Phenols chromanes from

Chromans.—The use of isoprene in the synthesis of chromans from phenols is a well known reaction but one which is fraught with difficulties since regiochemical control is poor, In a re-examination of the problem Sartori et al have found... 

Several chromans have been synthesized using the Parham cycloalkylation technique (76JOC1184). l-Bromo-3-(2-bromophenoxy)propane, prepared from phenol and 1,3-dibromopropane, is treated with n-butyllithium at — 100 °C. Halogen-lithium exchange yields the aryllithium (278) which cyclizes either at — 100°C or in some instances only at an acceptable rate at higher temperatures. This method offers the advantage of regio-specificity since cyclization is controlled by the location of the o-bromine atom (Scheme 72). 

The substantial drawback of BPA synthesis from phenol and acetone is the formation of more than 30 various b3q>roducts in the side reactions occurring during the process (Figure 7.9) [53,54]. These are mainly the isomers of BPA, i.e., the o,p-isomers of BPA, the Dianin s compound, chromans, trisphenols and polyphenols as shown in Figure 7.10. 

Stokes, S. M. J. Ding, F. Smith, R L. Keane, J. M. Kopach, M. E. Jervis, R. Sabat, M. Harman, W. D. Formation of o-quinone methides from T 2-coordinated phenols and their controlled release from a transition metal to generate chromans. Organometallics 2003,22, 4170-4171. 

For the enantioselective synthesis of chiral chromanes such as 2-213, a chiral Lewis acid complex, formed in situ from Mg(OTf)2 and 2-212, is assumed to catalyze the domino transformation of the phenols 2-210 and the p,y-unsalurated a-ke-toesters 2-211 (Scheme 2.50). 2-213 was obtained in excellent diastereoselectivity, but only in mediocre enantioselectivity. 

Chromene acetals 39 are accessible from 2-vinyl-substituted phenols via the allylic acetals 38 through oxypalladation of benzyloxypropa- 1,2-diene and a subsequent Ru-catalysed RCM. 2-Substituted chromenes can be derived from the acetals 39 by conversion into the 1-benzopyrylium salts which are then trapped by nucleophiles (Scheme 26) <00TL5979>. In a like manner, 2-aIkoxychromans have been converted into various 2-substituted chromans by sequential treatment with SnCl4 and a silyl enol ether <00TL7203>. 

When, furthermore, phenols (368) are coupled with 1 in the presence of a Pd° catalyst, the phenoxy-methyl-1,3-dienes 369 are produced [158]. As aryl allyl ethers, these can be made to undergo a Claisen rearrangement (205 °C, DMF) and the ensuing 2-(l,3-dienylmethyl)phenols 370 finally cydize in the presence of a trace of acid to a mixture of exo-methylene chromans 371 (major product) and dihydrobenzofur-ans 372 - a remarkable generation of functional and structural complexity from simple starting materials with 100% atom economy and underlining impressively the synthetic versatility of modern allene chemistry ... 

It is pertinent at this point to refer briefly to the sources of quinone methides, though these have been reviewed (B-74M122400). The general approach used in chroman syntheses involves the thermal elimination of HX from an -substituted phenol. Commonly the eliminated molecules are water, methanol or dimethylamine (287 X = OH, OMe, NMe2, respectively). However, these methods are not entirely suitable because the eliminated molecules may promote side reactions. In the case of 1,2-naphthoquinone 1-methide, the thermal dissociation of the spirodimer (288) is a better source than the other methods. Its formation represents another example of dimerization by a [4+2]-cycloaddition, since it is prepared by heating l-dimethylaminomethyl-2-naphthol in dodecane or xylene with careful exclusion of moisture (73JCS(P1)120,81CJC2223). 

Isoflavones result from the arylation of 3-(allyloxycarbonyl) chroman-4-ones with aryllead (IV) triacetates. Of particular interest is the introduction of a 2-hydroxy function through incorporation of a protected phenolic unit into the aryllead reagent (95JCS(P1)1679). 

The reaction of salicylaldehydes with a,P-unsaturated aldehydes in aqueous dioxane and under sonification affords a mixture of 2//-[l]benzopyran-3-carboxaldehydes and a tricyclic hemiacetal. The former is considered to arise from the 1,4-addition of a phenolate ion and the latter by a vinylogons aldol reaction. The choice of base controls the relative amounts of the two products, with Na2C03 favouring the chromene and NEts the chroman. <05ASC555>. 

Chromans. - 2,4-Diethoxychromans (78) (mainly cis) represent a new type of chroman and have been prepared in high yield from a phenol (but not a deactivated phenol) and malonaldehyde bis(diethyl acetal) in the presence of SnCU they are converted into the benzopyrylium salts (79), in excellent yield, by treatment with perchloric acid. A Wittig-Horner reaction of the chiral phosphoryl ( S)-sulphoxide (81) and the ketone (80) gave the chiral sulphoxide (82), which was cyclized by aqueous alkali to a mixture which contained 22% diastereoisomeric excess of (25 )-chroman (i )-sulphoxide. This was converted, in three steps, into the aldehyde (83), which is a useful synthon for a-tocopherol. ... 

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