Chroman-8-carboxylates

Salicylic esters prepared by [3+3] cycloadditions between l,3-bis(trimethylsilyloxy)-7-chlorohepta-1,3-dienes and free or protected 1,3-diketones undergo a Williamson cylisation to yield chroman-8-carboxylate esters (Scheme 12). Application of this methodology to... 

Chroman-2-carboxylic acid, 2-hydroxy-4-oxo-ethyl ester synthesis, 3, 852... 

Chroman-2-carboxylic acid, 6-hydroxy-2,5,7,8-tetramethyl-as antioxidant, 3, 718 oxidation, 3, 725... 

Chroman-4-carboxylic acid, 6,7-dimethoxy-3-oxo-ethyl ester... 

Chroman-6-carboxylic acid, 8-hydroxy-2-methyl-4-0X0—see Rosellinic acid, 718 Chroman-2,7-dicarboxylic acid, 2,4,4-trimethyl-formation, 3, 733... 

Chromans with defined stereochemistry are accessible by manipulation of dihydrochromeno[3,2-b]azete-2,8-diones 26 which result from the cyclisation of azetidine-2-carboxylic chlorides 25 <99T5567> and also from chroman-4-ones via an initial enantioselective reduction by BHj in the presence of Coreyls oxazaborolidine <99T7555>. 

Chlorination or bromination of isothiochroman yields the corresponding 1-halo derivatives,241,252 253 which are intermediates for numerous isothiochromans since the halogen atoms are benzylic and, therefore, very susceptible to nucleophilic substitution. Thus, 1-chloroisothio-chroman wth mercuric cyanide gives the 1-cyano derivative, which provides the 1-carboxylic acid, 1-ester, and the 1-amide.239,252 The remaining 1-H of the 1-cyano derivative is acidic and, with base,... 

Several chroman-3- and -4-ones have been catalytically reduced to the alcohol, for example, ethyl 6,7-dimethoxy-3-oxochroman-4-carboxylate (660) (58BCJ267) and 3-acetamido-2-methylchromanone (661), the latter to the chroman in two stages (73JCS(P2)227). 

An unusual oxidative breakdown of a p-tolyl group to a carboxylic acid (688) is accomplished in moderate yield without degrading the chroman system (51JCS76) and the stability of this system to oxidation (cf. chromone, Section 2.23.9.3) is further illustrated by the conversion of an ethyl to a carboxyl group in the formation of 2,4,4-trimethylchroman-2,7-dicarboxylic acid (689) (57JCS3060). 

The chroman ring system is stable to organometallic reagents, for example in the formation of the tertiary alcohol (690) in high yield (63HCA650), and to the usual interconversion of carboxylic acid, acyl chloride, carboxamide and nitrile. 

The stereochemical consequences of the cyclization of some 3-(2,5-dihydroxyphenyl)pro-pan-l-ols (247) have been investigated, with a view to optimizing the chiral economy of a tocopherol synthesis from (S)-chroman-2-carboxylic acid (81JOC2445). It was observed that acid-catalyzed dehydration occurred with retention of configuration and it was proposed (79JA6710) that the process involved the formation of a hemiketal through nucleophilic attack by the side-chain hydroxy group on the keto tautomer. 

Ring closure of a 2-methoxyphenyl derivative of propanol to a chroman has also been achieved. Treatment of the aryloxazoline (259) with sodium hydride yielded the chroman (260) (81JOC783). The intramolecular nucleophilic displacement of the o-methoxy group is promoted through oxazoline activation and proceeds through an addition-elimination sequence. The initial attack involves coordination of the metal alkoxide to both the oxazoline moiety and the methoxy group, and aromatization follows with displacement of methoxide ion (Scheme 67). Hydrolysis of the oxazoline moiety to a carboxyl group has been accomplished. 

A 2,2-disubstituted chromanone results from the condensation of o-hydroxyacetophenone with diethyl oxalate. The initially formed 1,3-diketone cyclizes spontaneously to ethyl 2-hydroxy-4-oxochroman-2-carboxylate (77LA1707). The enolate also reacts with aliphatic ketones to give 2,2-disubstituted chroman-4-ones via the diol (79TL3685). 

The intramolecular C-H insertion of a-diazocarbonyl compounds proceeds with excellent regioselectivity affording chroman-4-ones and with good enantioselectivity when Rh (II) carboxylates are used as the catalyst (95JCS(P1)1373). 

Ring opening of a bi- or tricyclic /3-lactam, which does not have a bridgehead nitrogen atom and whose relative stereochemistry is known, gives /3-amino acid derivatives where the relative stereochemistry is also known. This idea has been used extensively. For instance, methanolysis of the tricyclic /3-lactams 117 gave a series of 3-amino 4-substituted chromane-2-carboxylic esters 118 (Equation 12) whose relative stereochemistry is known <1999T5567>. 

A new type of photo-dimerization reaction for coumarin derivatives has also been described (Equation 16) <2002TL5161>. Irradiation of coumarin-3-carboxylic acid 180 in ethanol provided three different types of products the 4,4 -dimer of chroman-2-one 181, 3-(l -hydroxyethyl)-coumarin 182, and coumarin 183. The authors postulated that for the formation of 181, a ketyl radical is first formed, and the equilibrium between the 2-position and 4-position radical favors the latter. Dimerization of the 4-position radicals, followed by tautomerization and decarboxylation, provides dimer 181. 

Chroman, 4-( p-hydroxyphenyl)-2,2,4-trimethyl-X-ray studies, 3, 622 Chroman, 2-methoxy-synthesis, 3, 806 Chroman, 5-methoxy-synthesis, 3, 778 Chroman, 7-methoxy-synthesis, 3, 778 Chroman, 8-methoxy-acylation, 3, 732 Chroman, 2-methoxy-2-methyl-synthesis, 3, 780 Chroman, 2-methyl-synthesis, 3, 785 Chroman, 5-methyl-reactivity, 3, 732 Chroman, 6-nitro-synthesis, 3, 784 Chroman, 4-phenyl-synthesis, 3, 783 Chroman, thio-metabolism, 1, 241 Chroman, 5,6-thio-2-substituted metabolism, 1, 241 Chromanamines H NMR, 3, 580 Chroman-3-amines conformation, 3, 630 (S) -Chroman-2-carbaldehyde synthesis, 3, 779 Chromancarbaldehydes synthesis, 3, 782 Chroman-4-carbamic add synthesis, 3, 782 (R)-Chroman-2-carboxylic add methyl ester... 

Conventional condensation of 1,2-diaminobenzene 16 with 6-fluoro-3,4-dihydro-2H-chroman-2-carboxylic acid 17 under Phillips conditions or using Eaton s reagent (1 10 mixture of phosphorus pentoxide/methanesulfonic acid) yielded 2-(6-fluorochroman-2-yl)-lff-benzimidazole 18 (Scheme 4) [30]. However, irradiating the reaction mixture containing polyphosphoric acid as a catalyst with microwaves afforded the compoimd 18 in comparable yields in a matter of three minutes [30]. 

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