Aldehydes Meyers synthesis

Groups other than a carbonyl can stabilize a carbanion. Meyers described the preparation of a-lithio derivatives of dihydro-1,3-oxazines (282) and 2-oxazolines (284) and their use in alkylation and condensation reactions via a-lithio derivatives such as (283). Meyers treated the commercially available 285 with n-butyl-lithium to form the a-lithio derivative (286), stabilized by chelation with the nitrogen. When iodomethane was added, a carbanion displacement reaction occurred to give 287.The imine unit in 287 was reduced with borohydride (sec. 4.4.A) to give amine 288, and hydrolysis produced the aldehyde (in this case propanal). 

When 286 was treated with benzophenone, the initial condensation product, after hydrolysis, was the alcohol (289). Reduction of the imine moiety provided 290 and hydrolysis led to conversion of the oxazolidine to an aldehyde in 291. but this eliminated water under the hydrolysis conditions to give the conjugated aldehyde (292).-phis sequence is known as the Meyers aldehyde synthesis.Table shows 

Meyers and others showed that 2-oxazolines such as 295 are useful carbanionic synthons when they are converted to their a-lithio derivative. Reaction of 295 with ra-butyllithium, for example, gave 296. Addition of benzyl bromide gave the alkylated product 297, and heating that product in ethanolic sulfuric acid gave an 84% yield of the ethyl ester, ethyl 3-phenylpropanoate (298). Ketones react in a similar manner and the product is usually a conjugated acid derivative. 

These reactions are not limited to the simple oxazine and oxazolines described above. They are readily prepared from aldehydes and amino alcohols. Meyers used this methodology to prepare chiral precursors for use in asymmetric synthesis. When keto-acid 299 was treated with valinol (300), chiral bicyclic lactam 301 was 

It is clear that the Meyers aldehyde synthesis provides a facile route not only to a variety of aldehydes but also to esters, acids, and chiral derivatives. The disconnections available by this methodology include 

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The dihydro-1,3-oxazine route has been extensively investigated by Meyers. Controlled reduction to the tetrahydro derivative (53), followed by hydrolysis, gave good yields of the corresponding aldehyde or deuteriated aldehyde, R—CDO (Scheme 22). ° Further development of this concept has subsequently given rise to convenient routes to acyclic, a,3-unsaturated, ° alicyclic, y-hydroxy and y-oxo aldehydes. Full synthetic details of these and other variants of the Meyers aldehyde synthesis have been published. ... 

Meyers aldehyde synthesis. Synthesis of aldehydes R-CH2CHO from alkylhalides R-X and 2-lithiomethyl-tetrahydro-3-oxazine. 

Shown here is the mechanism of the Meyers aldehyde synthesis, including the formation of 5,6-dihydro-1,3-oxazine. 

Other references related to the Meyers aldehyde synthesis are cited in the literature. ... 

Meyer synthesis sintesis de Meyer Meyer aldehyde synthesis... 

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