Darzens aldehyde synthesis

Barbier-Wieland degradation Boudroux-Chichibabin synthesis Bouveault aldehyde synthesis Darzens synthesis Friedel-Crafts Reaction Gatterman-Koch reaction Grignard reaction Reformatsky reaction Saytzeff reaction Ullmann coupling reaction Wiirtz coupling reaction Wiirtz-Fittig reaction... 

DAKIN Oxidation 84 DAKIN WEST Acylation 84 DANHEISER Annutation 85 DANISHEFSKY Sitytoxydenes 66 DARAPSKI Ammoacid synthesis 87 DARZENS - NENITZESCU Acylation 67 DARZENS Epoxide synthesis 88 DAVIDSON Oxazola synthase 89 OELEPINE Aldehyde oxidation 89 DAVIS Oxidumg reagent 90 Decker 127... 

Several name reactions are promoted by AICI3. For example, the Darzens-Nenitzescu reaction is simply the acylation of alkenes. The Ferrario reaction generates phenoxathiins from diphenyl ethers (eq 19) The rearrangement of acyloxy aromatic systems is known as the Fries rearrangement (eq 20). Aryl aldehydes are produced by the Gatterman aldehyde synthesis (eq 21). The initial step of the Haworth phenanthrene synthesis makes use of a Friedel-Crafts acylation. The acylation of phenolic cort tounds is called the Houben-Hoesch reaction (eq 22). The Leuckart amide s)oithesis generates aryl amides from isocyanates (eq 23). ... 

Of interest is a recent report of a rapid synthesis of efaroxin (51), a potent, selective O2 adrenoceptor antagonist, using Darzens Reaction. Accordingly, a-bromoester 48 was condensed with aldehyde 47. The glycidic ester (49) was then hydrogenated to reduce the more labile epoxide bond to give alcohol 50. Subsequent standard transformations subsequently lead to a completed 4-step synthesis of efaroxin. o... 

The aza-Darzens reaction is analogous to the Darzens synthesis of epoxides (see Section 1.2.3.2) but employs imines in the place of aldehydes (Scheme 1.27). 

An unexpected, one-step synthesis of a-chloro-P-lactones in 40-83% yield resulted when phenyl esters of a-chlorocarboxylic acids were treated under the conditions of the Darzens reaction with strong base in the presence of ketones or aldehydes <95AG(E)2028>. Previously, phenyl esters do not appear to have been used in this reaction. 

The use of quininium salts can add to the high stereoselectivity (65-80% ee) that can be achieved under phase-transfer catalytic conditions in the synthesis of oxiranes by the Darzens reaction (Section 12.1) from chloromethylsulphones and aromatic aldehydes [6],... 

A number of glycidates are important intermediates in the synthesis of fragrance materials. A few glycidates are fragrance materials in themselves. They are prepared either by epoxidation of the corresponding acrylates or by condensation of aldehydes or ketones with a-chloro substituted fatty acid esters (Darzens reaction). 

In the past, Darzens methodology was primarily used for the synthesis of aldehydes and ketones, as a homologation reaction without any consideration of stereocontrol in the epoxide formation. For this sequence, saponification of the a,P-epoxy ester followed by decarboxylation gives the substituted carbonyl compound ... 

By the Darzens reaction. -ionone afforded a C14 aldehyde which as the diethyl acetal underwent addition to ethyl vinyl ether in the presence of boron trifluoride etherate to yield a Cl6 acetal. After hydrolysis, loss of ethanol and formation of the diethyl acetal as before, reaction under acidic condiions with ethyl propenyl ether gave the unsaturated Cl9 aldehyde after hydrolysis and removal of ethanol. Reaction of two moles with ethyne dimagnesiuro bromide produced the C40 chain and dehydration of the diol, selective catalytic hydrogenation followed by isomerisation completed a remarkable technical synthesis of i-carotene. Further variations have involved the use of two moles of the C14 aldehyde and a Cl2 divinyl ether. An independent approach (ref.29) has utilised vitamin A (32) converted to a phosphonium salt, thence to the corresponding phosphoran, autoxidation of which afforded s-carotene ( scheme 16). 

Synthesis of glycidic esters. The Darzens reaction1 fails with compounds such as acetaldehyde which give only self-condensation products. Borch2 has described a new procedure which is generally applicable. The a-bromo ester anion (2) is smoothly generated by reaction with lithium bis(trimethylsilyl)amide in THF at —78°. Addition of the aldehyde or ketone at —78° followed by workup affords the corresponding... 

Later, Arai, and coworkers applied their PTC-mediated Darzens reaction conditions to the synthesis of optically active oc, 3-epoxysulfones [43], The reaction of the chloromethyl phenyl sulfone 102 with aromatic aldehydes under PTC conditions (101 (10mol%), KOH-toluene) at room temperature afforded the desired trans-epoxysulfones 103 in good yields and with moderate to good ee values (33-81%) (Scheme 8.35). On the other hand, aliphatic aldehydes gave the Darzens product as the racemates. The use of a Lewis acid additive (Sn(OTf)2) improved the selectivity, but only slightly (up to 32% ee). Under PTC conditions, chloromethylsulfone is transformed into the corresponding carbanion, which then reacts with the... 

The Darzens glycidic ester condensation involves the condensation of an aldehyde or ketone with an a-halo ester, in the presence of a base, to afford an a,3 epoxy ester (a glycidic ester ). The first synthesis of a glycidic ester was reported by Erlenmeyer in 1892 and is illustrative of the general reaction, as shown in equation (1). The reaction was subsequently developed and generalized by Darzens. Glycidic esters, in addition to undergoing transformations normally associated with epoxides, afford upon hydro-... 

Numerous other reactions of carbanions are efficiently executed in two-phase systems using concentrated aqueous NaOH and PT catalysts for deprotonation of the carbanion precursors. These conditions are particularly suitable for synthesis of oxiranes via condensation of aldehydes and ketones with carbanions of, e.g., ot-chloronitriles, sulfones, and esters of a-chlorocarboxylic acids, known as the Darzens reaction, or with sulfonium... 

The Cl 4-aldehyde 7 is also a key intermediate in the technical synthesis of vitamin A. It can be prepared from p-ionone f7J in a Darzens glycidic ester condensation by the reaction with ethyl chloroacetate (16) via 17 as intermediate. The chain elongation to the Ci9-aldehyde 72 was achieved by reaction with the acetylenic Cs-compound 18 (Scheme 4). 

The epoxy esters formed in the Darzens condensation have been used in the synthesis of ketones and aldehydes. The acids formed by saponification of the esters... 

Modified Darzens-Claisen reaction Aldehydes from ketones via glycidic acid tertAmiyX esters Synthesis with addition of 1 -atom... 

In addition to alkenes, imines are tremendously popular aziridine precursors via an aza-Darzens approach. For example, a stereoselective synthesis of C-sulfonylated aziridines was reported via an aza-Darzens approach employing bromomethyl phenyl sulfbne, NaHMDS, and a series of N-tert-butanesulfinyl imines (14MI969). Likewise as shown below, chiral tert-butane- and mesitylsulfinimines were subjected to an aza-Darzens reaction with substituted 2-bromoesters to provide a host of aziridines in good yield with excellent stereocontrol (14OL6920). In turn, these aziridines could be subsequently converted to chiral A/-H aziridines in a total of three steps starting with a wide range of commercially available aldehydes. 

When an aldehyde or a ketone is condensed with ethyl a-chloroacetate in the presence of sodium ethoxide, the product is an a,j8-epoxy ester called a glycidic ester. The synthesis is called the Darzens condensation. 

A diastereo- and enantioselective Michael addition combined with a Darzens condensation reaction can be used to form two products of interest in the field of medicinal and natural products chemistry [60]. Additionally, depending on the workup conditions, an optically active epoxycyclohexanone, 92, can be prepared through an Sf 2 reaction, or the ElcB reaction pathway to 91 can be accessed (Scheme 7.17). In the early stages of the proposed mechanism, a planar iminium ion is suggested between the 2-[bis(3,5-bistrifluoromethylphenyl) trimethylsilany-loxymethyljpyrrolidine 61 and the aldehyde moiety of compound 88, which is subsequently attacked by the P-ketoester 89. For the synthesis of the epoxide, a... 

Sodium alcohol (s. a. under Cu and Ni(CO)J Darzens-Claisen reaction Synthesis of ketones from aldehydes via glycidic acid esters... 

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