Imino-aldol reaction

Similarly, the addition of an amine to the enone moiety can initiate a domino process leading to substituted diaminocyclohexanes [34]. In this transformation an imino aldol reaction occurs. The observed stereoselectivity was again >95 5, and the yield between 51 % and 69% in all cases. 

Amberlyst 15 DRY, a sulfonic cation exchange resin with a large surface area, was found to catalyze the imino aldol reaction of imines with ketene silyl acetals to provide racemic y9-amino esters in yields up to 99% [104]. 

Kobayashi S, Akiyama R, Moriwaki M, Three-component or four-component coupling reactions leading to 6-lactams, Facile synthesis of y-acyl-6-lactams from silyl enolates, a, /l-unsaturated thioesters, and imines or amines and aldehydes via tandem Michael-imino aldol reactions, Tetrahedron Lett., 38 4819—4822, 1997. 

Kobayashi et al. also published experiments in which they applied polymer-bound rare earth metal triflates [9], The performance of Lewis acid-catalyzed imino-aldol reactions at the solid phase was realized by linking the silyl enolethers u5-(4 -chloromethylphenyl)pentylpolystyrene[10]. 

Lewis acid-catalyzed tandem Michael imino-aldol reactions enable the one-pot synthesis of 7-acyl-(5-lactams from a, j6-unsaturated thio-esters, silyl enolates and imines [15]. For the initial Michael addition, the combination of SbClj with Sn(OTf>3 (5 mol %) proved to be efficient. However, after the addition of the imino compound the iminoaldol product was isolated in moderate yield. For the enhancement of turnover and yield, Sc(OTf)3, once again proved to be the Lewis acid of choice (Scheme 4, 15 16 = 81 19, 94%). 

The same anchor group is realized on a 5-(4 -chloromethylphenyl)-pentyl-PS/DVB (CMPP resin). R is introduced as R-COSK. Lewis acids can be used during synthesis without decomposition or deactivation (e.g. Sc(OTf)3-catalyzed imino aldol reaction) [322]... 

However, a catalyst made by microencapsulating scandium triflate in polystyrene was easy to recover and reuse with no loss in activity by filtration. In the imino aldol reaction (6.11), its activity was greater than that of the unencapsulated counterpart, maintaining activity (90% yields) after seven cycles 55 (Many Lewis acids do not work well in this reaction.)... 

Scheme 16. Imino aldol reaction (flow system)...

Aldol and imino-aldol reactions. A Yb complex prepared from YbfOTflj and a C -symmetric a,a -bistriflamidobibenzyl has been used in the Mukaiyama aldol reaction," resulting in moderate asymmetric induction. Imines are activated toward enol derivatives, such as ketene silyl ethers. iV-(a-aminoalkyl)benzotriazoles are suitable surrogates of imines. One-pot syntheses of p-amino esters and ketones can also be achieved. 

An imino aldol reaction catalyzed by a cation-exchange resin [31], and uncatalyzed aldol addition of enoxysilacyclobutanes to aldehydes [32] have also been reported. 

Imino aldol reaction of ketene silyl acetals with the chiral imine derived from tartaric acid 83 in the presence of a cation-exchange resin provided the corresponding /i-amino esters 84 in a good yield and high diastereose-lectivity [68]. The esters 84, thus obtained, were subjected to the Grignard reagent which promoted S-lactam formation. After a sequence of reactions compound 84 was transformed into the ester 85 [68] which in the past was... 

Lewis Acid Catalyzed Reactions. S amarium iodide catalyzes several transformations by presumably acting as a Lewis acid. For example, it is an efficient catalyst for the imino-Diels-Alder (eq 70) and for imino-aldol reactions. Tandem Mukaiyama-Michael-aldol (eq 71) and Michael imino-aldol processes have also been reported. ... 

There are surprisingly few common approaches to the lupin indolizidines and their quinolizidine homologs despite their structural similarity. One such approach was recently reported by Cutter et al., who used imino—aldol reactions of phenyl 5-chlorovalerate (992) as the starting point for the synthesis of both (—)-tashiromine (ent-929) and (—)-epilupinine (ent-921) (Scheme 123). " The addition of the hthium enolate of 992 to the (S)-N-sulfinylimine (- -)-993 proved to be highly diastereoselective, giving a 78% yield of the adduct (- -)-994 and its (S,S)-isomer (+)-995 in a ratio of 16 1. The stereochemistry of 994 was confirmed by X-ray diffraction. 

Yamamoto and coworkers have also shown that tris(pentafluorophenyl)borane is a highly active catalyst for analogous imino-aldol reactions. Here, both the N-trialkylsilyl imines (72) (Equation 46) [44] and the N-benzyl imines (73) (Equation 47) [45] are applicable as electrophiles with ketene silyl acetals (74), and the reaction gives remarkably high yields of the N-benzyl imino-aldol adducts. 

Imines also serve as electrophiles for the imino-aldol reaction to produce aminocarbonyl compounds that are important synthetic precursors of yff-amino acids, ji-amino alcohols, and y lactams. Accordingly, various types of catalytic asymmetric Mannich-type reactions have been studied and invented with chiral Lewis acid catalysts like 13 14 containing Fe, Cu, Zn, Zr, Ag, or or organocatalysts... 

Ghorai MK, Ghosh K, Yadav AK. Enantioselective synthesis of a, p-diamino ester derivatives memory of chirality in imino-aldol reactions. Tetrahedron Lett. 2009 50 476-479. 

A highly stereoselective synthetic strategy for disubstituted piperidines 247 with cis appendages was reported recently. A one-pot intermolecular imino aldol reaction of a-arylmethylidine 244 or a-alkylidine p-keto ester 248 with aldimine 246 followed by intramolecular aza-Michael reaction (alkylative cyclization) in a domino fashion afforded the corresponding piperidines 247 in high yields and excellent stereoselectivity (er, dr >99%) (Scheme 40.54). ... 

Scheme 11. The stereoselective tandem imino-aldol reaction...

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