Activations imines

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Bronsted-acid-catalyzed Diels-Alder reactions are not frequent because of the proton sensitivity of many dienes and cycloadducts, especially when long reaction times and high temperatures are required. Examples in aqueous medium involving imines activated by protonation as dienophiles and a proton-promoted Diels-Alder reaction of glyoxylic acid with cyclopentadiene are considered in Section 6.1. 

Recently, several research gronps reported on the use of chiral BINOL phosphates as Brpnsted acid catalysts in MCRs involving imine activation. 

The presence of a heteroatom directly connected to the nitrogen atom of the imine activates it toward hydrogenation, while creating a second coordination site for the catalyst. Indeed, some successful results have been achieved for the hydrogenation of N-acylhydrazone, sulfonimide, and N-diphenylphosphinyl ketimines. The Et-DuPhos-Rh complex is an efficient catalyst for the asymmetric hydrogenation of a variety of N-acyl- ... 

A mild, acid- and metal-free direct reductive amination of ketones has been achieved that relies on selective imine activation by hydrogen bond formation and utilizes the Hantzsch ester for transfer hydrogenation and catalytic amounts of thiourea as hydrogen bond donor. The mechanism in Scheme 18, supported by ab initio calculations, has been suggested.358... 

Piperidones. The dianion (2) of 1 reacts with imines activated by BF3 etherate to afford, after cyclization (TFAA), substituted 2-piperidones (3). These lactams can be converted to substituted piperidines (S) by desulfonation and LAH reduction.1... 

Aza Diels-Alder reactions of nonactivated imines have been investigated with regard to the effects of electronically neutral substituents and the influence of Lewis acids [179, 180]. Some of the synthetic applications described below nevertheless take use of the higher reactivity of iminium ions or imines activated by electron-withdrawing substituents, respectively. 

Numerous further chiral imines activated by electron-withdrawing substituents have been investigated in order to carry out stereoselective aza Diels-Alder reactions. In these studies, Bailey et al. have recently introduced the use of two inducing stereocenters in the imine. This approach proved to yield excellent diastereoselectivities thus, imine 3-12 bearing a (,R)-8-phenylmenthyl auxiliary gave the essentially pure cycloadduct 3-13 upon hetero Diels-Alder reaction with cyclopentadiene (Fig. 3-4) [194-196]. 

Crotyltins react regioselectively with a-alkylimines to give exclusively branched products with an excellent syn/anti selectivity up to 30 1, when the imine activation is conducted at —78 °C prior to the addition of the crotyltin. This selectivity which is consistent with an acyclic transition state is rapidly fading when operating at a higher temperature. This would be the result of an equilibrium between the two imine/Lewis acid complexes (equation 14). There are very few examples with a, /3-unsaturated aldimines, but it has to be noted that under TiCU activation, they are able to undergo a double nucleophilic addition of ketene silyl acetal and allyltributyltin to give the homoallylic amine in a reasonable yield . 

Aqueous reductions are useful for amine synthesis. Organic reducing agents (N H or formic acid) reduce amides or imines . Active metals in acid reduce nitro groups . Reduction of Ph3PNBr with I ... 

The first systematic investigation toward Lewis acid catalyzed vinylogous Mukaiya ma Mannich reactions was reported by the group of Ojima in 1987 who showed that acyclic vinylketene silyl 0,0 acetals 10 reacted with imines activated by stoichio metric amounts of TiCU to furnish either 5 amino 2 alkenoates 11 or 5,6 dihydro pyridones 12 selectively in excellent yields depending upon the substitution of the silyl dienolate employed (Scheme 5.4) [5]. Although 2 methyl substituted vinylketene acetal 10a gave rise to acyclic 5 amino 2 alkenoates 11 exclusively, 3 methyl substi tuted vinylketene acetal 10b furnished 5,6 dihydropyridones 12 as the sole products. 

France S, Shah MH, Weatherwax A, Wack H, Roth JP, Lectka T (2(X)5) Bifunctioneil Lewis acid-nucleophile-based asymmetric catalysis mechanistic evidence for imine activation working in tandem with chiral enolate formation in the synthesis of p-lacttuns. J Am Chem Soc 127 1206-1215... 

From the many examples of reactions with imines activated in various ways, we select the asymmetric synthesis of pipecolic acids by double diastereomeric induction using an activated imine 87 with two chiral auxiliaries - a-methylbenzylamine on the nitrogen atom and 8-phenylmenthol as esterifying group. Both these auxiliaries were discussed in earlier chapters (22 and 27). Acid-catalysed cycloaddition with normal dienes gives excellent asymmetric induction and reasonable yield. We show the matched case - the mismatched case is obviously worse.13... 

A new pathway for catalytic aziridination was uncovered recently by Brookhart and Templeton [30]. Standard Lewis acids such as BF3, AICI3, and TiCl4 were found to promote the reaction of ethyl diazo acetate with imines to generate the corresponding aziridines in good yield. A simple mechanism involving imine activation and alkylation by the diazo compound was advanced to account for this result (Fig. 6). 

One synthetic problem in the imino Diels-Alder reactions is the imines stability under the influence of Lewis acids. It is desirable that the imines activated by Lewis acids are immediately trapped by dienes or dienophiles [57]. In 1989, Sis-ko and Weinreb reported a convenient procedure for the imino Diels-Alder reaction of an aldehyde and a 1,3-diene with M-sulfinyl p-toluenesulfonamide via N-sulfonyl imine produced in situ,by using a stoichiometric amount of BF3.OEt2 as a promoter [64]. 

Taking imine activation as an example, the relative roles of proton transfer/ ion-pairing versus hydrogen bonding have been probed for Brpnsted acid catalysis. Taking simple diaryl ketimines and aldimines as model substrates and... 

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