1 //-isochromene derivatives

Banfi L, Basso A, Casuscelli F, Guanti G, Naz F, Riva R, Zito P (2010) Synthesis of novel isochromene derivatives by tandem Ugi Reaction/nucleophilic substitution. Synlett 85-88... 

Hashmi et al. also applied gold catalysis to the isochromene derivatives. This paper also reported a benzylic C-H activation that provided unprecedented dimerization from the formation of eight new bonds [110]. 

This polycyclic 2-benzopyrylium salt was also obtained in good yield from the 2-benzopyrylium salt 56, through intramolecular acylation of the intermediate isochromene derivative 60. The same approach was used later by Elliott and co-workers (84CJC2435) in the synthesis of some benzofc]-phenanthridine analogs. 

Alkynylbenzaldehydes cyclize in the presence of bis(pyridine)iodonium tetrafluoroborate (IPy2BF4) to form the intermediate 4-iodoisochromenylium species 141, which can be trapped by various nucleophiles to afford 4-iodo-l//-isochromene derivatives (Scheme 45) <2003JA9028>. 

Han X, Zhong Q, Yue D, Della Ca N, Larock RC, Armstrong DW (2005) Separation of enantiomers of isochromene derivatives by HPLC using cyclodextrin based stationary phases. Chromatographia 61 205-211... 

The transformation of ort/zo-alkynylaryl ketones (275) to isochromene derivatives (276) through a cyclisation/enantioselective-reduction sequence has been realised in the presence of a chiral silver phosphate catalyst (277). The reaction afforded the li -isochromene derivatives (276) in high yield with fairly good to high enantioselectivity (Scheme 75). ... 

Recently, Ackermann and coworkers reported aliphatic hydroxyl-directed oxidative annulation reactions of benzyl alcohols with alkynes to form isochromene derivatives (Eq. (7.11)) [16]. This C-H/O-H functionalization process performed smoothly by using [RuCl2(/ -cymene)]2 (5 mol%)/AgPFg (20 mol%) as catalyst and Cu(OAc)2 H2O (20 mol%) as oxidant under an atmosphere of air. Various tertiary benzylic alcohols, a,a-dimethylallyl alcohol, and diverse internal alkynes are appropriate substrates for this transformation. The reaction occurred with moderate to high regioselectivity for unsymmetrical alkylarylacetylene, and an irreversible C-H metalation step is involved in the catalytic cycle. 

A gold-catalyzed benzylic C-H functionalization for the synthesis of IH-isochromene derivatives 34 was disclosed by Hashmi and coworkers in their study of the intramolecular hydroalkoxylation of alkynes (Scheme 12.15) [19]. A proposed mechanism for this reaction is shown in Scheme 12.16. The reaction... 

In contrast with the reaction of 4-yn-l-ols, both 6-endo-dig and 5-exo-dig cyclization modes were observed in the Pdl2/KI-catalyzed oxidative car-bonylation of2-(l-alkynylbenzyl)alcohols (Eq. 43) [120]. The preferential formation of the lH-isochromene or the 1,3-dihydroisobenzofuran derivative turned out to be dependent on the substitution pattern of the substrate. In particular, lH-isochromenes were obtained as the main reaction products when the triple bond was substituted with an alkyl group and with a primary alcoholic group, while the isobenzofurans were preferentially formed with a tertiary alcoholic group and when the triple bond was terminal or conjugated with a phenyl group. 

The monophosphonium salt derived from l,2-di(bromomethyl)benzene reacts with sodium carboxylates to afford high yields of the ester (190). Generation of the ylide results in spontaneous cyclization via an intramolecular Wittig reaction to the isochromene (Scheme 35) (79TL2149). 

Oxidation of l-(3-allylnaphthalen-2-yl)ethanol derivative 132 under Wacker oxidation conditions gives 5-(benzyloxy)-7,9-dimcthoxy-l,3-dimethyl-l//-bcnzo[g isochromene in excellent yield (Equation 62) <20040BC2461>. 

Allylbenzyl alcohols 133 can cyclize to their corresponding isochromenes under palladium(ll) catalysis in moderate yield (Equation 63) <1999TL4871>. Similarly, ( )-(2-hydroxymethyl)styrene derivatives 134 undergo intramolecular cyclization under palladium(ll) catalysis to afford isochromenes (Equation 64) <1999TL4871>. 

Vinyl-l//-isochromenes can be prepared in moderate yield by a palladium-catalyzed coupling of ( )-(3-(2-bromo-phenyl)allyloxy)tenM)i i r l)si Iyl derivatives 157 with ketones. The reaction proceeds via initial ketone arylation to furnish the intermediate 158 followed by intramolecular cyclization of the ketone enolate onto the tethered allylic system (Scheme 50) <2000CG1675>. 

The addition of hypochlorous acid to the 3,4-position of the isoquinoline Reissert compound (2 R = Ph) takes place to give the chlorohydrin 71." Use of A -chlorosuccinimide in ethanolic dioxane gave the 0-ethyl derivative. Various reactions of the chlorohydrin led to isochromenes and a rearranged isoquinoline." ... 

Li has reported the water-promoted, gold(I)-catalyzed cascade addition/cyclization of terminal alkynes with o-alkynylbenzaldehyde derivatives to form 1-alkynyl-lH-isochromenes [41]. For example, reaction of l-(2-phenylethynyl)benzaldehyde with phenylacetylene catalyzed by a 1 4 mixture of (PMe3)AuCl and Hunig s base in a water/toluene mixture at 70 °C for 1 day led to isolation of isochromene 29 in 81% yield (Fq. (12.11)). The transformation is presumably initiated by gold-catalyzed addition of acetylide to the C=0 bond of the aldehyde moiety followed by addition of the resulting alkoxide across the pendant C=C triple bond. 

X.-S. Wang, J.-R. Wu, J. Zhou, S.-J. Tu, J. Comb. Chem. 2009, 11, 1011-1022. Green method for the synthesis of highly substituted cyclohexa-1,3-diene, polyhydroindene, polyhydronaphthalene, isochromene, isothiochromene, and isoquinoline derivatives in ionic liquids. 

Intramolecular alkoxymetalation of alkenes is one of the efficient methods to prepare cyclic ethers. He and co workers have reported that silver (I) triflate catalyzes the intramolecular addition of alcohols to olefins [26]. The reaction of 2,2-diphenyl-4-hexen-l-ol (16) under the influence of 5 mol% of the silver(I) catalyst affords a 10 1 mixture of tetrahydrofuran derivative (17) and tetrahydropyran derivative (18) in high combined yield (Scheme 18.6). In the case of terminal disubstituted y-hydroxyl alkenes, 6-endo cyclization products are formed exclusively. This procedure has been successfully expanded to cyclization of pent-4-enoic acid, hex-5-enoic acid, and their derivatives leading to the corresponding lactones [26]. Using similar cyclization methods catalyzed by silver(I) compounds, 1-allenyl isochromenes [27], dihydrobenzofurans [28], and dihydrobenzopyrans [28] have been synthesized. 

Heterocyclic compounds containing oxygen include many phenolic compounds, particularly flavonoids, the most important pigments of which are anthocyanins related to pigments derived from isochromene and xanthone. 

The main chromophore of isochromenes arises as a hexaketide from activated forms of acetic and malonic acids and the side chain of pigments is derived from 2-oxohexanic and 2-oxooctanoic acids that are synthesised analogously to other fatty acids. 

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