Intermolecular [3+2] Cycloaddition of Cyclopropylamines with Olefins by Visible‐Light Photocatalysis

Abstract

Solar energy is clean, abundant, and more importantly, renewable. As such, any reaction that efficiently harvests and converts solar energy into chemical energy is more important than ever as the world turns to its scientists to meet the challenge of environmental sustainability. Visible light (390-750 nm) accounts for 43% of the overall solar spectrum. However, many organic molecules are unable to absorb visible light efficiently, thereby limiting the use of visible light in organic synthesis. A possible solution to this problem involves the use of visible-light photoredox catalysts such as ruthenium [1] or iridium [2] polypyridyl complexes to channel energy from visible light into organic molecules. The groups of MacMillan, [3] Yoon, [4] Stephenson, [5] Akita, [6] and others [7] have recently published seminal works on visible-light-promoted C-C bond-formation reactions catalyzed by these complexes. Amines are often used as a sacrificial electron donor to reduce the photoexcited Ru II and Ir III complexes to Ru I and Ir II complexes. [8] Recently, amines have been also explored as a substrate in these processes. [9] We were intrigued by the potential of using amines as both the sacrificial donor and the substrate, thus making the process more atom economical.We envisioned a class of amines that are capable of initializing a downstream irreversible reaction upon oxidation by the photoexcited Ru II or Ir III complexes. Cyclopropylamines have been shown to undergo irreversible opening of the cyclopropyl ring upon their oxidation to the nitrogen radical cations. Based on this mode of action, cyclopropylamines have been used to probe amine oxidation in biological systems. [10] Cyclopropylamines have seen limited use in organic synthesis to date. [11] All these applications focus on intramolecular reactions, except the formation of the endoperoxides. [11a] Furthermore, the generation of nitrogen radical cations requires UV light with a photosensitizer or a strong oxidant (e.g., ceric ammonium nitrate), thus limiting the substrate scope and/or the type of the products being formed. Since visible-light photocatalysis has been shown to be a mild and chemoselective method to oxidize amines, we envisioned that new transformations of cyclopropylamines catalyzed by a Ru II or Ir III polypyridyl complex could be developed (Scheme 1). Herein we report an intermolecular [3+2] cycloaddition of olefins with monoand bicyclic cyclopropylanilines under visible light photocatalysis. ** We thank the University of Arkansas, the Arkansas Bioscience Institute, and the NIH NCRR COBRE grant (P30 RR031154) for generous support of this research. R.S.S thanks the Division of Organic Chemistry of the ACS for a SURF award. We also thank Prof. Bill Durham for insightful discussions on photochemistry and Prof. Jim Hinton for obtaining NOESY spectra.

Intermolecular [3+2] Annulation of Cyclopropylanilines with Alkynes, Enynes, and Diynes via Visible Light Photocatalysis

“…[5b] We were motived to examine more conditions in order to improve the yields, as shown in Table 1. Using the [3+2] annulation of cyclopropylaniline 1a with phenylacetylene 2a as the model reaction, we first investigated the annulation in a continuous flow format [6] (entry 2).…”

“…This ion presumably results from ring opening of cyclopropylanilines that is induced by one-electron oxidation of the parent amine by the excited state of Ru(bpz) 3 (PF 6 ) 2 . [5a] The use of TEMPO was designed to intercept the radical moiety of the ion and thereby perturb the annulation. Indeed, the annulation product was isolated in a negligible yield, which lent credence to our argument for the involvement of distonic ion 1a •+ .…”

“…We have recently developed a [3+2] annulation of cyclopropylanilines with alkenes and alkynes. [5] Although our preliminary results in these reactions gave a glimpse of their potential in DOS, constraints with respect to both reacting partners, cyclopropylanilines and alkenes or alkynes, existed. An aryl group was required on the cyclopropylamine moiety while only terminal alkenes and alkynes were reactive.…”

“…An aryl group was required on the cyclopropylamine moiety while only terminal alkenes and alkynes were reactive. [5] We intended to address both limitations with the ultimate goal of thoroughly investigating the scope of the [3+2] annulation. Herein we report our findings towards expansion of these reactions.…”

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…16 One recent result suggests that systems based on visible-light photocatalysis may also be applicable. 105,106 M A N U S C R I P T…”