2.2-dimethylchromene

Song and Roh investigated the epoxidation of compounds such as 2,2-dimethylchromene with a chiral Mn (salen) complex (Jacobsen catalyst) in a mixture of [BMIM][PFg] and CH2CI2 (1 4 v/v), using NaOCl as the oxidant (Scheme 5.2-12) [62]. 

The authors describe a clear enhancement of the catalyst activity by the addition of the ionic liquid even if the reaction medium consisted mainly of CH2CI2. In the presence of the ionic liquid, 86 % conversion of 2,2-dimethylchromene was observed after 2 h. Without the ionic liquid the same conversion was obtained only after 6 h. In both cases the enantiomeric excess was as high as 96 %. Moreover, the ionic catalyst solution could be reused several times after product extraction, although the conversion dropped from 83 % to 53 % after five recycles this was explained, according to the authors, by a slow degradation process of the Mn complex. 

Interest in enantioselective epoxidation continues and 2,2-dimethylchromenes appear to be particularly suitable substrates for the evaluation of the catalytic system <96JCS(P1)1757, 96SL1079, 96TL3895>. 

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

Dimethylchromene has also proven to be a useful substrate for the assessment of various transition metal complexes as epoxidation catalysts. Chiral Mn(III)-salen complexes are efficient <00CC615 00T417> and can be recycled when used in an ionic liquid <00CC837>. The enantioselective aziridination of a chromene has been achieved using a chiral biaryldiamine-derived catalyst (Scheme 22) <00JA7132>. 

Benzylidene derivatives of the enantiomers of 1,2-diaminocyclohexane are also excellent ligands for the Cu(I)-catalyzcd asymmetric aziridination of olefins with 64, but the enantioselectivities using acyclic alkenes were about the same as those using ligand (S, S )-6658. When (5, 5 )-bis-(2,4-dichlorobenzylidenediamino)cyclohexane [(S,S)-67] was employed with C.u(I) triflate, 6-cyano-2,2-dimethylchromene (68) was converted to (R,R) 69 in a 75% yield with an ee greater than 98%58. 

The Goldberg coupling between 5-acetylamino-2,2-dimethylchromene 84 and 5-bromo-2-methylanisole 85 followed by hydrolysis leads to the diarylamine 86, which on palladium(II)-mediated oxidative cyclization affords pyrayafoline A 87 [ 17] (Scheme 30). Starting from 7-acetylamino-2,2-dimethylchromene, the method has been applied to the synthesis of 0-methylpyrayafoline B [54]. 

Addition of 7-amino-2,2-dimethylchromene 107 to 2-methyl-1,4-benzoquinone 108 in acetic acid/water leads to the 2-arylamino-5-methyl-1,4-benzoquinone 109 in moderate yield (Scheme 34). Oxidative cyclization of compound 109 using a stoichiometric amount of palladium(II) acetate in acetic acid under reflux provides pyrayaquinone A 110 [42,132]. 

Acidic hydrolysis of 5-acetylamino-2,2-dimethylchromene 84, the precursor for the synthesis of pyrayafoline A 87 (cf. Scheme 30), gives 5-amino-2,2-di-... 

Boyd, D.R., Sharma, N.D., Boyle, R., Evans, T.A., Malone, J.E., McCombe, K.M., Dalton, H. and Chima, J., Chemical and enz3mie-catalysed syntheses of enantiopure epoxide and diol derivatives of chromene, 2,2-dimethylchromene, and 7-methoxy-2,2-dimethylchromene (pre-cocene-1). J. Chem. Soc. Perkin Trans. 1,1996, 1757. 

The electronic properties of chiral catalysts were examined. Condensation of the optically active 1,2-diphenylethylenediamine with appropriate C5(5 )-substituted terf-butyl salicylaldehyde derivatives followed by complexation with mangane-se(III) center led to the corresponding catalysts 12a-12e. Then three model substrates, 2,2-dimethylchromene, cA-(3-methylstyrene, and cA-2,2-dimethyl-3-hexene, were subjected to enantioselective expoxidation catalyzed by 5-substituted... 

Hydroxyphenyl)-5-methoxy-6-(3,3-dimethylallyl)-2",2"-dimethylchromene-(5",6" 8,7)-3-(propyl-2-one)-47T-l-benzo-2,3-dihydropyran-2,4-dione. 

The structures of the so-called 2,2-dimethylchromene and 2,2-diphenylchromene dimers have been much debated. In 1900 Manuelli257 discovered that the natural compound lapachenol, to which later258 the structure 60 was assigned, gave a dimeric product by treatment with acids. On the basis of a mechanistic suggestion of Woodward, Living-... 

The characteristic absorptions of the gem-dimethyl group at 1380-1360 cm-1, the aromatic ether (1270 and 1120 cm-1) and a band at 900 cm-1 are important for the detection of the 2,2-dimethylchromene entity in natural products. 

Molecular dimensions have been reported for the 2,2-dimethylchromene bromouliginosin B (156), a derivative of an antibiotic from Hypericum uliginosum (68JA4723). Crystallographic data are also available for the pyranobenzopyran dibromoeriostoic acid (157) (67AX(B)120). 

Fluoro-l,l-dimethoxy-3-methylbut-2-ene reacts smoothly with a number of phenols. Monohydric phenols containing either electron-releasing or electron-withdrawing substituents afford satisfactory yields of 3-fluoro-2,2-dimethylchromenes. The regioselectivity of this synthon appears to parallel that described above (80JHC1377). 

A variation on the above theme utilizes o-quinones as the benzenoid component (70AC(R)564). Reaction with 3,3-dimethylallyltriphenylphosphonium bromide affords 2,2-dimethylchromenes, again through an intermediate allide. 

The resin secreted by Cannabis indica and Cannabis sativa, varieties of hemp, is known variously as marijuana, hashish or bhang and is abused as a hallucinogenic drug. It appears however to have some beneficial properties and is currently under test as an antiemetic in cancer therapy. The secretion contains a number of interrelated oxygen heterocycles, some of which are shown in Scheme 281, which attempts to indicate their biosynthetic relationships (70MI22401). The cannabinoids are probably derived from a monoterpene unit based on p-menthane and 5-n-pentylresorcinol (olivetol), acting the part of a polyketide. 2,2-Dimethylchromene biosynthesis also requires the intervention of an isoprene fragment. 

Examples of photochemically induced im electrocyclizations in oxygen-containing systems are relatively rare. 2//-Phenanthro[9,10-h]-pyran-4-carboxamides (16), for example, have been obtained in this way by irradiation of dienones (17).17 Similarly, the a-pyran (18) is formed on irradiation of ( )-//-ionone (19)18 a triplet excited state is believed to be involved and the reaction proceeds via the Z-isomer (20). The reverse process involving ring opening is more common and can lead to a wide variety of photochemically derived products. Thus, the products of irradiation of 2,2-dimethylchromene... 

These catalysts, 11-13, show good enantioselectivity ranging from 80 to 95% ee in the epoxidation of conjugated cfs-di- and tri-substituted olefins. Epoxidation of "good substrates such as 2,2-dimethylchromene derivatives proceeds with excellent enantioselectivity (>95% ee). Since the results obtained with these first-generation Mn-salen catalysts have been reviewed [21,33], only typical examples are shown in Table 6B.1. These reactions are usually carried out in the presence of donor ligand [34] such as 4-phenylpyridine A -oxide with terminal oxidants such as iodosylbenzene and sodium hypochlorite as described above. However, the use of some other terminal oxidants under well-optimized conditions expands the scope of the Mn-salen-... 

Aminobenzoyl)-5,7-dimethoxy-2,2-dimethylchromene (0.2 g) was dissolved in EtOH (30 ml) containing water (5 ml) and ammonium chloride (1 g) and Zn mossy (1.5 g) was added in portions and the mixture stirred at room temperature for 5 days. The solution was filtered, evaporated to dryness under reduced pressure and the residue dissolved in EtOAc (25 ml) and worked up in the usual way to give a solid (0.19 g). It crystallised from EtOH with MP 123°-126°C. 

Cyclization of aminodimethylchromenylbenzophenone 6-(2-aminobenzoyl)-5,7-dimethoxy-2,2-dimethylchromene (0.12 g) was dissolved in DMSO (8 ml) and NaH (0.06 g) added, the mixture was stirred for 6 days at room temperature. A further addition of NaH (0.06 g) was made and the solution heated to 50°C for 0.5 h whence it was poured into water, extracted with EtOAc and worked up in the usual way to give a crude mixture (0.11 g components). Separation of this mixture on plate (silica gel benzene EtOAc, 10 4) gave band 1 (Rf 0.45 38 mg) identified as starting material. Band 2 (Rf 0.32 42 mg 43%) which crystallized from ethylacetate as des-N-methylisoacronycine, MP 293°-295°C. Band 3 (Rf 0.10 29 mg, 29%) crystallized from ethyl acetate as des-N-methylacronycine. MP 237°-240°C. 

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