Substituted-2H-chromenes

Finn [66] has reported that when alkenyl boronic acids are used in this process, the aminomethylphenol intermediates can undergo a further transformation to generate 2Ff-chromenes 153 (Scheme 7.20). This process can be done efficiently with catalytic amounts of dibenzylamine or the corresponding polymer-supported amine 154 to afford a variety of substituted 2H-chromenes 155-159 in one step. 

It was shown in the laboratory of P.T. Kaye that the reactions of 2-hydroxybenzaldehydes and 2-hydroxy-1-naphthaldehydes with various activated aikenes proceeded with regioseiective cyclization under Baylis-Hillman conditions to afford the corresponding 3-substituted 2H-chromene derivatives in high yields. Previous attempts to prepare 2H-chromenes chemoselectively via the cyclization of 2-hydroxybenzaldehyde-derived Baylis-Hillman products had proven unsuccessful. Complex mixtures containing coumarin and chromene derivatives were obtained. Good results were observed after the careful and systematic study of the various reactants and reaction conditions. 

Kaye, P. T., Nocanda, X. W. A convenient general synthesis of 3-substituted 2H-chromene derivatives. J. Chem. Soc., Perkin Trans, 1 2002, 1318-1323. 

In the case of 2,3-benzofuran (55), a stereoselective ring opening lithiation takes place under the same reaction conditions as for 2,3-dihydrobenzofuran (47) shown in Scheme 13, yielding the (Z)-organolithium intermediate (56) which, by reaction with different electrophiles and final acidic hydrolysis, gives the expected (Z)-products (57). The cyclization of the products obtained by reaction of intermediate (56) with carbonyl compounds under acidic conditions, affords the expected substituted 2H-chromenes (58) (Scheme 15) (01EJ02809). 

On the basis of aU the experimental results, an acceptable mechanism for the synthesis of 5-methylmercaptothio-carbonyl-4-aryl-3,4-dihydropyrimidin-2(l//)-ones 53 and substituted 2H-chromen-2-thiones 55 is disclosed in... 

Chromene, 2-morpholino-3-phenyl-synthesis, 3, 750 Chromene, 3-phenyl-2-substituted synthesis, 3, 756 2H-Chromene, 6-acetyl-... 

There has been a number of developments in the use of salicylaldehydes as precursors of both chromenes and chromans. Alkenes activated by acyl, formyl, nitrile and phenylsulfonyl groups react with 2-hydroxybenzaldehydes and 2-hydroxy-1-naphthaldehyde under Bayliss-Hillman conditions to yield 3-substituted chromenes via the in situ dehydration of the initially formed chroman-4-ol <02JCS(P1)1318>. In like manner, P-nitrostyrenes yield 2- and 2,2-substituted derivatives of 3-nitrochromenes <02H(57)1033>. A simple route to 2-phenyl-2H-chromenes starting from salicylaldehyde and utilising a Pd(0)-catalysed cyclisation of an allylic acetate has been described <02SC3667>. 

In addition to the aromatic multiplet, the spectrum of 2H-chromene (4) exhibits a quartet at 8 4.53 (2-CH2) and peaks at 5.38 (3-H) and 6.20 (4-H) (Figure 1). The last peaks are particularly significant, appearing in a variety of multiplet structures, the nature of which depends on the substitution pattern. However, the benzylic proton always appears downfield of H-3. Alkyl-substitution at C-2 causes an upheld shift of both alkenic protons, but disubstitution results in shifts to lower held. In the widely occurring 2,2-dimethylchrom-... 

H-Chromenes. Heterocyclic annulation that unite phenols and P-substituted acroleins is favorably mediated by PhBfOH). The method is characterized by the mildness of conditions and high efficiency in comparison with those involving other Lewis acids and bases. 

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. °... 

Diastereoselective synthesis of 2-substituted 2E/-chromenes result from metalloradical coupling-cyclization reactions of Al-tosylhydrazones with terminal alkynes mediated by cobalt(II) complexes of porphyrins (14JA1090). Cyclopropenes readily rmdergo a rhodium(III)-catalyzed C-H aaivation with N-phenoxyacetamides to produce 2,2-disubstituted 2H-chromenes in moderate-to-excellent yields (Scheme 16) (14AGE13234). 

A similar chemistry was disclosed in a patent appHcation from Guangzhou Institutes of Biomedidne and Health (15CN104860914) where a series of SFs-substituted chromenes was prepared and claimed as being effident and selective cyclooxygenase-2 (COX-2) inhibitors. Thus cyclocondensation of 4-SF5- or S-SFs-salicyhc aldehydes (116 or 114a) with ethyl 4,4,4-trifluorocrotonate provided racemic 7-SF5- or 6-SF5-2-CF3-2H-chromene-3-carboxylates ( )-117 and ( )-118, which were converted to the corresponding carboxyHc adds ( )-119 and ( )-113a (Scheme 31). 

Diverse dihydronaphtho[l,2-(r]furans were generated fix)m 1,4-naphthoquinones and olefins in the presence of ceric ammonium nitrate (13OBC6097). ( )-Lantalucratins A and B were produced in the presence of diammonium cerium(IV) nitrate (13T10470).Benzo[(>]furan moieties were synthesized by a three-component Mannich reaction of 3-acetyl-2H-chromen-2-one or l-(l-benzo[fc]fioran-2-yl) ethanone with p-substituted aromatic aldehydes and aromatic amines with ceric ammonium nitrate (CAN) as a catalyst (13MCR4787).p-Alkenylphenols went through the oxidative dimerization to generate substituted dihydrobenzo[l)]furans in the presence of CAN (13T653). 

A wide range of 4-thio-substituted 2-aryl-4H-chromenes is formed when 2-hydroxychalcone derivatives react with various thiols (Scheme 27). Two new C-S and C-O bonds are formed in this catalyst-free domino reaction (13T2430). Chiral phosphoric acids catalyze the photocyclization reduction of 2-hydroxychalcones (13CEJ13658) and the 1,4-reduction of racemic 2,4-diaryl-2H-chromen-2-ols (13CEJ9775), both in the presence of the Hantzsch ester, to provide 2,4-diaryl-4H-chromenes in good yields and with excellent enantioselectivity. 

Finn also showed the formation of 2H-chromenes under the same reaction conditions, using alkenylboronic acids and morpholine in dioxane at 90 °C. A more convenient route to the 2H-chromenes was then developed using a catalytic amount of dibenzylamine in the presence of alkenylboronic adds and salicylaldehyde (42, Scheme 7.11) [30]. Chromenes 43 were reported to arise from the initial Petasis borono-Mannich adducts 44 via an add promoted intramolecular S 2 attack of the ortho-hydroxyl group onto the protonated allylic amine of intermediate 45. A more likely mechanism involves elimination from 45 to intermediate 46, followed by 6n-electrocychzation to the product The reaction is tolerant of various functional groups and substitution patterns on the salicylaldehyde, and could also be promoted using a polymer-supported base, such as Merrifield resin-supported dibenzylamine (40-50 mol%) [30]. 

The 2H-chromene system, especially the 2,2-dimethyl-substituted derivative, is a constituent of numerous natural products, such as evodionol (12) and lapachenol (13), which occur in plants, and precocene I/ll (14), a juvenile hormone antagonist. 

Ronad, P M. Hunashal, R. D. Darbhamalla, S. Maddi, V. S. Synthesis and evaluation of anti-inflammatory and analgesic activities of a novel series of substituted-N-(4-methyl-2-oxo-2H-chromen-7-yl)benzamides. Arzneim. Forsch. 2008,58, 641-646. 

Ronad, P Dharbamalla, S. Hunshal, R. Maddi, V. Synthesis of novel substituted 7-(benzylideneamino)-4-methyl-2H-chromen-2-one derivatives as anti-inflammatory and analgesic agents. Arch. Pharm. 2008,341, 696-700. 

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