An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode

Abstract

We report the application of a chiral triazole-substituted iodoarene in a direct enantioselective hydroxylation of alkyl arenes. This method allows the rapid synthesis of chiral benzyl alcohols in high yields and exceptional stereocontrol despite its non-templated nature. In a unique cascade activation comprising of an initial irradiation-induced radical C-Hbromination and a consecutive enantioconvergent hydroxylation, the iodoarene catalyst has a dual role. It initiates the radical bromination in its oxidized state through an in situ formed bromoiodane and in the second, Cu-catalyzed step, it acts as a chiral ligand. To the best of our knowledge this the first example demonstrating the ability of a chiral aryl iodide catalyst acting both, as an oxidant and as a chiral ligand in a highly enantioselective C-H-activating transformation. Furthermore, this is the first example for an enantioconvergent hydroxylation. zylic C-H-bond in the presence tertiary C-H-bonds was observed. This unique reaction cascade offers great potential for other enantioselective oxidative benzylic C-H-activations, although the mechanism of the enantioconvergent step still needs to be further elaborated. ASSOCIATED CONTENTSupporting Information. The Supporting Information is available free of charge on the ACS Publications website at DOI: XXX. Including all experimental procedures and characterization data.

N‐Heterocyclic Iod(az)olium Salts – Potent Halogen‐Bond Donors in Organocatalysis

“…In this regard, we recently introduced N‐heterocycle‐stabilized iodanes (NHIs) and found a remarkable reactivity of these reagents which outcompetes well known iodanes in a plethora of oxidative couplings ‐ even in catalytic applications (Figure 2a) [42,43] . We also developed chiral N‐heterocycle‐substituted iodoarenes as chiral iodane precursors and applied them in a plethora of highly enantioselective couplings (Figure 2b) [44,45] . Very recently, we were able to introduce iodolopyrazolium salts as a unique class of N‐heterocycle‐based iodolium salts [46] .…”

“…[ 42 , 43 ] We also developed chiral N‐heterocycle‐substituted iodoarenes as chiral iodane precursors and applied them in a plethora of highly enantioselective couplings (Figure 2 b). [ 44 , 45 ] Very recently, we were able to introduce iodolopyrazolium salts as a unique class of N‐heterocycle‐based iodolium salts. [46] In our initial report, we demonstrated their potential reactivity as XB‐donors.…”

Stereoselective Oxidative Cyclization of N-Allyl Benzamides to Oxazolines

“…A chiral aryl iodide is formed, which can be re-oxidized using an external oxidant. [38][39][40][41][42][43][44][45][46][47][48][49][50][51] This general method has been applied by Moran and co-workers using a well-established resorcinolbased chiral iodoarene catalyst, 52 53 53-57 but unfortunately with only modest results, in particular regarding stereoselectivity and substrate scope, with a focus on 6-membered N-heterocycles. 24 Scheme 2.…”

“…Our group recently established chiral triazole-substituted iodoarenes 1 and applied them in a wide range of enantioselective oxidative transformations (Figure 2). 49,50,58 In this article we want to report their further application to the as-yet underexplored oxidative cyclization of N-allyl amides.…”

A Catalytic Highly Enantioselective Synthesis of Spirooxazolines

“…23 Our group recently developed chiral triazole-substituted iodoarenes, and successfully applied these chiral C1-symmetric iodoarene catalysts in a plethora of oxidative enantioselective transformations such as α-oxytosylations, (spiro)lactonizations, rearrangements and benzylic hydroxylations. 21,24 Intrigued by their high reactivity, we wondered whether these omnipotent catalysts can be applied in the yet underexplored generation of spirooxazolines through an oxidiative spirocyclization of suitable substrates. We started our investigations using N-((2-hydroxynaphthalen-1-yl)methyl)benzamide 4a as the model compound (Table 1).…”