-stirred mixture of 110 ml. of 90% phosphoric acid (sp. gr. 1.75) and 23.4 ml. of sulfuric acid (sp. gr. 1.83) which is kept at —10°. The temperature is allowed to rise to 0-10°, and the stirring is continued for 2 hours. The viscous reaction mixture is poured into 500 ml. of ice and w ater, and the acid is partially neutralized with 300 ml. of 40% sodium hydroxide solution with efficient cooling. The viscous cream-colored oil is extracted with three 150-ml. portions of ether the ether extract is washed well with water and sodium bicarbonate solution to remove the last traces of acid and then dried over anhydrous sodium sulfate. The... 

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