2,2-Dimethyl-3-chromanone

Bromination, chlorination, nitration and Friedel-Crafts acylation of chroman give the 6-substituted derivatives in good yields by standard methods. When 6,8-dimethyl-chromanone (677) is warmed with formaldehyde in sulfuric acid, hydroxymethylation at C-5 occurs (78BCJ1874). 

The (—)-quinine-catalyzed IMA of 40 gave cw-(- -)-methoxy chromanone cou-marin (cA-41) in 67% yield with 98% ee and its trans-41 in 21% yield with lower eantioselectivity (39% ee). The Mgl2-assisted isomerization of cis-(+)-41 accompanied by demethylation followed by the reaction of the formed diastereomeric mixture of chromanone 42 (without separation) with senecioyl aldehyde in the presence of phenyl boronic acid under the same condition to construct the 2,2-dimethyl chromanone ring reported in the synthesis of (+)-inophyllum B (3). The yield of trans-(+)-43 in 61% with 91% ee and its cw-isomer (+)-43 corresponded to the (+)-calanolide D as a minor product in 23% yield with 84% ee. At last, the synthesis of (+)-calanolide A (1) was accomplished by hydride reduction of (+)-43 with... 

Chromanone, 3-acetamido-2-methyl-reduction, 3, 729 Chromanone, 3-amino-synthesis, 3, 734 Chromanone, 3-arylidene-thermoisomerization, 3, 722 Chromanone, 3-benzylidene-thermolysis, 3, 728 Chromanone, 3-bromo-2-hydroxy-benzofuran from, 3, 729 Chromanone, 6,8-dimethyl-hydroxymethylation, 3, 731 Chromanone, 2,3-epoxy-as synthon, 3, 735... 

Chromanone, 7-methoxy-2,2-dimethyl-reactions with alkali, 3, 728 Chromanone, 3-methyl-reduction, 3, 730... 

An analogous ring cleavage has been reported in 6,6-dimethyl-dibenzo[M]pyran.20 A more complex sequence of reactions has been observed for 4-carbomethoxy-3-chromanone (23) and the proposed pathway is outlined in Scheme 1 21 1,5-Hydrogen migration occurs readily in the... 

An excellent method for the preparation of gem-difluoro compounds from aldehydes and ketones consists of conversion of the carbonyl compound to the corresponding 1,3-dithiolane followed by treatment with two equivalents of l,3-dibromo-5,5-dimethylhydantoin (DBH) and pyridinium poly(hydrogen fluoride) (HF-pyridine) in methylene chloride. Attempted extension of this procedure to 7-methoxy-2,2-dimethyl-4-chromanone, however, gave only the dihydro- 1,4-dithiin derivative 1 in 78% yield. This transformation, which proceeded in excellent yield with a variety of 4-chromanones, was found to require only the DBH (i.e. fluoride ion played no role). 

Figure 4. Synthesis of precocene. Reaction of an appropriate phenol with dimethyl acrylic acid and polypnosphoric acid (PPA) on the steam bath gives the chromanone in quantitative yield. Reduction with lithium aluminum hydride (LAH) and brief treatment with 4N hydrochloriic acid gives the chromene.

Ishikawa et al. reported that ( )-quinine-catalyzed asymmetric intramolecular oxo-Michael addition (IMA) of 7-hydroxy-8-tigloylcoumarin gave cis-2,3-dimethyl-4-chromanone systems with high enantioselectivity and moderate diaster-eoselectivity, especially when chlorobenzene was used as a solvent. " Therefore, total synthesis of (+)-calanolide A (1) was achieved by application of the (—)-quinine-catalyzed asymmetric IMA. However, the synthetic route starting from 1,3,5- trimethoxybenzene was too long (13 steps with 3.5% overall yield) to practice. Finally, the authors improved and shortened the original synthetic route by application of Mgl2-assisted demethylation. 

Ishikawa, T. Oku, Y. Tanaka, T. Kumanoto, T. An approach to anti-HIV-1 active calophyllum coumarin s3mthesis An enantioselective construction of 2,3-dimethyl-4-chromanone ring by quinine-assisted intramolecular Michael-type addition. Tetrahedron Lett., 1999, 40 3777-3780. 

Quite recently, the use of natural cinchona alkaloids as catalysts for the intramolecular oxo-Michael addition of o-tigloylphenol (3), furnishing chiral ris-2,3-dimethyl-4-chromanone 4, which is a valuable intermediate for the synthesis of the anti-HIV-1 active coumarins, (+ )-calanolide A (5a), and (+ )-inophyllum B (5b), was reexamined by Ishikawa and coworkers (Scheme 9.2) [2], The parent cinchona alkaloids,... 

Synthesis of 2,2-dimethyl-4-chromanones 00JHC1389. Synthesis of 2,2-dimethyl-2H-chromenes 00H(53)1193. 

Chromanones. - One of the recently discovered minor constituents of hashish is a 5-hydroxychromanone called cannabichromanone (140), which was first identified by g.l.c.-m.s. The suggested structure has been confirmed by a synthesis of the compound from 2,2-dimethyl-5-hydroxy-7-pentylchromanone and methyl vinyl ether, a process which also produced varying amounts of the spiran (141), depending on the conditions. The chromanone (140) has no effect on the nervous system. 

Precocene II (125) and other chromenes have been synthesized and screened for their effect on the cloth moth. Precocene II has larvicidal properties. A trifluoro-compound (126), related to precocene, has been synthesized from 3,4-dimethoxyphenol, trifluoroacetone, and allylmagnesium bromide. Several natural chromenes, for example 6-acetyl-2,2-dimethyl-5-hydroxy-8-methoxy-2//-chromene, have been synthesized from the appropriate substituted 2-hydroxyacetophenone and either 2-methylbut-3-en-2-ol or 3-chloro-3-methylbut-l-yne. 2//-Chromenes are rarely prepared from chromanones, but a direct conversion of substituted 2,2-dimethylchromanones, e.g. (127), in high yield, into 2H-chromenes, e.g. (128), has been achieved by the action of PCls. °... 

Dimethyl-4-chromanones (34) were treated with hydrazoic acid in acetic acid (Schmidt reaction) to afford 2,3-dihydro-2,2-dimethyl-1,4-benzoxazepines (35) in good yields (Scheme 13) <92H(34)1523>. 

C-1,4-Phenyl migration. A soln. of 1 g. l,l,5,5-tetraphenyl-3,3-dimethyl-l-pentene in re/ r-butanol irradiated 10 hrs. with the Corex glass-filtered light of a 450 w. Hanovia medium-pressure lamp under deoxygenated Ng -> 150 mg. 1,4,5,5-tetraphenyl-3,3-dimethyl-l-pentene (and 760 mg. recovered startg. m.). H. E. Zimmerman and R. D. Little, Am. Soc. 96, 5143 (1974) C-phenyl migration in 3-chromanones s. A. Padwa and A. Au, Chem. Commun. 1975, 58. 

Obtained by hydrogenolysis of 7-hydroxy-8-isobutyryl-2,2-dimethyl-6,6-bis(3-methyl-2-butenyl)-5-(67/)-chromanone [24416-46-4] in ethanol over 5% Pd/C with hydrogen [8219]. 

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