Alkenol cyclizations

Analogously, a number of 2-fluoro-4-alkenols cyclize upon treatment with mercury(II) trifluo-roacetate in tetrahydrofuran8. Generally, the trans-2,5-relationship is predominant8. 

Furthermore, the double-bond configuration strongly influences the stereochemical outcome of 5-alkenol cyclization. Thus, starting from ( )-2-methyl-9-undecen-5-ol [( >8], the 2,6-c/j-te-trahydro-2//-pyran-2-acetate 9A is the major component of the reaction mixture, whereas starting from (Z)-8 the 2,6-trfliw-derivative 9C is exclusively obtained82. 

Scheme 11 Alkenol cyclizations catalyzed by cerium and bismuth Lewis acids...

Lanthanoids As mentioned in several cases above, some lanthanoid triflates displayed more or less catalytic activity for alkenol cyclizations. In one optimized case, several alkenol cyclizations were performed with Ln(OTf)3, Sm(OTf)3, and Yb(OTf)3 as catalysts (1 mol%) at 120°C in an ionic liquid as solvent (W-ethyl-W-methyl-imidazolium triflate) [73]. Addition of 2,6-di-ferf-butylpyridine blocked the activity of Yb(OTf)3 nevertheless, the authors argue that triflic acid, even though it catalyzed the reaction in a blind test, could not have been the hidden active catalyst, because triflic acid was not found by NMR spectroscopy in a vacuum transfer of volatiles from the reaction solution. 

Related V complexes show activity toward the oxidative decomposition of pinacol with C—C bond cleavage and aerobic oxidation of 4-methoxybenzylalcohol and other lignin model compounds." Other oxidovanadium(V) complexes with c 5-2,6-bis-(methanolate)-piperidine ligands of the type depicted on Scheme 3 were appHed as catalysts to convert prochiral alkenols into 2-(tetrahydrofiiran-2-yl)-2-propanols, 2-(tetrahydropyran-2-yl)-2-propanols, oxepan-3-ols and epoxides, upon oxidative alkenol cyclization with TBHP as oxidant (Scheme 3)." These catalysts are rather stable and possess improved chemoselectivity, e.g., epoxidation of geraniol occurs enantioselectively. It was ruled out the vanadium(V) ieri-butyl peroxy complex formation is a key step to activate peroxides. 

Donges M, Amberg M, Stapf G, Kelm H, BergstraBer U, Hartung J. cis-2,6-Bis-(methanolate)-piperidine oxovanadium(V) complexes as catalysts for oxidative alkenol cyclization by tert-butyl hydroperoxide. Inorg Chim Acta. 2014 420 120-134. 

The structure of glabrescol was subsequently revised, and the new structure was synthesized enantioselectively through sequential hydroxy-directed anti-oxidative cyclization of acyclic y-alkenols with VO(acac)2/TBHP to construct the adjacent THF rings via epoxides under acid conditions [35b],... 

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... 

In Case 1 both the ring closure steps (with rate constants ks and kR) are faster than dissociation of the 7r-complexes to reform the alkenol and N-X+ species. Here the [S]/R] product ratio is determined only by the difference in the activation energy leading to the 7is- and rcR-complexes because immediately after these are formed the cyclization occurs. Thus, the chirality is set by the approach of the alkene to the halonium ion. 

Following the results obtained in the intermolecular carbonylation of alkenes in the presence of alcohols, it seemed conceivable that an alkene-bearing alcohol functionality would react in an intramolecular way giving a cyclic ester as the main product. Thus, the carbonylation (also referred to as cyclocarbony-lation as a cyclization occurs simultaneously) of alkenols (or hydroxyalkenes) was investigated for the selective preparation of lactones. 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

The levels of 1,5-asymmetric induction in the palladium-catalyzed alkoxy-carbonylations of alkenols to form 2,6-disubstituted tetrahydropyrans have been shown to be quite reasonable (Table 10 and equation 50).144 Recent studies have shown that cyclization with palladium(II) acetate in DMSO in the absence of CO results in controlled -hydride elimination to form vinyl-substituted tetrahydropyrans with high levels of 1,4- and 1,5-asymmetric induction (equation 51).144b... 

The mercury(ll)-promoted cyclization of alkenols to afford chromans continues to attract attention and is seen during the synthesis of a cannabinoid analogue 397 (Equation 165) <1998JME3596>. Intramolecular cyclization of the methyl ester 398 to form the 2,2-disubstituted chroman 399 can be achieved by a tandem demethylation/cyclization sequence using AlCb/EtSH via the intermediate 400 (Scheme 94) <2000MOL880>. Cyclizations of this type can also be effected by SnCLj- <1997S23>. 

When phenylseleno derivatives are employed to prepare tetrahydrofurans from 4-alkenols, moderate stereoselectivity is generally observed. Cyclization of syn-(Z,Z)-7-benzyloxy-3,9-di-en-6-ol (22) with phenylselenyl chloride in dichloromethane at — 78 °C affords the corresponding 2,5-disubstituted tetrahydrofuran in 89% yield and 75 25 (trans/cis) diastereomeric ratio12. 

Trisubstituted tetrahydrofurans can also be prepared with total stereoselection by cyclization of 3-alkenols performed with Ar-(phenylseleno)phthalimide (N-PSP) in dichloromethane135. 

The stereoselection of the reaction relies on the double-bond configuration. In fact, either anti-or. un-(Z )-2-methyl-3-alkenols afford predominantly a single product, whereas the cyclization of rw/7-(ZD-2-methyl-3-alkenol 2 proceeds with lower stereoselection. 

Synthesis of Tetrahydrofurans by Cyclization of 4-Alkenols Mediated by Palladium(II) or Palladiuin(O)... 

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