A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins

Abstract

A fructose-derived diacetate ketone has been shown to be an effective catalyst for asymmetric epoxidation. High ee's have been obtained for a variety of trans-and trisubstituted olefins including electron-deficient α,β-unsaturated esters as well as certain cis-olefins.Chiral ketones of various structures have been extensively investigated for asymmetric epoxidation of olefins in a number of laboratories. 1 In our studies, we have found that fructosederived ketone 1 provides high ee's for a wide variety of trans-and trisubstituted olefins, 2 and oxazolidinone ketone 2 can give high ee's for olefins which had not been effective with ketone 1, including various cis-olefins, 3a,c,d,e,g,k,l styrenes, 3b,c,d,f and certain trisubstituted 3h,j and tetrasubstituted olefins. 3i,j In our efforts to expand the substrate scope, we have reported that ketone 3a is an effective epoxidation catalyst for a variety of electron-deficient α,β-unsaturated esters. 4 Replacing the fused ketal of 1 with more electron-withdrawing diacetates significantly enhances the ketone's reactivity and possibly reduces the Baeyer-Villiger decomposition. Herein we wish to report our detailed studies on epoxidations with ketone 3a and its related analogues.Email: yian@lamar.colostate.edu. Ketone 3a can be synthesized from ketone 1 in two steps by selective deketalization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) 5 and subsequent acetylation with Ac 2 O and catalytic amount (2 mol%) of DMAP (Scheme 1). 4 Ketone 3a is highly electrophilic and can easily form a hydrate with water. 6 With this method, ketone 3a can be obtained largely in ketone form by avoiding moisture. The β-acetate of ketone 3a is prone to elimination to form an enone. To minimize this elimination, it is crucial to use only a small amount of DMAP (ca. 2 mol%) and to carefully control the reaction time in the acetylation step. Nevertheless, it was found that the resulting enone was barely active and had little impact on the asymmetric epoxidation. Alternatively, ketone 3a can be readily prepared in hydrate form from ketone 1 by one pot deketalization and acetylation with ZnCl 2 , AcOH, and Ac 2 O in water (Scheme 2). 7,8,9 However, if ketone 3a is desired, it can be obtained from 3a·H 2 O by simply dissolving 3a·H 2 O in solvents such as EtOAc and stirring with Na 2 SO 4 overnight at rt, followed by filtration and concentration or by passing 3a·H 2 O through a short column of SiO 2 . In CDCl 3 , the hydrate gradually converted into the ketone as judged by 1 H NMR (25% ketone at 10 min, 50% ketone at 30 min, 67% ketone at 1 h, 90% ketone at 2 h, 100% ketone at 11 h). In CD 3 CN-D 2 O (1.5:1, v/v), ca. 21% of the ketone was formed from the hydrate at 1 h (ca. 22% at 7 h). When the ketone was subjected to the same solvent mixture, ca. 26% of the ketone remained at 1 h (ca. 25% at 7 h). It appears that a similar amount of the ketone was present at around 1 h regardless of whether the ketone or its hydrate was used. Similar conversions and ee's were also obtained for the e...

Heterogenisation of ketonecatalysts within mesoporous supports for asymmetric epoxidation

“…12 Elemental analysis of both silicas 9a and 10a showed clear incorporation of the thiol, and from nitrogen analysis of 10a the loading of the catalyst was estimated to be 0.20 mmol g 21 (entries 3 and 4, Table 1). IR spectroscopy confirmed the presence of the ketone (v CO 1770 cm 21 ).…”

“…Concentration in vacuo gave a yellow oil which was purified by silica gel column chromatography eluting with 2 to 3% MeOH : CH 2 Cl 2 to give the title compound as a clear oil (383 mg, 1.10 mmol, 100%). IR n max (neat)/cm 21 .9, 138.3, 132.9, 129.2, 114.7, 109.3, 96.3, 77.4, 73.6, 72.1, 59.5, 50.5, 35.8, 34.4, 28.1, 26.1…”

Organokatalytische asymmetrische Epoxidierungen – Reaktionen, Mechanismen und Anwendungen

“…Diese Untersuchungen zeigten, dass die relative Hydrophobie der Alkensubstituenten und/oder der allylischen Sauerstofffunktionalität die Stereodifferenzierung der prochiralen Seiten des Substrats ermçglichen kçnnte. [44] Weitere Anstrengungen wurden unternommen, um die sterischen und elektronischen Eigenschaften bekannter Katalysatoren auf Basis chiraler Ketone zu kombinieren. [43] Bei einigen Substraten wirkte das Fluoratom durch elektronische Wechselwirkungen mit dem Katalysator als dirigierende Gruppe, in anderen Fällen war es jedoch nachteilig für die Selektivität der Reaktion.…”

“…Bei elektronenarmen Alkenen wie a,b-ungesättigten Estern erwies sich das Keton 44 als wirksamer als 42 und 43. [44] Weitere Anstrengungen wurden unternommen, um die sterischen und elektronischen Eigenschaften bekannter Katalysatoren auf Basis chiraler Ketone zu kombinieren. Um den Substratbereich zu erweitern wurden die Lactamketone 45, die eine Morpholingruppe haben, vorgestellt (Schema 12).…”

d-Fructose-derived β-amino alcohol catalyzed direct asymmetric aldol reaction in the presence of p-nitrophenol

“…Peddinti and co-workers 9 rst reported the glucosamine-based primary amine used independently as bifunctional organocatalyst in asymmetric synthesis. 16 As it is cheaper and has more structural exibility than glucosamine, D-fructose was selected as the chiral pool in our studies, with the aim of widening its use in asymmetric transformations. 1) bearing a free hydroxyl group vicinal to primary amine functionality provided the best results in direct asymmetric aldol reaction through hydrogen bonding between the proton on the hydroxyl moiety and the carbonyl group of the aldehyde.…”