Epoxidation of 2,2-dimethylchromenes

As a solvent for the asymmetric epoxidation of 2,2-dimethylchromene mediated by Jacobsen s chiral (salen)-manganese catalyst.49... 

Scheme 5.6 Epoxidation of 2,2-dimethylchromene with a chiral manganese-salen catalyst...

Substrate Scope. Best results in the (salen)Mn -catalyzed epoxidation reaction have been obtained with cis-disubstituted, conjugated alkenes (Table 1). Epoxidation of 2,2-dimethylchromene derivatives occurs with especially high selectivity (>97% ee). frans-Disubstituted alkenes are epoxidized with low selectivity (20-50% ee), as are simple alkyl-substituted alkenes. 

The prevalence of 2,2-dimethylchromene derivatives (arising biosynthetically via addition of an isoprene unit to phenols) in a variety of natural products led to extensive examination of the asymmetric epoxidation of numerous such substrates, the yields and enantioselectivies of the thus-obtained fused oxiranes typically being good to excellent <1991JA7063, 1991TL5055, 1993SL261, 1995TL5457>. 

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>. 

The group of Wang has prepared a series of Mn(salen) complexes containing a pyrrolidine backbone (49, Figure 9) 6-nitro- and 6-cyano-2,2-dimethylchromene are epoxidized in 86-99% yield and 86-96% ee <2006JCT248>. 

Many 2,2-dimethylchromenes (131) are oxidized (in 32—11% yield) by T1(N03)2 in MeOH to the dihydrobenzofurans (132). The naturally occurring compound precocene I (133) gave the epoxide (134) upon treatment with NBS and NaH. The epoxide is readily cleaved, and may have a role in the termination of the production of juvenile hormone in some insects. The ease with which the double-bond of the pyran is reduced in 4-aryl-2/f-chromenes varies according to whether the 4-aryl group also has a nitro-group, because the amine that is then formed increases the pH of the medium. This effect can be offset by... 

Methoxy-2,2-dimethylchromene (23.6) and benzofuran 23.2 were also synthesized by alkylation of 4-methoxyphenol to 2-(3-methyl-2-butenyl)-4-methoxyphenol (22.1) followed by acid catalyzed cyclization of the corresponding epoxide 22.2 to a mixture of isomeric compounds 23.3 and 23.7. Dehydration of alcohol 23.7 with / -TsOH gave 23.6, while NBS dehydrogenation of 23.3 afforded 23.2 140). 

The Jacobsen-type manganese complex gives lower yields of epoxides (40-60%), but for 2,2-dimethylchromene and styrene the epoxides are optically active (12-60% ee). 

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]. 

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>. 

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. 

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-... 

Catalyst ( Bu-4.33) is effective in the epoxidation of many ds-alkenes, such as the acyclic alkenes (4.42) and also cychc alkenes, especially 2,2-dimethylchromenes such as (4.43). Enhanced enantioselectivities are often observed using Katsuki s second generation catalysts (4.34) where the phenyl substituents of the BINAP moiety undergo greater steric interactions with the alkene substrate. Dihydronaphthalene (4.44) has been epoxidised with record ees using this catalyst system. ... 

Kureshy [198] had also carried AE with a poly-salen. The poly-salen 316 derived from chiral diphenylethylenediamine (2 mol%) (Scheme 132) and NaOCl in the presence of cooxidant (NMO, 4-PPNO, PyNO, DMSO) forming the oxidative reagent were used for the epoxidation of styrene, indene and 6-cyano-2,2-dimethylchromene. In all cases, the best results in term of... 

Freire and coworkers described the intercalation of a chiral phosphonic acid derivatised [Mn (sa/e )Cl] complex within KlO-Montmorillonite layers by ion-exchange with the interlayer potassium cations. The catalytic performance of the heterogeneous catalyst (denoted as [Mn (sa/en)Cl] K10) was evaluated in the enantioselective epoxidation of styrene, a-methylstyrene and 6-cyano-2,2-dimethylchromene, at 0 °C in dichloromethane or acetonitrile, using three different oxidant systems m-CPBA/NMO, PhIO and NaOCl the results are summarised in Table 11.1. 

Kureshy and coauthors [82] also reported that chiral Mn(Salen) catalyst immobilized in the nanopores of MCM-41 and SBA-15 (Scheme 10.14) showed higher enantioselectivity (70% ee) than its homogeneous counterpart (45% ee) for the enantioselective epoxidation of styrene with aqueous NaOCl as the oxidant. In addition, the immobilized chiral Mn(Salen) could smoothly catalyze the epoxidation of bulkier alkenes such as 6-cyano-2,2-dimethylchromene into their epoxides with enanatioselectivity (up to 92% ee) comparable to those of the homogeneous counterparts. The heterogeneous catalyst could be recycled four times without notable loss of activity and enantioselectivity. 

Kureshy s group [83] immobilized the Mn(Salen) catalyst axially in the nanopores of MCM-41 via pyridine N-oxide (Scheme 10.15). These immobilized catalysts showed higher enantioselectivity (69% ee) than their homogeneous counterparts (51% ee) for the asymmetric epoxidation of styrene and were also effective for the asymmetric epoxidation of bulkier substrates such as indene and 2,2-dimethylchromene (conversion 82-98% ee 69-92%). The catalysts could be recycled for at least four times without loss in performance. The increase in ee values was attributed to the unique spatial environment constituted by the chiral Salen ligand and the surface of the support. 

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