Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

Abstract

The 1,2-aminoalcohol motif is one of the most prevalent structural components found in high-value organic molecules including pharmaceuticals and natural products. Generally, their preparation requires pre-functionalised substrates and manipulations of one functional group at a time to achieve the desired regioisomer. Herein, we describe a metal-free photosensitisation protocol for the installation of both amine and alcohol functionalities into alkene feedstocks in a single step. This approach is enabled by the identification of oxime carbonate as a suitable bifunctional source of both oxygen-and nitrogen-centred radicals for addition across alkenes with complementary regioselectivity compared to Sharpless aminohydroxylation. Use of orthogonal protection for amine and alcohol functionalities enables direct synthetic diversifications of one functional handle without influencing the other. With the use of readily available starting materials, convergent synthesis and mild reaction conditions, this process is well suited for use in various synthetic endeavors.The vicinal aminoalcohol motif is one of the most abundant structural units in natural products, pharmaceuticals, agrochemicals and privileged ligands. [1][2][3] Synthetic routes to this motif rely typically on multistep, iterative manipulations of functional groups to introduce both amine and alcohol functionalities in their desired positions. [4][5][6] Usually transition metal-catalysed directed β-C-H functionalisation of alcohols or amines offers a synthetic alternative with the necessity of a preinstalled directing group. [7][8][9][10] Nevertheless, all these approaches involve manipulation of one functional group at a time (Fig. 1a). By comparison, aminohydroxylation of alkenes is the most straightforward yet powerful approach for the synthesis of 1-amino-2-alcohols allowing simultaneous introduction of both functionalities into the molecule in a single step, as pioneered by Sharpless. 11,12 The generality of this approach however is often plagued by poor regioselectivity and the need for N-haloamides. 13 The use of a similar concept to synthesise 2-amino-1-alcohol skeleton requires a complete regioselectivity switch and remains a challenge to date (Fig. 1b). 14,15 So far, transient N-centred radical initiated aminohydroxylation strategy has been exploited in different intramolecular cyclisation context through ingenious substrate design to generate 2-amino-1-alcohol framework. [16][17][18][19] Clearly, lack of substrate generality and intramolecular nature of these transformations obviates there widespread use. In this regard, Yoon has elegantly utilized high strain of oxaziridine ring in aminal synthesis with analogous regioselectivity. [20][21][22] However, the requirement for initial radical attack by the alkene substrate to the copper-activated oxaziridine limits the use of unactivated alkenes in this aminohydroxylation approach. Alternatively, a two-step aziridination of alkene followed by nucleophilic ring opening can also deliver a similar regiosel...

Photocatalytic Anti‐Markovnikov Radical Hydro‐ and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

“…As shown in Scheme 3, both unactivated alkenes and styrenes were well suitable for this transformation ( 3 a – 3 l ). During this study, a similar photochemical method for the anti ‐Markovnikov olefin aminooxygenation was reported by Glorious and co‐workers [13] . The present protocol is comparable to the reported one in terms of efficacy and scope.…”

“…Chemie photochemical method for the anti-Markovnikov olefin aminooxygenation was reported by Glorious and co-workers. [13] Thepresent protocol is comparable to the reported one in terms of efficacya nd scope.…”

Photocatalytic Anti‐Markovnikov Radical Hydro‐ and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

“…Chemie Forschungsartikel 22170 www.angewandte.de photochemical method for the anti-Markovnikov olefin aminooxygenation was reported by Glorious and co-workers. [13] Thepresent protocol is comparable to the reported one in terms of efficacya nd scope.…”

Electrochemically driven stereoselective approach to syn-1,2-diol derivatives from vinylarenes and DMF

“…We note that this retention of diastereoselectivity upon choice of the stereoisomeric starting materials is unusual compared to previous examples that employ different alkene oxidation strategies. 12 …”