Enantioselective Nitrene Transfer to Sulfides Catalyzed by a Chiral Iron Complex

Abstract

Sulfimides are nitrogen analogues of sulfoxides. [1] In organic synthesis, they serve as useful intermediates [1,2] and have been applied as efficient ligands for metal catalysts. [3] Because of their unique biological properties, [1a, 4] sulfimides have also gained considerable attention in agricultural science and medicinal chemistry. As sulfoxides, sulfimides are chiral and have a stereogenic center at the sulfur atom if they originate from unsymmetrically substituted sulfides. Although sulfimides can be easily synthesized by various means, [1,5] their preparation in enantioenriched form is still challenging. The most prominent strategies involve the use of chiral auxiliaries [3a, 6] or reagents. [7] All of those, however, require stoichiometric amounts of chiral compounds that are usually prepared by multi-step syntheses.The field of catalytic asymmetric sulfimidation is scarcely explored, and only very few catalyst systems have been documented. For example, Uemura, Taylor and their coworkers disclosed the use of chiral copper(I)/bis(oxazoline) catalysts. [8] However, only sterically hindered aryl benzyl sulfides gave satisfying results. Subsequently, Katsuki and coworkers introduced chiral manganese(III)/salen [9] and ruthenium(II)/salen [10] (or salalen) [11] complexes as asymmetric sulfimidation catalysts. Excellent results were achieved, but the synthesis of salen ligands proved cumbersome.Inspired by the early work of Bach [5a,b] and encouraged by our findings that simple iron(II) and iron(III) compounds could effectively catalyze non-asymmetric sulfide imidations, [5h-j] we decided to focus our search on chiral iron complexes for asymmetric versions of such reactions. Herein, we report that iron(III)/PyBOX combinations are highly effective catalysts for the aforementioned transformations. Noteworthy, this is the first iron-catalyzed enantioselective sulfimidation reported to date, despite many other breakthroughs in asymmetric iron catalysis. [12,13] The asymmetric imidation of thioanisole (1 a) with N-(ptolylsulfonyl)imino phenyliodinane (PhI=NTs) in acetonitrile was selected as the benchmark reaction for our preliminary screening. Various catalysts formed in situ from chiral ligands and iron(III) acetylacetonate ([Fe(acac) 3 ], 3 a) were tested.

Enantioselective Imidation of Sulfides via Enzyme-Catalyzed Intermolecular Nitrogen-Atom Transfer

“…Indeed, the specific activities of the enzyme catalysts reported here compare favorably with enantioselective iron-based catalysts, which routinely require catalyst loadings of 10 mol %. 9b Furthermore, engineering the holoenzyme or reductase domain to favor one-electron transfers might improve the proportion of desired product relative to azide reduction, which could allow reaction with more challenging organic acceptor substrates.…”

“…8 Subsequent oxidation to form sulfoximines can be achieved with good chirality transfer, 9 and the resulting compounds are a promising source of novel derivatives of therapeutic small molecules. 10 Furthermore, sulfides substituted at the sulfur position with allyl groups can undergo a 2,3-sigmatropic rearrangement upon sulfimidation, resulting in formation of a new C–N bond.…”

Sulfur imidations: access to sulfimides and sulfoximines

“…Recently, a considerable improvement in the enantioselective synthesis of sulfimides and sulfoximines has been achieved by using a catalyst consisting of an iron(III) salt combined with a PyBOX ligand. 53,54 The investigation of enantioselective sulfimidations showed that 5-10 mol% of Fe(dmhdCl) 3 (dmhd = 4-chloro-2,6-dimethyl-3,5-heptanedionate) along with 5-10 mol% of (R,R)-Ph-PyBOX 82 and PhIQNTs as nitrene source was the View Article Online best combination providing sulfimides 83 in high yields and enantiomeric ratios of up to 96 : 4 for a broad substrate scope (Scheme 30, top). Noteworthy, the reactions proceeded smoothly in acetone (cheap, low toxicity) at low temperature, without exclusion of air and moisture.…”

Tunable regioselectivity in 1,3-butadiene polymerization by using 2,6-bis(dimethyl-2-oxazolin-2-yl)pyridine incorporated transition metal (Cr, Fe and Co) catalysts

“…2,6-bis(oxazolin-2-yl)pyridines are versatile ligands assisted in metal catalysts for various organic transformation due to their feasible syntheses and easy modification of the steric and electronic properties, in particular, adjusting enantioselectivity via introducing chiral center into appropriate place of ligand has led to tremendous efficient chiral catalysts for organic building [49][50][51][52]. Description of their catalysis behavior for polymerization, however, is conspiculously less, and reported examples are only limited in chromium [53], iron [54] and ruthenium catalysts [55].…”