Darzens reaction benzaldehyde

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good... 

In a separate report, the Darzens reaction was recently used by Barluenga, Concellon, and coworkers for the preparation of enantiopure a"-amino a,P-epoxy ketones. Accordingly, the Z enolate of a"-amino a-bromo ketone 41 was generated with KHMDS at -100°C. Benzaldehyde was added, and trans epoxyketone 42 was isolated in 87% yield and >95% de. ... 

The Darzens reaction can also proceed in the presence of a chiral catalyst. When chloroacetophenone and benzaldehyde are subjected to asymmetric Darzens reaction, product 89 with 64% ee is obtained if chiral crown ether 88 is used as a phase transfer catalyst (Scheme 8-30).69... 

It is prepared by treating ethyl cinnamate with peracetic acid [212] or by condensation of benzaldehyde with ethyl chloroacetate (in the above Darzens reaction, R = H). The glycidate is used as a long-lasting fragrance material for creating harmonic, fruity notes in household and fine fragrances. 

A somewhat more successful approach to asymmetric Darzens reactions has been observed in the reaction of a-halosulfones with aldehydes under phase-transfer conditions <07T8099>. The reaction of an a-chlorosulfone with benzaldehyde in the presence of quinine derived phase-transfer catalyst 11, provides the epoxide in excellent yield with very good enantioselectivity. The use of RbOH as the base was crucial to both yield and enantioselectivity. 

Similarly, the a-monochlorinated and a-monobrominated dimethyl 2-oxoalkylphosphonates are prepared in satisfactory yields (50%) by reaction of the sodium enolate of dimethyl 2-oxoalkyl-phosphonates with NCS or NBS in DME at room temperature- "- - or with bromine in Et20 (53-71%) or THE (60%) Synthesis of diethyl l-chloro-2-oxopropylphosphonate has also been reported through reduction of the 1,1-dichloro derivatives with sodium sulfite.- lodination in the Y-position of P-ketophosphonate 1,3-dianions prepared with KiCO, in MeOH has been reported. These dianions react with benzaldehyde in a Homer-Wadsworth-Emmons-Darzens reaction sequence to produce the a,P-unsaturated a, P -epoxyketones in 60-79% yields (Scheme 7.101).s ... 

Aldehydes can also be converted to enantioenriched chiral epoxides through the Darzens reaction. Thus, haloimides (e.g., 47) react with benzaldehyde in the presence of a novel phase transfer catalyst 45 derived from BINOL to give 1,2-disubstituted epoxides in good yields with... 

A Darzens reaction has been used to generate /rons-epoxides <05SL842>. Reaction of electron deficient p-substituted benzylammonium chlorides with benzaldehyde provides the trans-epoxide 46 in excellent to moderate yield as a 99 1 mixture of trans. cis epoxides. 

Chiral 2-substituted benzaldehyde chromium tricarbonyl complexes have been reacted with chloroacetophenone in the presence of KO-fert-Bu [544], After decomplexation, the E-epoxyketone is obtained with a high selectivity (Figure 6.88). This Darzens reaction with ClCF COO-tert-Bu is poorly stereoselective. Condensation of the same aldehydes with methyl aaylate or acrylonitrile in the presence of DABCO, followed by decomplexation, also leads highly selectively to P-hydroxyesters or -nitriles 6.105 (Y = COOMe or CN) [547] (Figure 6.88). An anti aldol product is also obtained with a high selectivity from a chromium complex and the titanium enolate of PhCF OCF COS-tert-Bu at -78°C [1281, 1282], Chiral aminals of a-ketoaldehydes react with lithium or sodium enolates of ethyl acetate. After treatment with acid, compounds 6.106 are obtained with a high enantiomeric excess (Figure 6.88). 

A Darzens-type condensation has been employed in the synthesis of (46) by the reaction of 9-chlorofluorene anion (45) with PhCHO.A two-phase system was used to prepare (f)-(47 R = H, Cl, or NO2) almost exclusively, via a Darzens reaction of the substituted benzaldehyde with PhCOCH2Br in the presence of a quaternary ammonium salt as catalyst. ... 

An analogous trend is observed in the Darzens reaction between acetaldehyde or benzaldehyde and a-chlorophenylacetonitrile. 

Stereochemical control of Darzen s reaction of a-chlorophenylacetonitrile with benzaldehyde by phase-transfer catalysts... 

Asymmetric induction using catalytic amounts of quininium or A-methyl-ephedrinium salts for the Darzen s reaction of aldehydes and ketones with phenacyl halides and chloromethylsulphones produces oxiranes of low optical purity [3, 24, 25]. The chiral catalyst appears to have little more effect than non-chiral catalysts (Section 12.1). Similarly, the catalysed reaction of sodium cyanide with a-bromo-ketones produces epoxynitriles of only low optical purity [3]. The claimed 67% ee for the phenyloxirane derived from the reaction of benzaldehyde with trimethylsul-phonium iodide under basic conditions [26] in the presence of A,A-dimethyle-phedrinium chloride was later retracted [27] the product was contaminated with the 2-methyl-3-phenyloxirane from the degradation of the catalyst. 

Later Takahashi et al.19 have reported an alternative synthesis of the cyanooxirane (40a,b) by carrying out the reaction between decyl bromide and potassium cyanide in the presence of quaternary ammonium catalysts. Compounds prepared by this method are similar to those obtained by the Darzens condensation with benzaldehyde in a two-phase system.78... 

The condensation of l-chloro-3-diazopiopanone (57) with aldehydes provides epoxy diazo ketones (equation 18). Treatment of a methanolic solution of (57) and benzaldehyde, in a stoichiometric ratio, with aqueous sodium hydroxide furnishes l-diazo-3,4-epoxy-4-phenyl-2-butanone (59a) in 69% yield the rrans-epoxide is obtained stereoselectively, analogous to the Darzens condensation of benzaldehyde and chloroacetone. The reaction is reported to proceed to give also the diazo ketones (59b-59e), and the epoxides obtained are exclusively of the trans configuration. ... 

B.vi. Tbe Darzens Glycidic Ester Condensation. When an a-halo ester is treated with base and the resulting enolate anion condensed with a carbonyl derivative, the product is an alkoxide. This nucleophilic species can displace the halogen intramolecularly to produce an epoxide, which forms the basis of a classical reaction known as the Darzens glycidic ester condensation. 13S Reaction of ethyl a-chloroacetate and sodium ethoxide, in the presence of benzaldehyde. generated the usual alkoxide (221). Intramolecular displacement... 

Specific situation of carbanions located at the interface can influence the steric course of the Darzens condensation. Thus the ratio of cis-trans isomers of 2,3-diphenylglycidonitrile produced in the reaction of phenylchloroacetonitrile with benzaldehyde in aqueous NaOH differs considerably with and without catalyst. 

Mamedov VA, Nuretdinov lA (1992) Reaction of methyl dichloroacetate with substituted benzaldehydes under the conditions of the Darzens condensation. Bull Rus Acad Sci Div Chem Sci 41(9) 1690-1692. doi 10.1007/BF00863594... 

---