Aryl aldimines

Reaction of p-nitrophenyl 2-(p-tolylsulfinyl)acetate 161 with aryl aldimines in the presence of imidazole was found to give /j-lactams 162 and amides 163206. In the cyclization, only the two 3,4-trans derivatives were formed out of a possible four diastereomeric pairs and, interestingly, the ratio of two diastereomeric pairs went up to 6.7 1. This means not only that internal asymmetric induction207 affords the trans derivative, but that also a relatively high asymmetric induction took place during the reaction. 

Table 1 Reaction of chromium alkoxycarbenes with acyclic aryl aldimines...

Azetidinones.1 The dianion (BuLi) of 1 condenses with the N-aryl aldimine 2 to provide a 1 1 mixture of the trans- and cis-adducts 3. The adducts (3) can be converted by Mitsunobu silylation (inversion), oxidative degradation of the side... 

A new cinchona alkaloid-derived catalyst has been developed for the enantioselective Strecker reaction of aryl aldimines via hydrogen-bonding activation. For reference, see Huang, J. Corey, E. J. Org. Lett. 2004, 6, 5027-5029. 

Akiyama et al. disclosed an asymmetric hydrophosphonylation in 2005 (Scheme 32) [55], Addition of diisopropyl phosphite (85a) to A-arylated aldimines 86 in the presence of BINOL phosphate (R)-M (10 mol%, R = 3,5-(CF3)j-C Hj) afforded a-amino phosphonates 87 in good yields (72-97%). The enantioselectivities were satisfactory (81-90% ee) in the case of imines derived from a,(3-unsaturated aldehydes and moderate (52-77% ee) for aromatic substrates. 

The same group expanded the scope of the aza-Diels-Alder reaction of electron-rich dienes to Brassard s diene 97 (Scheme 37) [60]. In contrast to Danishefsky s diene, it is more reactive, but less stable. Akiyama et al. found chiral BINOL phosphate (R)-3m (3 mol%, R = 9-anthryl) with 9-anthryl substituents to promote the [4 + 2] cycloaddition of A-arylated aldimines 94 and Brassard s diene 97. Subsequent treatment with benzoic acid led to the formation of piperidinones 98. Interestingly, the use of its pyridinium salt (3 mol%) resulted in a higher yield (87% instead of 72%) along with a comparable enantioselectivity (94% ee instead of 92% ee). This method furnished cycloadducts 98 derived from aromatic, heteroaromatic, a,P-unsaturated, and aliphatic precursors 94 in satisfactory yields (63-91%) and excellent enantioselectivities (92-99% ee). NMR studies revealed that Brassard s diene 97 is labile in the presence of phosphoric acid 3m (88% decomposition after 1 h), but comparatively stable in the presence of its pyridinium salt (25% decomposition after 1 h). This observation can be explained by the fact that the pyridinium salt is a weak Brpnsted acid compared to BINOL phosphate 3m. 

In 2006, two groups independently developed an asymmetric Brpnsted acid-catalyzed aza-Diels-Alder-type reaction of iV-aryl aldimines 86 with cyclohexenone 101 to provide isoquinuclidines 102 in good yields (51-84%), endo-diastereoselec-tivities (3 1-9 1), and enantioselectivities (76-88% ee) (Scheme 39). 

Additionally, You reported a F-C reaction of indole with electronically diverse aryl aldimines (Scheme 5.8) [16]. In general, products could be obtained in excellent yields and enantioselectivities in short reaction times. 

In contrast to the epoxides, preparative routes to the aziridines are fairly evenly split between the [C=N + C] and the [C=C + N] routes. Among contributions in the former category, aziridine carboxylate derivatives 110 can be prepared through the lanthanide-catalyzed reaction of imines with diazo compounds, such as ethyl diazoacetate (EDA). In this protocol, iV-benzyl aryl aldimines and imines derived from aromatic amines and hindered aliphatic aldehydes are appropriate substrates <99T12929>. An intramolecular variant of this reaction (e.g.. Ill —> 112) has also been reported <990L667>. 

Cyclic enones such as cyclopentenone or cyclohexanone were inert under the above-mentioned conditions. The reaction of aryl aldimines to cyclic enones can be mediated, however, with the more nucleophilic phosphine 119f [101], although the ee-value of the reactions is usually low (Table 5.17). 

Scheme 5.25 The 119a-mediated aza-MBH reaction of tosyl aryl aldimines with phenyl acrylate and acrolein. EWG = electron-withdrawing group.

The allylation of hydrazones derived from arylalkyl ketones [42] and of N-aryl aldimines in DMF at 0 °C [46] have also been reported. 

General Procedure for the / -ICD-Mediated Asymmetric Aza-MBH Reaction ofTosyl Aryl Aldimines and Methyl Acrylate [44] (pp. 177 and 233)... 

Coupling of aldimines.1 The Ti(II) reagent obtained from TiCl4 and Mg effects reductive coupling of aryl aldimines to 1,2-diarylethylenediamines as a 1 1 mixture of meso- and /-isomers. 

The proximity effect of the functional groups in 47 is instructive. Thus, A-aryl aldimines of the type, ArCH=NAr, are reported to give azoarenes [Ar N=NAr ] and aldehydes [ArCH=0] with DAIB (77IJC(B)376), while phenols are oxidized to quinones, quinol ethers, or quinone acetals, depending on the nature of the reaction medium (92MI2, 01OR327). 

N,N -carbonyldiimidazole. condenses with aryl aldimines to form the (f-lactams 2 in moderate yield. The reaction affords only the two possible tra/t.v-diastcrcomcrs. 

Imine Condensation (Acyl Species to -Lactam). Lithium enolates of acyl 10-diisopropylsulfonamidoisobomeols condense with A-aryl aldimines to give cw-disubstituted (3-lactams with 56-92% ee, accompanied by 2.5-9% of their trans isomers (in... 

A mechanism for the catalytic activity of TBAB in the synthesis of trisubstituted imidazoles may be postulated (Fig. 12.74). The tetrabutylammonium ion probably induces polarization in carbonyl group of aldehydes as well as benzil. Then nucleophilic attack of the nitrogen of ammonia obtained from ammonium acetate, on activated carbonyl, results the formation of aryl aldimine and ct-imino keone. Their subsequent reaction followed by intramolecular interaction leads to cyclization. 

This synthesis is normally carried out in two stages. Firstly, an aryl aldehyde is condensed with aminoacetal to form an aryl-aldimine. This stage proceeds in high yield under mild conditions. Secondly, the aldimine is cyclised by treatment with strong acid hydrolysis of the imine competes and reduces the efficiency of this step and for this reason trifluoroacetic acid with boron trifluoride is a useful... 

Enolizable A -trimethylsilylaldimines can be generated in situ by the addition of organolithium reagents to bis(trimethylsilyl)formamide. These undergo addition reactions with enolates to form 3-lactams. Phosphonium salts used in catalytic amounts promote the reaction between aryl aldimines and silylketene acetals to form 3-amino esters. Mannich bases with N-2-hydroxyethyl-N-methyl substitution are prepared by the reaction of the iminium salt synthon, 3-methyl-1,3-oxazolidine, with enol silanes in the presence of chloromethylsilanes. ... 

Hoffmann et al have reported the addition of allyl(dimethoxy)borane to linear and branched a-aryl-aldimines (entries 16-19, Table 2). The absence of a-deprotonation may be explained by a delicate balance between the basicity and the reactivity of the allylboronate. Allyl(dimethoxy)borane should thus be considered the reagent of choice in reactions with enolizable aldimines. Reactions are conveniently carried out at 25 °C in CH2CI2 and work-up is performed using triethanolamine to break up amine-boronate complexes. Allyl(dimethoxy)borane also adds to the cyclic imine, A -piperideine, in 90% yield. The reported yields for the addition of allyllithium and allylmagnesium chloride to A -piperideine are low. 

Diels-Alder reaction Allylsilanes and propargylsilanes condense with A-aryl-aldimines in the presence of Gads to provide 2,4-disubstituted tetrahydroquinolines and quinolines, respectively. 

The enamine catalysis detailed above proceeds via activation of the Mannich donor. An alternate strategy to the catalysis of the Mannich reaction is by the use of Brensted acids that activate the acceptor imine by protonation on nitrogen. Some of the most successful asymmetric variants of this process use BINOL-based phosphoric acids as catalysts. For instance Terada and coworkers used (7.144) to effect highly enantioselective addition of acetylacetone to a range of aryl aldimines ... 

Oxidation of Imines. The oxidative rearrangement of A -aryl-aldimines leads to amides upon treatment with m-CPBA and BF3 OEt2 (eq 51). The reaction presumably proceeds via the Lewis acid mediated peracid imine adduct which then loses m-chlorobenzoic acid. 

This reaction usually works for nonenolizable imines (e.g., A -aryl aldimines) and has the features of readily accessible starting materials, and simple preparation of 3-substituted or unsubstituted 2-azetidinones (i.e., 3-lactams) with direct control of stereoselectivities. It has been reported that the yield of this reaction depends on the activation and the type of zinc. The stereochemistry of /3-lactams depends on the a-substituent of bromoacetates, the solvent, and the alkyl portion of the esters. For example, when the a-substituent is an alkyl group (e.g.. Me, Et, /-Pr, cyclohexyl, r-Bu), the major product has cis geometry, such a trend is especially prevailing for the reaction of acetate with a branched a-substituent (e.g., j-Pr, cyclohexyl, r-Bu) in THF. s For comparison, the reaction of isopropyl acetate in toluene tends to form jS-lactams of trans geometry. In addition, phenyl acetates favor the trans isomers regardless of the solvents. ... 

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