Mansonones, synthesis

The intramolecular Diels-Alder addition of a benzyne to a furan has been exploited in a synthesis of mansonone E (81TL4877). The benzyne (211), generated from the anthranilic acid (210), yields the adduct (212 86%) which is easily converted into the naphthalene (213 Scheme 79). A similar addition was achieved by generating the benzyne by treating an o -dibromobenzene with butyllithium. 

A facile peri-ring closure of dimethylnaphthol ether 1075 proceeds via ester hydrolysis and conversion to the corresponding acid halide followed by an intramolecular Friedel-Crafts acylation to afford the tricyclic chroman-3-one 1076, an intermediate during a formal synthesis of mansonone F (Equation 421) <2000CC1203>. 

Gerber has isolated (+ )-epicubenol (81) from a Streptomyces species. This compound is the enantiomer of that found in the essential oil of Cedrela toona Roxb. The syntheses of four naturally-occurring phenolic sesquiterpenoids obtained from the essential oil of elm wood have been reported, viz. (82 R = Me), (82 R = CHO), (83 R = Me), and (83 R = CHO). The known o-quinone, mansonone C (84), has also been isolated from elm wood. The structure (85) of sesquichamaenol, a minor component of the essential oil of Chamaecyparis forrnosensis, has been deduced on the basis of spectroscopic evidence and synthesis. Piers et al. have published complete details of their syntheses of a- and ) -cubebenes (86). 

Synthesis. - Cycloadditions. A bis-heteroannelation approach to ( )-ligularone (90) from (89) has been reported. Other intramolecular cycloadditions include the conversions of (91) into (92) and the intramolecular addition to the benzyne (93), which is the key to the synthesis of ( )-mansonone (94). ... 

Best and Wege59have reported the first total synthesis of Mansonone F and this is described in Scheme 10. Phenol (111)60 was made to react with 2-chloroacetyl-5-methylfuran (112) in dimethylsulfoxide and sodium methoxide to yield (113). Ketalization of (113) followed by catalytic reduction and basic hydrolysis afforded anthranilic acid (114). Diazotization followed by pyrolysis with propene oxide in 1,2-dichloroethane probably yielded aryne (115), which undergoes intramolecular Diels-Alder reaction producing the adduct (116). Deoxygenation and then acid hydrolysis afforded the product (117). This was subjected to Grignard reaction. The resulting tertiary alcohol on nitration yielded the nitro compound (118) which was subjected to reduction and oxidation respectively to obtain (119). It yielded Mansonone F (120) on dehydration. 

Suh et al.65 have reported a formal total synthesis of Mansonone F and this is described in Scheme 12. 5-Methoxy-a-tetralone (127) was converted to 1-methyl-5-hydroxy-naphthalene (128) by the standard organic reactions. Treatment of (128) with phenyl boronic acid, paraformaldehyde and propionic acid followed by catalytic hydrogenation yielded compound (129). This on alkylation gave the compound (130) which on alkaline hydrolysis was converted to acid. The acid halide underwent intramolecular Friedal-Crafts acylation affording an intermediate (131) whose transformation to Mansonone F has been accomplished by Best and Wege.59... 

Baneijee et al.66 have developed an alternative synthesis of the compound (129) whose utility in synthesis of Mansonone F (120) has been reported by Suh and collaborators.65 This is described in Scheme 13. Tetralone (127) was reduced with sodium borohydride to alcohol which on alkylation with benzyl chloride produced benzyl derivative (132). Its conversion to (133) was attempted by treatment with boron tribromide in dichloromethane. C ompound (133) (characterized b y m ass s pectroscopy) was obtained in poor yield. The major product was the diol (134), whose structure was confirmed by spectral data. It indicates that the demethylation was accompanied by debenzylation. Treatment of diol (134) with triethyl orthoformate and aluminium chloride afforded aldehyde (135) which was subjected to catalytic hydrogenation to produce compound (136). It was transformed to ketone (137) by oxidation and then made to react with methylmagnesium bromide in ether. The resulting tertiary alcohol on heating with p-toluenesulfonic acid in toluene for 24 hr produced the naphthalene (129) in 78% yield. 

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