Ketones cyclic imines, reactions with

Chiral oxazolidines 6, or mixtures with their corresponding imines 7, are obtained in quantitative yield from acid-catalyzed condensation of methyl ketones and ( + )- or ( )-2-amino-l-phcnylpropanol (norephedrine, 5) with azeotropic removal of water. Metalation of these chiral oxazolidines (or their imine mixtures) using lithium diisopropylamide generates lithioazaeno-lates which, upon treatment with tin(II) chloride, are converted to cyclic tin(II) azaenolates. After enantioselective reaction with a variety of aldehydes at 0°C and hydrolysis, ft-hydroxy ketones 8 are obtained in 58-86% op4. 

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

A Schiff base is the common name for the (usually acyclic) imine product of the reaction of a primary aryl amine with an aldehyde or ketone. These imines are stable if there is at least one aryl group on the imino nitrogen or on the imino carbon (54). A cyclidene is generically a cyclic, multidentate imine. 

The CCl4-HF-SbF5 system developed by Jouannetaud and co-workers and used in the selective fluorination of imines (see Section 5.10.1) can be applied in the oxygenation of ketones and carboxamides as well. The hydroxylation of ketones is selective [Eq. (5.229)], provided that a five- or six-membered cyclic carboxonium ion preventing fluorination is involved.534,659 Fluorination, however, may be a side reaction with product distributions depending on quenching conditions (aqueous Na2CC>3 or HF-pyridine). Similar features are characteristic of the transformation of carboxamides.659... 

Aza- Wittig reaction, cyclic imines. Treatment of the azido ketones 1 with triphenylphosphine at room temperature results in a cyclic imine (2) in good yield, formed by an intramolecular aza-Wittig reaction.2... 

As mentioned previously, the cyclization of phenethyl ketone oximes with [Bu4N]Re04 and CF3SO3H and the cyclic imine formation from 0-sulfonyl oximes both proceed by intramolecular S 2-type reaction on the nitrogen atom of the oximes (Scheme 33). ° In contrast, both of the E- and Z-isomers cyclized smoothly and only 8-hydroxyquinoline was obtained regioselectively without forming 6-hydroxy derivatives. These phenomena are not consistent with a nucleophilic substitution reaction, and the cyclization of 0-2,4-dinitrophenyloxime 80a seemed to proceed by another reaction pathway (Scheme 37). To check isomerization of the 0-2,4-dini-trophenyloxime 84, the Z-isomer was treated with NaH and m-cresol. The isomerization of (Z)-84 hardly occurred, but 4-phenylbutan-2-one azine (85) and 4-phenyl-2-butanone (86) were obtained in 27 and 11%... 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

Radical cyclization is not limited to reaction with a C=C unit (see 15-29 and 15-30), and reactions with both C=N and C=0 moieties are known. Reaction of MeON=CH(CH2)3CHO with Bu3SnH and AIBN, for example, led to trans-2-(methoxyamino)cyclopentanol in good yield.Conjugated ketones add to aldehyde via the p-carbon under radical conditions (2 equivalents of Bu3SnH and 0.1 equivalent of CuCl) to give a p-hydroxy ketone.Addition of radical to the C=N unit of R C=N SPh ° or R—C=N—led to cyclic imines. Radical addition to simple imines leads to aminocycloalkenes. Radical also add to the carbonyl unit of phenylthio esters to give cyclic ketones. 

Taylor and Raw recently designed a tethered imine-enamine cascade sequence that converts 1,2,4-triazenes into substituted pyridines. In the presence of molecular sieves, A-methylethylenediamine (147) underwent condensation with excess cyclic ketone 148 (n — 1-4) to give imine-enamine 150 (04CC508). The enamine portion of the molecule then participated in an inverse-demand Diels-Alder cycloaddition reaction with 149 to provide intermediate 151. Cycloreversion of 151 with loss of N2 then gave 152 in which the tertiary amino group underwent addition to the adjacent imine functionality to afford zwiterionic 153. Finally, an intramolecular Cope elimination produced 154 in 74-100% yield. Several other triazines were also shown to participate in this novel cascade (Scheme 27). 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

In some cases it is appropriate to use an imine instead of a carbonyl compound. Thus, benz-alaniline reacts with activated methylenes in the presence of carbocyclic acid anhydrides to give the corresponding Knoevenagel products (Scheme 21) Similarly, the enamine (170) reacts with cyanoacetic acid in ethyl acetate or dimethylformamide to afford the cyclohexylidene compound (171 Scheme 28). Acetals may be employed instead of the free ketones. An example is the reaction of fluorenone cyclic acetal (172) with malon initrile, which occurs in butanol without added catalyst to af-... 

Reactions of free ketones with imines are far more restricted than those with preformed iminium salts. Examples of ketone-imine condensations are included in several reviews - and are limited to the use of arylimines, mainly benzylideneaniline. Blatt and Gross have noted that the reproducibility of uncatalyzed additions of ketones to Schiff bases is poor but can be improved by the addition of small amounts of hydrochloric acid. The highest yields of 3-amino ketones are obtained using 10 mol % of concentrated hydrochloric acid and 95% ethanol as solvent, and by performing the reaction at room temperature. The reaction, however, is of limited applicability, as it is restricted to methyl ketones and cycloalkanones. Deamination leading to unsaturated ketones is a major side reaction. In addition to hydrochloric acid, boron trifluoride etherate has been used as a catalyst in reactions of aromatic imines with methyl ketones, cyclic ketones and an epoxy ketone. ... 

Under strictly anhydrous conditions, the iminophosphorane intermediate that is formed as a result of the Staudinger reaction can react with aldehydes and ketones in an intermolecular fashion (as in the synthesis of imine 36 described above) or intramolecularly with a variety of carbonyl containing functional groups to afford a host of products. Nitrogen containing ring systems such as cyclic imines (44) represent just one of the many products one can prepare and the reaction is particularly well suited for the facile synthesis of five, six, and seven-membered rings. In addition to aldehydes and ketones, carboxylic acids, esters, thio-esters, and amides can also react in an intramolecular fashion to trap an iminophosphorane to afford a variety of heterocycles. Examples from the current literature are described in Section 2.5.5. 

Reactions of Ketones with Methylenephosphoranes.—Intramolecular Wittig reactions have been used to prepare a variety of cyclic compounds including bicyclic alkenes (41) and cyclic imines. In a similar way both Wittig and phosphonate reactions can be used to synthesize many strained bicyclic alkenes (42), but fail with the most strained examples, e.g., (43). Intramolecular Wittig... 

In 2013, the first successful generation of ds-homoenolate equivalents from ds-enals under the catalysis of N-heterocyclic carbene D4 was developed by the Chi group. The ds-homoenolate intermediates I undergo effective reaction with a,p-unsaturated imines to afford chiral cyclic ketones 62. Compared to the trans-enals, ds-enals show different stereoselectivities and new reactivity patterns (Scheme 20.29). 

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