Epoxidation of benzaldehyde with

Scheme 10.37 Sulfide-catalysed epoxidation of benzaldehyde with BnBr.

Reduction of the amount of catalyst was also investigated by the Metzner group in the epoxidation of benzaldehyde with methylallyl iodide [208], Although use of 10 mol% 215 resulted in comparable yields, diastereomeric ratio, and enantiomeric excess, the reaction time was very long - one month. Addition of tetra-n-butyl ammonium iodide was not beneficial in this reaction, probably because of poor compatibility of the produced epoxide with this additive [208]. 

Recently, several sulfides with a bicyclo[3.2.1] framework have been developed for the ylide epoxidation reaction. In 2008, Metzner and coworkers prepared several bridged sulfides starting from (R)-carvone, which were then evaluated in the epoxidation of benzaldehyde with benzyl bromide (Scheme 20.8). Sulfide 12 was found to be the most enantioselective, delivering the desired trans epoxide in 54% yield and 84% ee in 4 days. Sulfide 15, which was prepared from 12 by reacting with PhLi followed by dehydration, is much more reactive than 12, providing 80% yield in one day but the enantioselectivity was lower (55% ee) [19]. 

Treatment of benzaldehydes with ethyl diazoacetate and a catalytic quantity of the iron Lewis acid [ -CpFe(CO)2(THF)]+BF4 yields the expected homologated ketone (80). However, the major product in most cases is the aryl-shifted structure (81a), predominantly as its enol tautomer, 3-hydroxy-2-arylacrylic acid (81b). This novel reaction occurs via a 1,2-aryl shift. Although the mechanism has not been fully characterized, there is evidence for loss of THF to give a vacancy for the aldehyde to bind to the iron, followed by diazoacetate attachment. The product balance is then determined by the ratio of 1,2-aryl to -hydride shift, with the former favoured by electron-donating substituents on the aryl ring. An alternative mechanism involving epoxide intermediates was ruled out by a control experiment. 

CsX is useful for the simple Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate even a simple NaY is sufficiently basic to form carbamates starting from primary aromatic amines and dialkyl carbonates (35, 36). At contrast CsjO-MCM-41 can also be used for the addition of C02 to epoxides, or for Michael addition of one or two molecules of diethyl malonate on neopentylglycol diacrylate (37, 38) ... 

The few published attempts at the asymmetric epoxidation of carbonyl compounds with chiral sulfur ylides have been reviewed. Thus far, such processes have not been very useful synthetically. For example, reaction of benzaldehyde with an optically pure sulfoximine ylide only afforded an qioxide in 20% enantiomeric excess. More recently, chiral sulfur methylides have provided tra/i -stilbene oxides in up to 83% ee An example of optical induction observed in reactions t ng place with a chiral phase transfer reagent was reported, but later disputed. ... 

Various magnesium oxide crystals [commercial MgO, CM-MgO (SSA 30 m /g), conventionally prepared MgO, NA-MgO (SSA 250 m /g), aerogel prepared MgO, NAP-MgO (SSA 590m /g)] were initially evaluated in the CSC and AE reactions separately in order to understand the relationship between structure and reactivity. All these MgO samples catalyzed both CSC of benzaldehyde with acetophenone to form chalcone quantitatively and selectively, and subsequent AE using (- -)-diethyl tartrate (DET) as a chiral auxiliary to obtain a chiral epoxy ketone in good yield and impressive ee. The nanocrystalline MgO (NAP-MgO) was found to be more active than the NA-MgO and CM-MgO in the condensation and epoxidation reactions (Figure 5.6). 

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

The iron cationic complex [Cp(CO)2Fe(THF)]BF4 catalyzed epoxidation reaction of benzaldehyde with phenyldiazomethane [88]. a-Benzaldehyde iron complex as... 

Fumkawa and coworkers realized the first enantioselective substoichiometric epoxidation reaction of aldehydes via the sulfide alkylation/deprotonation route, based on their one-pot procedure for the synthesis of oxiranes using sulfides directly rather than the preformed sulfonium salts [6]. In the presence of 50mol% sulfide 1, which was prepared in three steps starting from (-l-)-camphorsulfonic acid, a 50% yield and 47% ee were obtained in the reaction of benzaldehyde with benzyl bromide under solid-liquid two-phase conditions (solid KOH/CH3CN). A catalyst turnover (TON = 2.3) was also observed when 10mol% catalyst was used in the reaction of 4-chlorobenzaldehyde (Scheme 20.3). The 0-methylated derivative of sulfide 1 gave the trows epoxides with an opposite configuration. 

The authors later successfully extended (2R,5R)-2,5-dimethylthiolane to the allylidene transfer to aldehydes. The epoxidation reaction of benzaldehyde with methallyl iodide gave the desired vinyl oxirane in 60% yield, 50 1 dr, and 86% ee. The addition of n-Bu4Nl failed to improve the yields to an acceptable level, probably due to the poor compatibility of this additive with the oxirane products [23]. 

A type of axial chiral sulfide based on the binaphthyl scaffold was reported by Uemura and coworkers in 2002. In the reaction of benzaldehyde with benzyl bromide in dichloromethane with the addition of n-Bu4NI, a 44% yield and 50% ee were obtained in 24h at a 5mol% catalyst loading. The 3,3 -phenyl derivative 9b was much less reactive and gave only a trace amount of the epoxide product [16]. 

In catalytic epoxidation reactions an alternative to the ylide generation method via alkylation/deprotonation is the transition metal-mediated carbene transfer from diazo compounds to sulfide catalysts. In 1994, Aggarwal and coworkers employed this method in the enantioselective catalytic epoxidation of aldehydes [25]. Using 20mol% of non-racemic sulfide 17 and lmol% of Rh2(OAc)4 together with the slow addition of PhCHN2, a 58% yield and 11% ee were obtained in the epoxidation of benzaldehyde (Scheme 20.10). The enantioselectivity was similar to the results obtained by Breau and Durst using preformed sulfonium salts [26]. 

As stoich. [Ru(0)(bpy)(tmtacn)]VCH3CN it functioned as a competent (sic) epoxidant for alkenes, though the products were often contaminated with by-products (e.g. fran -stilbene gave fran -stilbene oxide and benzaldehyde cw-stilbene gave cis- and trans- epoxides). Kinetics of the epoxidation of norbomene and styrene were reported, with activation parameters measured and discussed [682]. Kinetics of its non-stereospecific, stoicheiometric epoxidation of aromatic alkenes in CH3CN were studied, and the rates compared with those of oxidations effected by other Ru(IV) 0x0 complexes with N-donors, e. g. [Ru(0)(tmeda)(tpy)] ", trans-[Ru(0)(Cl3bpy)(tpy)] " and [Ru(0)Cl(bpy)(ppz )] + [676]. 

Alkylidene derivatives of phthalic thioanhydride are formed as shown in Scheme 160. Reaction of phthalic thioanhydride with hot triethyl phosphite produces trafts-S -bithioph-thalide (457), probably via the carbene and phosphorane (Scheme 161) (72AHC(14)331>. Support for this mechanism stems from the fact that brief treatment of phthalic thioanhydride with triethyl phosphite in the presence of phthalic anhydride gives (458) in the presence of benzaldehyde the same reaction leads to the benzylidene derivative (456). An alternative mechanism has also been suggested, in which the penultimate step is the formation of an epoxide, which is deoxygenated to yield the product (72AHC(14)331>. 

To a solution of benzaldehyde (1.06g. lOmmol) in CH2CI2 (10ml) were added trimethylsulfonium methyl sulfate (2.17 g, 11.5 mmol) and 50% aqueous NaOH (5 ml). The reaction mixture was magnetically stirred at room temperature for 2.5 h. Water (20-30 ml) was added and the organic phase was decanted. The aqueous phase was extracted twice with ether (2 X 20ml). The combined organic solution was washed twice with water and dried (CaCl2). The solvents were evaporated under vacuum (rotatory evaporator, cold bath) and the epoxide distilled (l-2g, 80%), b.p. 82°C/38 torr. 

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