2-Allylphenol, cyclization

Heterocyclization. Allylmalonic acids and o-allylphenols cyclize without incorporating iodine, giving y-butyrolactones and dihydrobenzofuranes, respectively, when they are treated with in dichloromethane at room temperature. 

Other Heteroatom Nucleophiles. Alcohols and carboxylic acids also add to metal-activated alkenes, and processes for the industrial conversion of ethylene to vinyl acetate and acetals are well established. However, these processes have not been extensively used with more cort5)lex alkenes. In contrast, a number of intramolecular versions of the processes have been developed, a few examples of which are given here. Allylphenols cyclize readily in the presence of palladium(II) to form benzofurans (eq 4). Catalytic amounts of palladium acetate can be used if the reaction is carried out under 1 atm of molecular oxygen with copper diacetate as cooxidant, or in the presence of tert-butyl hydroperoxide. If instead of palladium acetate a chiral jr-allylpalladium acetate complex is used, the cyclization proceeds to yield 2-vinyl-2,3-dihydrobenzofuran with up to 26% ee. ... 

The oxazoloquinolinequinone derivative 610 was prepared from the allylphenol 605 which was transformed to the alcohol 606 and then to the aldehyde 607. Subsequent debenzylation gave 608 that was oxidized with Ce(NH4)2(N02)6 to the quinone 609 that upon cyclization with ethanolamine gave the oxazoloquinolinequinone 610 which showed... 

The regiospecificity of intramolecular palladium-induced cyclization of o-allylphenols is determined by the precise nature of the catalyst. A mixture... 

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

Phenolic oxygen participates in facile oxypalladation. The intramolecular reaction of 2-hydroxychalcone (105) produces the flavone 106(127]. The ben-zofuran 107 is formed from 2-allylphenol by exo cyclization with Pd(OAc)2, but benzopyran 108 is obtained by endo cyclization with PdCl2[128]. Normal cyclization takes place to form the furan 109 from 2-(l-phenylethenyl)phe-nol[129]. Benzofuran formation by this method has been utilized in the synthesis of aklavinione (110)[130]. 

An interesting variant on this theme involves the cyclization of substituted 2-allylphenols by A-iodosuccinimide. The 3-iodochromans, which presumably arise via a cyclic iodonium species, are readily dehydrohalogenated by base. The overall yields are generally impressive, although ring iodination can compete (79TL2545). 

Palladium-catalyzed cyclization of o-allylphenols to benzofurans has been extensively studied.11 As is usual, early systems were catalytically inefficient but continued studies led to substantial improvement. A wide range of catalyst systems work for this process. One of the most efficient, from a standpoint of catalyst turnover and chemical yield, was based on chiral TT-allylpalladium catalysts (equation 6), although the optical yields were low. y-Pyrones can also be efficiently synthesized by palladium(II)-cata-lyzed addition of phenolic OH groups to conjugated enones (equation 7).12... 

A phenolic oxygen participates in facile oxypalladation. 2-Allylphenol (55) undergoes clean cyclization to 2H-l-benzopyran (56) in DMSO under air with a catalytic amount of Pd(OAc)2 without a reoxidant. 2-Methylbenzofuran (57) is obtained when PdCl2 is used [50]. But different chemoselectivity with the Pd(II) salts was also reported [51]. Catalytic asymmetric cyclization of the tetrasubstituted 2-allylic phenol 58 using the binaphthyl-type chiral ligand 60, called (.S, .S )-ip-borax, afforded the furan 59 with 96% ee. Use of Pd(CF3 002)2 as a catalyst is essential in the presence of benzoquinone [52]. Formation of the benzofuran 62 from 61 has been utilized in the synthesis of aklavinione [53]. The intramolecular reaction of 2-hydroxychalcone (63) produces the flavone 64 [54]. 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

Enantioselective organocatalytic conjugate addition of benzo[A] furan-2-boronic acid to ap-unsaturated aldehydes was utilized to synthesize 2-substituted benzo[Z>]furan with a chiral side chain as illustrated below <07JA15438>. Asymmetric syntheses of 2,2-disubstituted dihydrobcnzo b furans were also achieved by a palladium(II)-catalyzed cyclization of 2-allylphenols in the presence of chiral bisoxazolines <07TL4083 07TL4179>. 

A convenient method for the synthesis of benzofurans proceeds via Pd(ll)-catalyzed oxidative cyclization of o-allylphenols (Equation 112) <1998JOM(560)163>. Dimethylformamide (DMF) accelerates the reaction to completion within minutes and the addition of LiCl allows the reaction be run at room temperature. 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

Benzohydrofuranes. 2-Allylphenols are cyclized oxidatively by Pd(OAc)2 (1 equiv.) to isomeric benzofuranes. In the presence of oxygen, the Pd(II) salt can be used in catalytic amounts. An example is formulated in equation (I). ... 

If this cyclization is carried out in the presence of catalytic amounts of ( —)-/3-pinene, optically active products can be formed. Thus if the cyclization of the allylphenol 1 is conducted in the presence of Pd(OAc)2 (1 mmole), Cu(0Ac)2 H20 (lOmmole), and (-)-/3-pinene (1 mmole), an excess of (S)-2,3-dihydro-2-vinyl-benzofurane (2) is formed in 12% optical yield. Surprisingly, if /3 -pinene is present in larger amounts (2 mmoles), the cyclization does not proceed. ... 

The a-methyl derivative is produced from the acetate of o-allylphenol, HOC4H6CHjCH= CHj, by the addition of hydrogen bromide in the absence of peroxides followed by dehydrohalogenation of the free phenol with potassium hydroxide. In the presence of air or peroxides the mode of addition of hydrogen bromide is reversed and cyclization gives benzo-pyran. /3-Keto derivatives ate prepared by a similar ring closure. ... 

Heterocycles. The intramolecular cyclization of o-allylphenols to form 2//-l-benzopyrans and coupling of iodoalkenylamines and (o-iodoaryl)alkylamines with allenes to give azacyclic productsare useful preparative methods. 

Heterocycliz/oHon. Indoles are obtained when anilines and trialkanolamines are treated with RuClj, PhjP, and SnCl2-2H20 in dioxane," and dihydrobenzofurans from 2-allylphenols with RuClj hydrate, AgOTf, Cu(OTf)j, and PhjP. It appears that 2-(3-butenyl)phenol also undergoes cyclization to give benzopyran derivatives. 

In the same way, Brdnsted acid catalysts such as trifluoroacetic acid substantially accelerate the Claisen rearrangement of allylphenyl ether. However, the initially formed allylphenols generally react further under the acidic reaction conditions. For instance, crotyl p-tolyl ether (219) in trifluoroacetic acid affords benzofuran 220 as the main reaction product derived from cyclization of the Claisen rearrangement product 221 (equation 151) . ... 

The earlier work on the photochemical cyclizations of o-allylphenol (93a) were commented upon in the original article in this series. Some further studies have examined the influence of aryl substituents on the reaction and the ionic nature of the process. The photochemical cyclization of the corresponding phenoxides has also been examined . Others have examined the trani.c/i-isomerism of 93b and its subsequent cyclization... 

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