Phenol, 2-Allyl

You have already seen that a carbon-heteroatom bond is easy to make, since we used such bonds as natural places for disconnections (frames 234 ft). It is good strategy therefore to make a carbon-heteroatom bond and then to transform it into a carbon-earbon bond. The Claisen rearrangement is one way to do this an ortho allyl phenol (B) made from an allyl ether (A) ... 

Claisen rearrangement (Section 24 13) Thermal conversion of an allyl phenyl ether to an o allyl phenol The rearrange ment proceeds via a cyclohexadienone intermediate... 

The discovery of the utility of the bis-chromone carboxylic acid derivative cromolyn sodium in the treatment of asthma and related allergies has led to an intensive, and thus far not very fruitful, effort to discover analogues which would show oral activity in contrast to the lead which must be administered by inhalation. Preparation of a typical analogue, proxicromil (63), starts with the O-allylated phenol 57. Claisen rearrangement leads to the corresponding C-allylated product 58. 

The rearrangement of an O-allyl ether (LXXV) to form the isomeric ortho allyl phenol (LXXVI)... 

Sheldon and co-workers (Elings et al, 1995) have used H-Mordenite to rearrange allyl phenyl ether to 2-allyl phenol and subsequent cyclysation to 2-methyl dihydrobenzofuran. 

Some allyl phenyl ethers with an alkyl substituent on the end carbon of the allyl group rearrange to give the normal ortho-Claisen product together with another isomeric O-allyl phenol. The latter, formed by the rearrangement of the normal product, has been established. This is called abnormal Claisen rearrangement, is illustrated by the following example. 

Allyl ethers when heated yield allyl phenols (Claisen),... 

A variety of unsaturated alcohols with a cyclic structure and allyl phenols lead to bicycUc telluroethers. 

Phenolic derivatives were prepared and then converted into thioether analogs using ethanedithol followed by oxidation of this intermediate to the disulfide. Phenolic resins were prepared by electrophilic substitution of allyl phenol derivatives with formaldehyde and then flee radically copolymerizing with ethanedithol. Epoxidation was performed using epichlarohydrine. 

The ring closure of o-allyl phenols has been extended to the synthesis of several other types of fused furans. 

Synthesis of 2-(1-Hydboxyalkyl)-2,3-dihydrobenzofttrans fbom o-Allyl Phenols (168) AND... 

Allyl phenyl ethers rearrange cleanly at high temperatures, producing 0-allyl phenols or -allylphenols if both ortho positions are blocked. This reaction is called the Claisen rearrangement (10). 

Recall that the Claisen rearrangement converts an aryl allyl ether to an ortho-substituted allyl phenol. The presence of an allyl substituent in the product ortho to an aryl ether thus suggests the following retrosynthesis ... 

As reported in the literature synthesis, the starting phenol may be converted to the corresponding allyl ether by reaction with allyl bromide in the presence of base. This step was accomplished in 80% yield. Heating the allyl ether yields the o-allyl phenol. 

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 structure of XXVI was deduced from the fact that it was different from the 2-cinnamylphenol obtained by direct C-cinnamylation of phenol.16 Later investigators showed that XXVI is the sole product ozonization yielded formaldehyde but not benzaldehyde. 7-Methyl-allyl phenyl ether also rearranges with inversion, yielding 2-(a-methyl-allyl)-phenol 36 the structure of the rearrangement product has been definitely established87 38 by a combination of degradative and synthetic procedures. 

The same procedure, with a refluxing time of one hour, gives a 73% yield of 2,3-dimethyldihydrobenzofuran when applied to 2-(a-methyl-allyl)-phenol.86... 

The facile electrocyclic ring closure of ortho-quinone methides provides a convenient strategy for the synthesis of 277-chromenes. Oxidation of ortho-allylic phenols using DDQ or potassium dichromate is a popular method for the formation of 277-chromenes, via ortho-quinone methide intermediates, and is discussed in detail in the preceding volumes (Scheme 6) <1984CHEC, 1996CHEC-II>. 

The palladium(n) catalyzed cyclization of ortho-allylic phenols can lead to a mixture of benzopyran and benzofuran products. The palladium(ll) catalyzed cyclization of ortho-allylic phenols, which bear a variety of substituents on both the aryl ring and the allyl group, in the presence of KHCO3 in DMSO-water (9 1) affords 2//-chromenes exclusively (Equation 15) <1998SL522>. Lower yields of 2//-chromenes are obtained when electron-withdrawing groups are... 

Iodine-mediated removal of both prenyl protecting groups from aryl ether 506 leads to the unexpected formation of 3-(3-iodo-2,2-dimethylchroman-6-yl)propan-l-ol. The reaction proceeds via formation of the ortho-allylic phenol intermediate 507 by electrophilic removal of a prenyl species, followed by an iodine promoted electrophilic cycliza-tion (Scheme 111) <2001SL1989, 2002T5689>. 

The classical Claisen rearrangement is the first and slow step of the isomerization of allyl aryl ethers to orf/to-allylated phenols (Figure 11.41). A cyclohexadienone A is formed in the actual rearrangement step, which is a [3,3]-sigmatropic rearrangement (see Section 11.1 for the nomenclature of sigmatropic rearrangements). Three valence electron pairs are shifted simultaneously in this step. Cyclohexadienone A, a nonaromatic compound, cannot be isolated and tautomerizes immediately to the aromatic and consequently more stable phenol B. 

The original sigmatropic rearrange-J ment occurred when an aryl allyl ether was heated without solvent and ail ortho-allyl phenol resulted. 

---