Iron Catalyzed Highly Enantioselective Epoxidation of Cyclic Aliphatic Enones with Aqueous H₂O₂

Abstract

An iron complex with a C 1 -symmetric tetradentate N-based ligand catalyze the asymmetric epoxidation of cyclic enones and cyclohexene ketones with aqueous hydrogen peroxide, providing the corresponding epoxides in good to excellent yields and enantioselectivities (up to 99 % yield, and 95 % ee), under mild conditions and in short reaction times. Evidence is provided that reactions involve an electrophilic oxidant, and this element is employed in performing site selective epoxidation of enones containing two alkene sites.Introduction. Asymmetric epoxidation is a valuable reaction because chiral epoxides are versatile building blocks in synthetic organic chemistry. 1-4 Catalytic epoxidation methodologies based on iron complexes and peroxides (especially H 2 O 2 ), which can be considered as biologically inspired, are interesting because of the availability and low environmental impact of these reagents. [5][6][7][8][9][10][11][12][13][14][15]16 Despite appealing, the approach is challenging because it requires the design of iron coordination complexes that can activate the O-O bond of peroxides to create selective metal based oxidants, and avoid the often facile production of hydroxyl radicals via the Fenton reaction. 10,11,17,18 Recent reports have disclosed successful examples where asymmetric epoxidation is accomplished, in some cases producing high levels of stereoselectivity ( Figure 1). [19][20][21][22][23][24][25][26][27] Highly enantioselective epoxidation of difficult substrates such as ,-disubstituted aromatic enones and -alkyl styrenes, not accessible by other methods, have also been described. 23,24 However, a major limitation still resides at the fact that iron catalyzed asymmetric epoxidations have been limited in scope to olefins conjugated to aromatic rings, [19][20][21][22]23,[24][25][26][27][28][29][30][31][32][33][34][35] and remains to be accomplished for aliphatic substrates. Particularly interesting are cyclic aliphatic enones. Cyclic -epoxide enones are structures found in a number of natural products, 36 and are also valuable synthons that can be further elaborated into precious building blocks for organic synthesis. 37 However, their asymmetric epoxidation is notoriously difficult. Modest to good enantioselectivities have been obtained with chiral hydroperoxides, 38,39 poly(aminoacids) catalysts, 40 ammonium salt catalysts, [41][42][43] and metal based catalysts 21,22,44,45 , but excellent enantioselectivities have only been described by List and co-workers using cinchona alkaloid derived organocatalysts and hydrogen peroxide as oxidant. The main drawbacks of this system are the requirement of relatively high catalyst loadings (up to 10 %) and long reaction times (from 24 to 168 h). In addition,  and ' substituted enones are not valid substrates for the system. Highly enantioselective epoxidations that could improve these aspects will

Biologically Inspired C−H and C=C Oxidations with Hydrogen Peroxide Catalyzed by Iron Coordination Complexes

“…Very recently, Cussó et al. have explored C 1 ‐symmetric iron complexes containing a pdp backbone and two different heterocyclic arms . The most effective catalyst possesses a β‐TIPS‐substituted pyridine and a benzimidazole on the second arm (see ( S,S’ )‐[Fe(OTf) 2 ( Bz,TIPS pdp)] in Figure ).…”

“… Orthogonal regioselectivity in the asymmetric epoxidation of a dienone catalyzed by ( S,S’ )‐[Fe(OTf) 2 ( Bz,TIPS pdp)] and nucleophilic H 2 O 2 …”

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

“…The synthetic versatility of epoxides has established them as useful precursors to obtain a variety of polyfunctional derivatives or rearranged compounds 41, 42, 43, 44, 45, 46, 47. Cyclic α‐epoxide enones are found in a number of natural products, but asymmetric epoxidation of their precursors is notoriously difficult 48. The synthesis of β‐epoxy steroids has been achieved by using different chemical oxidants, such as chromyl diacetate, potassium permanganate salts, chiral ketones combined with oxone, and transition metal complexes in the presence of molecular oxygen 49.…”

Asymmetric Epoxidation of α,β‐Unsaturated Ketones Catalyzed by Chiral Iron Complexes of (R,R)‐3,4‐Diaminopyrrolidine Derived N4‐Ligands with Camphorsulfonyl Sidearms

“…Recently, Costas et al reported an iron complex with a C 1 ‐symmetric tetradentate ligand with a bulky pyridine and a benzimidazole moieties, which catalyzed the epoxidation of non‐aromatic substrates with aqueous H 2 O 2 , providing the epoxides in high yields and excellent enantioselectivities (up to 95% ee) . The experimental results also proved that the catalytic activity and stereoselectivity of an iron catalyst can be improved by enhancing the electron‐donating capacity and steric encumbrance of a ligand.…”