Efficient Enantioselective Synthesis of Oxahelicenes Using Redox/Acid Cooperative Catalysts

Abstract

An efficient and enantioselective synthesis of oxa[9]helicenes has been established via vanadium(V)-catalyzed oxidative coupling/intramolecular cyclization of polycyclic phenols. A newly developed vanadium complex cooperatively functions as both a redox and Lewis acid catalyst to promote the present sequential reaction and afford oxa[9]helicenes in good yields with up to 94% ee.

Symmetric, Unsymmetrical, and Asymmetric [7]‐, [10]‐, and [13]Helicenes

“…Recently the transition‐metal‐mediated [2+2+2]‐cycloisomerization has been utilized for the synthesis of long helicenoids that have regions of linear annulation being part of the helical backbone, as in 3 , or the inclusion of 2H ‐pyranes as in oxa[19]helicenoid ( 4 ) . Using furan formation as the annulating step allows for the convenient preparation of oxa[ n ]helicenes, such as 5 and 6 . Herein we describe how an annulative π extension (APEX) benzofuran scaffolding, between 3,6‐dihydroxy‐carbazoles ( 7 ) and 2‐naphthols ( 8 ), allows us to construct long heterocyclic helicenes: diazaoxa[7]‐, diazadioxa[10]‐, and diazatrioxa[13]helicenes ( 9 – 11 ; Figure b).…”

“…Removal of the resolving agent, followed by methylation provided the optically pure [13]helicenes ((+)‐ 25 and (−)‐ 25 , ee =99 % for both enantiomers, see the Supporting Information, Figure S1). To the best of our knowledge, these are the longest optically pure helicenes which have synthetically been prepared . Heating (+)‐ 25 at 200 °C in diphenylether for 4 h, no racemization was observed (Supporting Information, Figure S2).…”

“…[17][18][19] Using furan formation as the annulating step allows for the convenient preparation of oxa[n]helicenes,such as 5 and 6. [20,21] Herein we describe how an annulative p extension (APEX) benzofuran scaffolding, between 3,6-dihydroxy-carbazoles (7)a nd 2-naphthols (8), allows us to construct long heterocyclic helicenes:d iazaoxa-[7]-, diazadioxa[10]-, and diazatrioxa [13]helicenes (9-11;F igure 1b). We demonstrate how the synthetic method allows the preparation of symmetric,u nsymmetrical, and asymmetric (chiral) [13]helicenes,h ow the [13]helicenes can be resolved into its enantiomers,and how we can introduce functionalities at the ends and the periphery.…”

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…The reaction proceeds via oxidative coupling at first, followed by intramolecular cyclization. This results in the one-step enantioselective synthesis of oxa [9]helicenes in good yields with up to 94% ee [111] (Scheme 36). In 2015, a new general asymmetric synthetic methodology was successfully developed for [5]-, [6]-, and [7]helicenes with ultimate enantioselectivity (ee >99) based on the controlled transfer of reactant point chirality to the product with unidirectional helicity [112].…”

“…The reaction proceeds via oxidative coupling at first, followed by intramolecular cyclization. This results in the one-step enantioselective synthesis of oxa [9]helicenes in good yields with up to 94% ee [111] (Scheme 36). Besides the optical resolution of racemates, another approach to enantiopure helicenes is based on the stereospecific synthesis, where the originally chiral precursors or reagents are converted into the corresponding helicenes with unidirectional helicity [110].…”