Preparation of Polysubstituted Isochromanes by Addition of ortho-Lithiated Aryloxiranes to Enaminones

Abstract

The reaction of ortho-lithiated aryloxiranes with various enaminones straightforwardly affords new functionalized isochromanes as mixtures of two epimeric stereoisomers in reasonable to very good yields (50-90%). The two diastereomers, which show a high structural variability, can be easily separated by column chromatography.

Complexation Phenomena and Dynamics at Work in the Lithiation Reactions of Small‐Ring Heterocycles: Regio‐ and Stereoselectivity

“…There is no significant decomposition or isomerization of the intermediate oxiranyllithiums because of the short residence time and effective temperature control. [29] The synthetic utility of ortho-lithiated aryloxiranes, usually more conveniently generated by Li-Br exchange of the corresponding ortho-bromo derivatives, was proved by the reported synthesis of tetrahydronaphthols, [30] tetrahydroindenofuranones, [31] isochromanes, [32] phthalans, [33] oxazolinylaryl alkanones, [34] and 2,3-dihydro-10bH-oxazolo [2,3a]isoquinolines. [28b] The directed ortho metalation (DoM) reaction is nowadays recognized as a powerful and efficient method for regioselective functionalization of aromatic compounds.…”

“…Only in the lithiation reaction of trans-stilbene oxide, an α-vs. ortho competition was observed with the α/ortho ratio varying markedly with the employed experimental conditions. [29] The synthetic utility of ortho-lithiated aryloxiranes, usually more conveniently generated by Li-Br exchange of the corresponding ortho-bromo derivatives, was proved by the reported synthesis of tetrahydronaphthols, [30] tetrahydroindenofuranones, [31] isochromanes, [32] phthalans, [33] oxazolinylaryl alkanones, [34] and 2,3-dihydro-10bH-oxazolo [2,3a]isoquinolines. [35] sciences, and are also promising modules for drug discovery.…”

Toward Customized Tetrahydropyran Derivatives through Regioselective α‐Lithiation and Functionalization of 2‐Phenyltetrahydropyran

“…[5a] A novel one-pot multistep synthetic procedure for isochromane derivatives, on the basis of the addition of ortho-lithiated aryloxiranes to enaminones, was also reported. [6] However, despite advances in synthetic methodologies, direct functionalization processes of pre-existing THP nuclei remain challenging and rare. In this context, significant success was recently achieved by MacMillan and Jin, who developed an efficient photoredox-mediated α-arylation carbon-and heteroatom-based halides were found to be competent electrophiles for this transformation, as well as aliphatic and aromatic aldehydes and ketones, isocyanates, and carboxylic acid derivatives.…”

Ring Expansions of Oxiranes and Oxetanes

“…Professor Capriati has reported an interesting anionic cascade that employs aryl oxiranes containing ortho-bromides (Scheme 34) [48]. Lithium-halogen exchange results in the formation of an aryl anion, which adds in a conjugate addition fashion to enones containing a β-dialkylamino group.…”