Subject aldimines

Anilines react with ct-haloacetophenones to give 2-arylindoles. In a typical procedure an W-phenacylaniline is heated with a tw o-fold excess of the aniline hydrobromide to 200-250°C[1]. The mechanism of the reaction was the subject of considerable investigation in the 1940s[2]. A crucial aspect of the reaction seems to be the formation of an imine of the acetophenone which can isomerize to an aldimine intermediate. This intermediate apparently undergoes cyclization more rapidly (path bl -> b2) than its precursor (Scheme 7.3). Only with very reactive rings, e.g, 3,5-dimethoxyaniline, has the alternative cydiz-ation (path al a2) to a 3-arylindole been observed and then only under modified reaction conditions[3],... 

To a solution of aldimine 1 (0.01 mol) in acetone, added ethyl-a-mercapto/a-cya-noacetate (0.01 mol) followed by basic alumina (20 g) with constant stirring. The reaction mixture taken in a beaker, was thoroughly mixed and the adsorbed material was dried in air. The adsorbed reactant in the beaker was placed in an alumina bath and subjected to microwave irradiation for 1-2 min. On completion of the reaction as followed by TLC examination, the mixture was cooled to room temperature and the product was extracted into acetone (3x15 mL). Recovering of solvent under reduced pressure yielded the product, which was purified by recrystallization from the mixture of ethanol-acetone. 

The synthesis of novel azetidine derivatives remains the subject of intensive study. New procedures for the preparation of this class of compounds include, e.g., rearrangement of /3,7-aziridino-a-amino esters <2007OL4399>, copper-catalyzed multicomponent reactions of terminal alkynes, sulfonyl azides, and carbodiimides <20070L1585>, regioselective addition of 1,3-dicarbonyl dianions to iV-sulfonyl aldimines <2007T4779>, elaboration of a-amino acids <2007TL2471>, palladium-catalyzed iV-arylation of azetidines <2007S243> and... 

The formation of 49 is strong evidence that aldimine 48, like other aldimines, is a reactive sulfur acceptor and that thiaiziridine 51 is a likely intermediate in this reaction that undergoes an intramolecular stabilization via its ring opening accompanied by a hydrogen shift. The claimed intermediacy of thiaziridine 50 derived in this case, from ketimine 52, cannot be denied since, if formed, it would have been subjected to a sulfur extrusion. 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

Compared with aldehydes and ketones, aldimines and ketimines are less reactive towards nucleophilic addition. Furthermore, imine additions are subject to steric constraints, and rapid deprotonation proceeds with imines bearing ot-hydrogen atoms. The Lewis acid promoted addition methodology has provided a solution to these problems. 

AllyUUion. The addition of an allyl group to polymer-bound aldimines is subject to 1,3-asymmetric induction. 

Addition to imines. Functionalized secondary amines are formed by addition of hydrazones and diazo compounds to aldimines, and these reactions are subject to asymmetric induction by 1. 

Strecker reaction to establish a new stereocenter is subject to asymmetric induction, capable of creating either a tertiary" or quaternary carbon atom in the presence of 59. The peptido-imine 60 proves to be an excellent ligand for the Ti(IV)-mediated cyanation of aldimines. On catalysis of the bicyclic guanidine 61 the addition of HCN to A-benzhydrylaldimines affords a-amino nitrile derivatives with moderate to good ee. ... 

These favourable results can probably be traced back to the stable chelates formed by the lithium salts of the aldol adducts. In the hydrolysis product the nitrogen of the aldimine group is linked through an intramolecular hydrogen bond bridge, as was established by the IR spectrum. Since the aldimine adduct could finally be converted by treatment with acid in a nearly quantitative yield to 3-phenylcinnamaldehyde, the preparative problem of subjecting aromatic ketones to the directed aldol condensation was solved. 

In general, the aldimine adducts of natural products can be converted in one step to the corresponding a, /S-unsaturated aldehydes or ketones. They are subjected to a steam distillation in the presence of oxalic acid, in which the final product distils over. Under these conditions the more thermodynamically stabile product is formed, usually the trans olefin. 

Figure 11.13 Reactions at a-carbon of a-amino acids catalyzed by pyridoxal enzymes All three substituents at C are subject to labilization in the three types of a-carbon reactions. The hydrogen is labilized in recemization reactions, the amino group is labUized in the transamination and the carboxyl group is labilized in decarboxylation. a-Amino acid condenses with pyridoxal phosphate to yield pyridoxylidene imino acid (an aldimine). The common intermediate, aldimine and distinct ketimines leading to the production of oxo-acid (in transamination), amino acid (in racemization) and amine (in decarboxylation) are shown. The catalytic acid (H-A-) and base (-B ) are symbolic both can be from the same residue such as Lys258 in aspartate aminotransferase.

Peddinti also reported a simple and efficient one-pot synthesis of benzoxazolic bicyclo[2.2.2]octenones 29-31 by subjecting 2-methoxy-substituted phenolic aldimines of type 26 to a similar treatment with DIB in the presence of the same kind of dienophiles 24, or furans, in MeOH [47], This clever domino reaction starts with a DIB-mediated oxidative cychzation of the phenolic aldimines into the phenolic benzoxazoles 27, which are then converted, with a second equivalent of DIB, into the MOBs 28 that are finally trapped with excess of dienophile to furnish selectively the expected [4+2] cycloadducts 29-31 (Fig. 11) [47]. 

To better understand the mode of action of pyridoxal-P, let us examine in detail equation 7-3 the conversion of homosereine phosphate to threonine. It is an elimination-hydration transformation. The first process (Fig. 7.10) involves an aldimine ketimime tautomerization which is subjected to general-acid catalysis intramolecularly by the hydroxyl group, followed by the slow breaking of a C—H bond. The latter is the rate-determining step. 

Following advances made in reduction reactions (vide supra), hydroboration and diboration have been the subject of intense investigation with NHC-Cu catalysts. Early work by Sadighi revealed that [(ICy)Cu(Ot-Bu)] efficiently catalyzed the 1,2-diboration of aldehydes. Mechanistic studies permitted to rationalize a number of features of this reaction and notably ruled out a possible oxidative addition pathway to favour c-activation of the diboron reagent by the copper centre. [(ICy)Cu(Ot-Bu)] was also used for the diaster-eoselective diboration—in fact, hydroboration after work-up—of sulfinyl aldimines. ... 

Atropisomeric thiourea catalyst (14) has been developed and subjected to hydro-cyanation of aldimines (Scheme 2.32) [102]. 

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