Oxidatively generated electrophiles as initiators of epoxide cascade cyclization processes

Oxidatively generated oxocarbenium ions are shown to be effective promoters of polyepoxide cascade cyclization reactions to form polyether compounds. The reaction conditions are neutral, ensuring that background acid-mediated processes are not operative and that other acid-sensitive functional groups, such as acetals, can be incorporated into cyclization substrates. While 5-exo pathways are more common that 6-endo pathways, a rational design has been employed to access tetrahydropyranyl ethers.

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(R)-2-Ethoxy-2-((2S,5S)-tetrahydro-5-((R)-tetrahydro-5-(octyloxy)furan-2-yl)furan-2-yl)ethanolC20H38O5[α]D25=-8.5 (c 0.30, EtOAc)Source: asymmetric synthesis

(2S,3R,4S,6R)-3-(4-(Trifluoromethyl)benzyloxy)tetrahydro-6-methoxy-2-methyl-2H-pyran-4-olC15H17F3O4[α]D25=-129.3 (c 0.18, EtOAc)Source: asymmetric synthesis

(S)-2-Ethoxy-2-((2R,5S)-tetrahydro-5-((R)-tetrahydro-5-(octyloxy)furan-2-yl)furan-2-yl)ethanolC20H38O5[α]D25=-3.8 (c −0.45, EtOAc)Source: asymmetric synthesis