Ketones to imines

Figure 8.4 Transformations of aldehydes and ketones to imines, oximes, and enamines.

Additionally, transformation of carboxylic acids to esters and amides are illustrated in Figure 8.2. The related conversions of esters to acids and amides are shown in Figure 8.3. Finally, transformations of aldehydes and ketones to imines, oximes, and enamines are summarized in Figure 8.4. 

When ketone 419 and an ammonia saturated solution of methyl propiolate in methanol were heated in a Parr reactor, 2-pyridone 424 was obtained254. Presumably, the reaction course involves initial condensation of ammonia with the ketone to imine 420, which reacts via its enamine tautomer 421 in a Michael fashion with the methyl... 

Asymmetric Mannich-type reactions provide useful routes for the synthesis of enantiomerically enriched P-amino ketones or esters [48a, 48b]. For the most part, these methods involve the use of chirally modified enolates or imines. Only a handful of examples has been reported on the reaction of imines with enolates of carboxylic acid derivatives or silyl ketene acetals in the presence of a stoichiometric amount of a chiral controller [49a, 49b, 49c]. Reports describing the use of a substoichiometric amount of the chiral agent are even more scarce. This section contains some of the most recent advances in the field of catalytic enantioselective additions of lithium enolates and silyl enol ethers of esters and ketones to imines. 

W. Notz, S.-I. Watanabe, N. S. Chowdari, G. Zhong, J. M. Betancort, F. Tanaka, C. F. Barbas, Adv. Synth. Catal. 2004, 346, 1131-1140. The scope of the direct prohne-catalyzed asymmetric addition of ketones to imines. 

Primary amines undergo condensation reactions with aldehydes and ketones to imines secondary amines condense to enamines. 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Various methods have been employed to overcome this difficulty. For example, a method used by Chemical Abstracts involves naming the dihydro derivative of the heterocyclic ketone (or imine or exocyclic alkene) form, and adding the words mesoionic didehydro derivative (example 131). A similar approach, favoured by Ollis (76AHQ19)1), involves naming the corresponding cation hydroxide, with the prefix anhydro (indicating removal of the elements of water) (example 132). 

CLOKE - WILSON Cyclopropylkelone Rearrangement Rearrangement o( cyclopropyl ketones or imines to dihydnofurans or dihydropyrroles, thermally, photochemically, or by Lewis adds... 

Ketones and imines with adjacent perfluoroalkyl moieties show sharply reduced abilities to interact with electrophiles. Hexafluoroacetone is not protonated even in superacidic media... 

Imines also react with , -unsaturated aldehydes or ketones (219-221). 3,4-Dihydroisoquinoline reacts, for example, with methyl vinyl ketone to give cyclic ketone 146 (222,223). 

Primary amines, RNH2, add to aldehydes and ketones to yield imines, R2C=NR. Secondary amines, R2NH, add similarly to yield enamines, R2N—CR=CR2 (ene + amine = unsaturated amine). 

Reaction of an aldehyde or ketone with a secondary amine, R2NH, rather than a primary amine yields an enamine. The process is identical to imine formation up to the iminium ion stage, but at this point there is no proton on nitrogen that can be lost to form a neutral imine product. Instead, a proton is lost from the neighboring carbon (the a carbon), yielding an enamine (Figure 19.10). 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

Active Figure 24.4 MECHANISM Mechanism of reductive amination of a ketone to yield an amine. Details of the imine-forming step were shown in Figure 19.8 on page 711. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Finally, chromium imine carbenes underwent photoreaction with imines to give azadienes (metathesis) (Eq. 36), with azobenzene to give both metathesis and cycloaddition products (Eq. 37), and with ketones to give oxazolines... 

Compounds containing carbon-nitrogen double bonds can be hydrolyzed to the corresponding aldehydes or ketones. For imines (W = R or H) the hydrolysis is easy and can be carried out with water. When W = H, the imine is seldom stable enough for isolation, and hydrolysis usually occurs in situ, without isolation. The hydrolysis of Schiff bases (W = Ar) is more difficult and requires acid or basic catalysis. Oximes (W = OH), arylhydrazones (W = NHAr), and, most easily, semicarbazones (W = NHCONH2) can also be hydrolyzed. Often a reactive aldehyde (e.g., formaldehyde) is added to combine with the liberated amine. 

This chapter discusses the development of scaleable and robust manufacturing processes for rhodium and rathenium containing precatalysts that are used for the asymmetric hydrogenation of a diverse range of olefins, ketones and imines. The application of these precatalysts to the preparation of a variety of pharmacentical intermediates, many of which have been operated on commercial scale, is also discussed. 

Addition of enols, enolates, or enolate equivalents to imines or iminium ions provides an important route to (3-amino ketones. 

In addition to undergoing cycloaddition reactions with alkenes and al-kynes, silenes readily undergo cycloaddition reactions with heteroatom multiple bonds such as C=0 and C=N, most commonly when the trapping reagent for the silene is either an aldehyde, ketone, or imine. In many... 

Conversion of a ketone to a highly substituted imine interestingly leads to a compound which shows analgesic activity, anidoxime (197). Phenyl 2-di-ethylaminoethyl ketone is converted to its oxime (196) in the usual way, and this is converted to... 

Among the most active catalysts for the asymmetric transfer hydrogenation of prochiral ketones and imines to chiral alcohols and amines are arene-ruthenium(II) amino-alcohol (or primary/ secondary 1,2-diamine)-based systems, with an inorganic base as co-catalyst, developed by Noyori139-141 and further explored by others (Scheme 27).142-145... 

While it is beyond the scope of this chapter to cover the asymmetric hydrosilylation of ketones and imines in any detail, a number of the more catalytically active ML combinations will be mentioned here. A full review of the area has recently appeared.138 Asymmetric hydrosilylation of carbonyl groups is usually performed with rhodium or titanium catalysts bearing chelating N- or P-based ligands. Representative results for some of the most active Rh/L combinations (Scheme 32) for addition of Si H to acetophenone are given in Table 11. 

As an extension of the asymmetric hydrogenation of prochiral ketones to enantiomerically enriched alcohols, the reduction of imines has been a topic of interest in obtaining chiral amines of high enantiomeric purity. Several entries to enantiomerically enriched amines based on the approaches outlined above are available. These asymmetric hydrogenations have proved to be more difficult than those for prochiral ketones, but nevertheless show good promise. 

As outlined in Section II,E, ketone and imine groups are readily hydrogenated via a hydrosilylation-hydrolysis procedure. Use of chiral catalysts with prochiral substrates, for example, R,R2C=0 or R,R2C=N— leads to asymmetric hydrosilylation (284, 285 Chapter 9 in this volume) and hence optically active alcohols [cf. Eq. (41)]. 

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