A-Iminoesters

Scheme 18 Reagent-induced enantioselective catalytic synthesis of 2,3-diamino esters by addition of a-amino and a-iminoester enolates to imines...

The electroreductive cyclization of chiral aromatic a-iminoesters 175, prepared from ( )-a-amino acids such as (6)-valine, (A)-leucine, and ( -phenylalanine, in the presence of chlorotrimethylsilane and triethylamine afforded mixed ketals of ar-2,4-disubstituted azetidin-3-ones 176 stereospecifically (>99% de and 85-99% ee) (Equation 46) <2003JA11591>. The best result was obtained using tetrabutylammonium chlorate as a supporting electrolyte and a platinum cathode. 

An enantioselective version of this reaction has been reported by Rueping et al.102 Treatment of an a-iminoester and an alkyne with silver acetate and a binol phosphate derivative gave propargylic amines with the highest enantiomeric ratio (er) reported as 96 4. Although the proposed catalytic cycle invoked the in situ formation of the... 

In addition to a-ketoesters, a-iminoesters were successful as substrates, allowing the synthesis of a-amino acid derivatives [equation (7.9)].119 Exposure of 157 to gem-dimethylsilacyclopropane 89 and substoichiometric amounts of silver tosylate produced azasilalactone 158. In contrast to the above-mentioned synthesis of 154, hydrolysis of 158 was not observed on aqueous extraction. The authors attributed the enhanced robustness of 158 to the steric bulk of the anisidine group. 

More recently, Benaglia and coworkers reported that the allylation reaction of a-iminoesters proceeded to give the homoallyl alcohols with moderate enantioselectivities (Scheme 9.4).9 The chiral diimine that has a chiral 1,2-cyclohexyldiamine framework was used as the ligand. The reaction of a-iminoesters and allyltributyltin in the presence of AgOTf and diimine ligand proceeded to afford chiral amino acid derivatives with moderate enantioselectivities. 

In 1998, Lectka and coworkers reported the asymmetric Mannich reaction of a-iminoesters catalyzed by a BINAP-Ag(I) complex (Scheme 9.14).25... 

Similarly, terminal alkynes added to a-iminoesters derived from ethylglyoxylate in the presence of silver salts.100 In this case, the reaction worked best in apolar solvents (Scheme 10.64). 

The C=N bond of simple imines possesses modest reactivity toward intermolecular radical additions, so such acceptors have rarely been exploited. To enhance their reactivity toward nucleophilic radicals, electron-withdrawing groups at the imine carbon have been effective, as demonstrated by Bertrand in radical additions to a-iminoesters prepared from chiral amines [25]. Also, more reactive oxime ethers have been exploited extensively for radical addition, mainly through the longstanding efforts of Naito [26]. In most cases, stereocontrol has been imparted through the substituents on the imino carbon chiral O-substituents on oximes for stereocontrol were ineffective, presumably due to poor rotamer control [27, 28]. 

Similarly, trifluoropyruvates and related a-iminoesters represent 1,2-dielectrophilic building blocks. With anilines and phenols they undergo C-aklylation in an o-position followed by ring closure to form y-lactams and 7-lactones (86BAUI895 87BAU2332, 87BAU2646 89BAU1512) (Scheme 28). 

Irradiation of W10O324 or PW12O403, alkanes, and methyl cyanoformate in MeCN solution produces either the corresponding nitriles or a-iminoesters with high selectivity, depending on the temperature, via a mechanism involving two roles for the polyoxotungstate Initial report on sub- 378... 

A cationic copper complex with (K)-tol-BINAP as chiral auxiliary catalyzes asymmetric addition of allenyltin and propargyltin compounds to a-iminoesters to produce, preferentially, propargyl and allenyl adducts, respectively, in moderate to high enantioselectivity (Scheme 12.32) [83]. 

Hoveyda et al. [262] prepared different N-aryhnaleimidobenzoic acids linked to SASRIN resin, whose double bond present in the maleimido moiety could act as a convenient dipolarophile in cycloaddition reactions. Thus, solution-generated a-iminoesters (from different aromatic aldehydes and aminoesters) were reacted vdth the supported maleimides (158) under Tsuge [263] conditions. Formation of the expected syn-endo cycloadduct (160) was observed after only 1 h at room temperature (Scheme 33). From structure-reactivity analysis, the authors concluded that the cycloaddition reaction is more sensitive to steric then to electronic factors on the azomethine yhde counterpart. The advantage of this procedure stems essentially from the fact that the iminoesters (159) are formed in situ. Aldehydes containing a-hydrogens could also be employed. Moreover, the resin in this case also plays the role of a protective group, because, in contrast with N-alkyl and N-aryl (see above) maleimides, N-unsubstituted maleimide is not suitable for 1,3 dipolar cycloadditions. 

In particular, defluorination brought about by the Mg-TMSCl-DMF system is reliable for the purpose [11]. Difluoroenol silyl ethers [12], enamines [13], phenyl-1,1-difluoroacetate [14], difluorinated Danishefsky diene [15], and trimethylsilyldifluoromethyl benzenes [16] can be prepared in good to excellent yields. The one-pot synthesis of 22 from 21 is of great interest. Defluoro-dechlorinative double silylation occurs under very mild conditions to afford compound 22, a useful synthetic intermediate, in which two different silyl groups can be replaced with various electrophiles in a stepwise manner [17]. Highly functionalized a-iminoesters (27) can be synthesized via 25 and 26 in excellent yields as shown in Scheme 2.15. 

The cycloaddition of in sitM-generated azomethine yhdes with electron-deficient alkenes is a useful method for the generation of stereodefined, substituted pyrrolidines, and there has been some recent interest in the development of a catalytic asymmetric variant. While a variety of methods for the generation of azomethine ylides have been developed, treatment of an a-iminoester (8.200) with an amine base in the presence of metal salts is the process most commonly employed in the asymmetric variant, which generally uses an enantiomerically pure metal complex of copper, silver or zinc to give an N-metallated ylide (8.201) (Figure 8.6). ... 

Scheme 17.8 Mannich reaction of propanal with an a-iminoester.

The reaction of allyl-9-BBN with a-iminoesters in which (S)-(-)-a-methyl-benzylamine is utilized as the chiral source produced the corresponding amino acid in high chemical (92%) and optical (92% ee) yield. These are increased to 96% when (-)-l-cyclohexylethylamine is employed. The reaction of allylzinc or magnesium or titanium reagents, on the other hand, has resulted in lower or negligible ee s. 

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

The Pd-catalysed cross-coupling ethoxycarbonylation of aryl boronic acids with A-aryl-a-iminoesters has been shown to give aryl carboxylic esters via carbonyl-imino a bond cleavage and involve a 1,2-aryl shift (Scheme 138). ... 

The acidic NH proton of the sulfonamide group in chiral organocatalyst 41 turned out to be of key importance for both aspects of selectivity, an anti/syn ratio >20 1 and e.e. >99 %. The mechanism of this reaction comprises an intermediary formation of enamine between the aldehydes and chiral catalyst and protonation of a-iminoester. In the transition state two reactants are oriented in parallel planes affording anri-isomers of TM 4.18a-e in (25,37 )-absolute configuration (Fig. 4.6). 

Coupling of Aldehydes or Imines and Alkynes. Among the silver salts screened, silver nitrate and -triflate proved to be the most efficient catalyst for the condensation of terminal alkynes with an a-iminoester derived from ethyl glyoxylate (eq 55). ... 

A purely ionic hydrogen bond activation mechanism might be involved in the aza-Henry reaction between a-iminoesters, a very reactive subclass of imines, and various nitroalkanes catalyzed by the BINOL phosphoric acid 44 [54]. The corresponding P-nitro-a-amino acid esters were produced in good yields, diastereo- and enantioselectivities (Scheme 29.23). The authors postulated a dual role of catalyst 44 through activation of the a-iminoester by protonation and control over the nitroaUcane/nitronate equilibrium (Scheme 29.24). 

Scheme 29.23 Enantioselective aza-Henty reaction of a-iminoesters catalyzed by 44, and representative examples.

The microwave-assisted solvent-free intramolecular cyclization of a-iminoester derivatives leads to the synthesis of a number of seven, eight and ten membered lactams (Zradni et al., 2007). The yield was 70-85% in 15-35 min under microwave irradiation while it takes about 108 h at 140-170°C under conventional condition. 

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