4-Methylene-chromanes

Methylene chromans can be prepared by a palladium-catalyzed intramolecular cyclization of 2-iodophenyl alkynyl ethers 455. Simple modifications to the reaction conditions lead to either (E)- or (Z)-4-methylene chromans (Scheme 103) <2001TL2657>. 2-Iodophenyl alkynyl acetals are also viable substrates for this reaction <2005JOG489>. Addition of tris(2,6-diphenylbenzyl)tin hydride (TDTH) to a triethylborane-mediated intramolecular cyclization of 2-iodophenyl alkynyl ethers ensures complete (A)-selectivity is observed in the resulting 4-methylene chroman <2001AGE411>. 

In this work, we have studied the reaction of 4-hydroxycoumarin (67) and 3-(dimethylamino-methylene)chromane-2,4-dione (68) with aromatic binu-cleophilic compounds (Scheme 19). 

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 ... 

Monosubstituted allenes 510 can be successfully inserted into the oxapalladacycles 511 to afford regioisomeric chromans 512 and 513. Oxapalladacycles 511 bearing no substitution on the aromatic ring give a mixture of regioisomeric products, but w >-methylene chromans 512 are exclusively formed upon introduction of a substituent at C7 (Equation 212, Table 25) <2004JOC8266>. 

The Cr(II) promoted cyclisation of (2-iodopbenyl) alkynyl ethers catalysed by Ni(II) involves activation of the C-I bond and leads to the ejco-methylene chroman (94TL1601). 

These observations indicated that an intermolecular double condensation to give a bis N-(methylene-4-oxocoumarinyl)-l,4 aromatic diamine had occurred. Data from the elemental analysis indicated that the calculated and observed values were within the acceptable limits ( 0.4%) and in conformity with the assigned structure. In the addition of molar equivalents of 1,4-aromatic binucleophilic compounds to compound 72 we did not observe any heterocyclic compounds resulting from the further intermolecular nucleophilic attack on the single condensation product. Since the condensation of 3-(dimethylaminomethylene)-chromane-2,4-dione with aromatic binucleophilic compounds is the only route to the new coumarinic compounds, this represents a useful synthetic method. 

The I3C spectra of chroman-4-ones are similar to those of the corresponding chromone, although the C-2 and C-3 resonances occur at much higher field, as expected of methylene... 

The UV photoelectron spectra of several chromans have been compared with other cyclic and acyclic ethers. The chroman spectra are clearly distinguishable from those of the other ethers and the differences have been interpreted in terms of the decreased conjugative effects of oxygen and increased hyperconjugative effects of the 4-methylene group (76T167). 

The insertion of allenes into a stable oxapalladacycle yields chromans. Monosubstituted electron-rich allenes afford the 2,3-disubstituted 4-methylene derivative with high regiocontrol and complete diastereocontrol, whereas those containing an electron-withdrawing group give the 2-substituted 4-( )-ylidene compound (Scheme 8) <04JOC8266>. 

Glycoside formation followed by ring closure occurred with formation of a chroman in the reaction of the 3,4,6-tri-0-benzyl-2-C-acetoxymethylgalactal shown with 4-methylphenol in dichloromethane containing boron trifluoride-etherate at 0°C to afford the a-product in 70% yield by way of the C-2-methylene-O-glucoside which could be prepared separately and converted to the same pyranobenzopyran under similar conditions (ref. 38). 

Thiochromans and Thiochromones.—The spirothiochroman (175) has been synthesized from 3-methylene-l/7-2-benzothiopyran-4(3//)-one (176) and its stereochemistry has been examined, using X-ray crystallography. Modifications which have been made to Dianin s compound (see also under Chromans ) include replacement of the ring oxygen by sulphur. Some such compounds retain the clathrate-forming ability of the original molecule. 

Chiral ( )-crotylsilanes give tetrahydrofurans, cyclohexanones lead to spiro[4,51decane through a-(silylmethyl)divinyl ketone substitution, P-(alkoxycatbonyl)allylsilanes with epoxides give a-methylene-y-lactones fused to carbocycles, benzyl cations add to give tetrahydronaphthalenes or dihydro(lf/)indenes while tricyclic -2-phenyl-4H-1,3,2-benzodioxaborins with allylSiMes give polycyclic chromans l. 

---