A Triazole‐Substituted Aryl Iodide with Omnipotent Reactivity in Enantioselective Oxidations

Abstract

Aw idely applicable triazole-substituted chiral aryl iodide is described as catalyst for enantioselective oxidation reactions.The introduction of asubstituent in ortho-position to the iodide is key for its high reactivity and selectivity.B esides ar obust and modular synthesis,t he main advantage of this catalyst is the excellent performance in ap lethora of mechanistically diverse enantioselective transformations,s uch as spirocyclizations,p henol dearomatizations, a-oxygenations, and oxidative rearrangements.D FT-calculations of in situ generated [hydroxy(tosyloxy)iodo]arene isomers give an initial rational for the observed reactivity.Hypervalentiodinecompoundsareversatileoxidantswhich have been utilized with great success in aplethora of oxidative coupling reactions [1] and in natural product synthesis. [2] In related enantioselective processes,achiral aryl iodide precursor can be used in catalytic amounts in combination with aterminal co-oxidant to generate achiral hypervalent iodine compound in situ. This chiral oxidant is subsequently capable of transferring its chirality onto the desired coupling products through diastereotopic transition states in the key oxidative C-X bond forming step. [3] Since the discovery of the first enantioselective transformation catalyzed by ac hiral aryl iodide in 2007 by Wirth and co-workers, [4] more than ad ozen highly diverse C1-and C2-symmetric chiral aryl iodides have been developed. [5] Successful catalysts,s uch as 1-4 ( Figure 1), usually show ag ood reactivity and selectivity in only one distinct class of oxidative transformation. So far there is no omnipotent chiral aryl iodide available that performs well throughout the most important oxidative transformations and hence can be seen as broadly applicable catalyst for iodane-based enantioselective couplings.Our group is heavily interested in the development of N-heterocycle-stabilized iodanes (NHIs) as an ew class of stable and at the same time highly reactive hypervalent iodine compounds. [6, 7] With the aim to design novel chiral aryl iodides which are robust to synthesize in amodular sequence and show ag ood performance throughout adiverse range of enantioselective oxidations,w erecently developed the novel triazole-substituted aryl iodide 5 ( Figure 2) and evaluated its reactivity in the Kita-spirocyclization of 1-naphthols. [8] Even though this "first-generation" catalyst gave the so far highest enantioselectivities in direct comparison to other C1-symmetric aryl iodides for this reaction, reactivities were low.W ell-established C2-symmetric aryl iodides,s uch as spirobiindanes developed by Kita or resorcinol ethers 1 developed by Uyanik and Ishihara, showed significantly higher stereoinduction and yielded the desired chiral lactones in better yields. [9] Due to the promising initial results with catalyst 5 and its highly modular and robust synthesis,w e further developed "second-generation" triazole catalysts 6 ( Figure 2) bearing as imple ortho-modification at the aryl iodide.W et herefore synthesized orth...

λ3‐ and λ5‐Iodanes: Substituent Effects and Pseudorotation/Hypervalent Twisting

“…For example, the second‐generation precatalyst 100 a , employed for asymmetric dearomatization of bromo‐substituted cresol 101 afforded to the desired product 102 in 92% yield and 93% ee (Scheme 21). [125] Enantioselectivity was found to be the best, superseding the previous results [127] with indanol‐based iodo‐arene‐precatalyst (up to 84% ee ).…”

“…The energies of the isomers of unsubstituted iodanes 103a – d were found to be in the order of 103b < 103a < 103c < 103d , while for 104a – d , the order was found to be 104c < 104d < 104a < 104b (Figure 14). The structure 103b with the lowest energy among 103a – d displayed a dihedral angle of 11.0° [125] . On the other hand, the structure 104c was found to be the most stable among 104a – d , where a dihedral angle of 93.86° was found.…”

“…The hypervalent iodine here can be stabilized through nitrogen or oxygen atom of the triazole and O‐TMS group, respectively. Calculations showed that the isomers 103a and 103b have similar energy, whereas 104a with N−I stabilization was found to be more stable than 104b by ∼3.81 kcal/mol, Figure 14 [125] . In these cases, the tosyl ligand was found to occupy the apical position with I−OTs bond length of above 2.6 Å.…”

“…developed second‐generation chiral triazole‐substituted iodoarene‐precatalysts, also known as N ‐heterocycle‐substituted iodoarenes (NHIAs) [124–126] . While the first‐generation precatalyst 99 (Figure 13) successfully catalyzed Kita lactonization with ee s up to 86%, the second‐generation precatalysts developed by Nachtsheim, which contain an ortho ‐substituent, have been shown to be applicable to a number of asymmetric transformations like dearomatization of phenols, intramolecular oxygenation of ketones, tosyloxylation of ketones, oxidative rearrangement of allylic alcohols, and Kita lactonization [125] . The catalysis, in general, leads to the formation of desired products in very good yields and excellent enantioselectivities when compared to the results previously reported [127–133] with λ 3 ‐iodanes.…”

“…On the other hand, the structure 104c was found to be the most stable among 104a – d , where a dihedral angle of 93.86° was found. A high dihedral angle should facilitate the hypervalent twist, and the tosyl group with its good leaving group attributes can permit facile ligand exchange to render iodane reactive [125] …”