Esters a-imino

For imines, a-imino esters with an N-p-methoxyphenyl substituent (21b) also reacted with Danishefsky s diene in the presence of 10 mol% of CUCIO4-T0I-BINAP to give the corresponding adduct in high yield with good enantiomeric excess (Scheme 5.10). Remarkably, reverse enantioselectivity was observed when the a-imino esters 21a and 21b were used. This notable selectivity was explained by as-... 

A chiral magnesium catalyst prepared from magnesium iodide and 1,2-diphenyl-ethylenediamine was also found to he effective in asymmetric aza Diels-Alder reaction of a-imino ester 21b with 7a (Scheme 5.12) [32]. The novel catalyst was discovered using parallel comhinatorial methods. 

Aza Diels-Alder Reactions of a-Imino Esters with Dienes 203... 

Chan et al. reported a similar reaction, that is, Ag(l)-catalyzed alkynylation of a-imino esters (Table 10).520 The ft,7-alkynyl ct-amino acid derivatives were obtained in high yields. 

Table 10 AgOTf-catalyzed addition of terminal alkynes to a-imino ester...

Besides these results, we registered with interest the first example of a Pd-bi-nap-catalyzed hydrogenation of a fluorinated a-imino ester in the presence of trifluoroacetic acid in fluorinated alcohols (with ee-values up to 91%, but very low TON and TOF) [42]. 

Ferraris et al.108 demonstrated an asymmetric Mannich-type reaction using chiral late-transition metal phosphine complexes as the catalyst. As shown in Scheme 3-59, the enantioselective addition of enol silyl ether to a-imino esters proceeds at —80°C, providing the product with moderate yield but very high enantioselectivity (over 99%). 

Ferraris et al.109 also studied the diastereoalkylation of a-imino esters catalyzed by Cu complexes. As depicted in Scheme 3-60, the reaction results in both high diastereoselectivity (syn/anti up to 21/1) and high enantioselectivity for the major product (ee up to 99%). 

Jorgensen s group reported the aza Diels-Alder reactions in the presence of several chiral catalysts.52 They found that chiral bis(oxazoline) ligands 81, 83, 103, 104, and 105, which were effective in asymmetric oxo hetero Diels-Alder reactions, induced the aza Diels-Alder reaction of a-imino ester with Danishefsky s diene with only poor to moderate enantioselectivity. Selected results are listed in Scheme 5-40. 

On the other hand, the combination of Tol-BINAP with CUCIO4 has been shown to be very effective for aza Diels-Alder reactions. As shown in Scheme 5-41, moderate yield and good to excellent enantioselectivity can be obtained in the reaction of a-imino ester with diene 91 or 100. 

Amino acid synthesis (cf. 12,15). The reaction of 1 with chiral a-imino esters provides an enantio- and diastereoselective synthesis of amino acid derivatives. The imine (2), prepared from (S)-phenethylamine, reacts with 1 to give 3, which... 

Lectka and co-workers found that cationic Cu phosphine complexes are efficient Lewis acids in the activation of a-imino esters (248). The Tol-BINAP was found to be the most effective ligand providing the adduct of acetophenone enol-... 

Similarly, reactions of 115 with the a-imino ester 119 gave corresponding allenyl-amino acid esters 120 as the main produds [102]. The SE2 readions were catalyzed by a copper species (1 mol%), which was generated from [Cu(NCMe)4]C104 and (R)-tol-BINAP, and showed good enantio- and regioseledivity (Scheme 3.61). 

The diastereofacial selective imine-ene reactions with a-imino esters prepared from (—)-8-phenylmenthyl glyoxylate have provided an efficient entry to the asymmetric synthesis of a-amino acids, and a Lewis acid-mediated intramolecular imine-ene reaction has been used for the key spirocyclization step in a recent synthesis of (—)-perhydrohistrionicotoxin. Asymmetric azo-ene reactions have been effected using the chiral azo-enophile, di-(—)-(lR,2S)-2-phenyl-l-cyclohexyldiazenedicarboxylate. ... 

Aldol reactions of silyl enolates are promoted by a catalytic amount of transition metals through transmetallation generating transition metal enolates. In 1995, Shibasaki and Sodeoka reported an enantioselective aldol reaction of enol silyl ethers to aldehydes using a Pd-BINAP complex in wet DMF. Later, this finding was extended to a catalytic enantioselective Mannich-type reaction to a-imino esters by Sodeoka s group [Eq. (13.21)]. Detailed mechanistic studies revealed that the binuclear p-hydroxo complex 34 is the active catalyst, and the reaction proceeds through a palladium enolate. The transmetallation step would be facilitated by the hydroxo ligand transfer onto the silicon atom of enol silyl ethers ... 

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

In 2008, the Rueping group reported the addition of nitroalkanes 78 to A-PMP-protected a-imino esters 79 in the presence of chiral phosphoric acid (R)-14r (10 mol%, R = SiPhj) (Scheme 29) [51]. This transformation provided P-nitro-a-amino esters 80 in good yields (57-93%), anrt-diastereoselectivities (2 1-13 1) and enan-tioselectivities (84-92% ee). 

Rueping has recently reported an interesting alknylation reaction of a-imino esters employing both phosphoric acid Ip and AgOAc as orthogonal cocatalysts [35]. As seen in the catalytic cycle in Scheme 5.21, generation of chiral iminium ion pair I nucleophilic and alkynyl-silver species II proceeds simultaneously. Subsequent nucelophilic addition completes both parallel cycles [36]. 

For a related highly enantioselective reduction of a-imino esters with a BINOL-derived phosphoric add diester, see Kang, Q., Zhao, Z.-A. and You, S.-L. (2007) Adv. Synth. Catal., 349,1557-1660. 

It was also reported that diastereo- and enantioselective Mannich reactions of activated carbonyl compounds with a-imino esters were catalyzed by a chiral Lewis acid derived from Cu(OTf)2 and a bisoxazoline (BOX) ligand [31] [(Eq. (6)]. Catalytic enantioselective addition of nitro compounds to imines [32], and aza-Henry reactions of nitronates with imines [33] also proceeded under similar reaction conditions. 

Phase-transfer-catalyzed direct Mannich reaction of glycine Schiff base 2 with a-imino ester 79 was achieved with high enantioselectivity by the utilization of N-spiro chiral quaternary ammonium bromide le as catalyst (Table 5.14) [42],... 

Table 5.14 Direct asymmetric Mannich reaction of2 with a-imino ester under phase-transfer conditions.

Two examples of such applications are outlined in Scheme 3. In the first one imidazolidinone la 10 mol% catalyzed the conjugated addition of a plethora of variously substituted N,N-disubstituted anilines to ,/fun saturated aldehydes to afford highly enantiomerically enriched /3-aryl aldehydes 5 (ee 89-97 %) in good yields (>73 %) [3]. On the other hand, the use of cationic BINAP-Cu complexes 6 (1-5 mol%) was found to be effective in the stereocontrolled 1,2-addition of indoles to the N-tosyl-a-imino ester 7 in TFIF at -78 °C [4]. 

The chiral Cu(OTf)2/BOX complexes 8 and 9 are also catalysts of asymmetric Mannich-type additions of unmodified malonates and /3-ketoesters to activated N-tosyl-a-imino esters [22]. 

The phase-transfer-catalyzed direct Mannich reaction of 28 with a-imino ester 64 was achieved with high enantioselectivity by using 32e as catalyst (Scheme 4.23) [63]. This method enables the catalytic asymmetric synthesis of differentially protected 3-aminoaspartate, a nitrogen analogue of dialkyl tartrate, the util-... 

In a similar fashion, Lectka et al 2X have developed the silver-catalyzed enantioselective alkylation of a-imino ester 378 by treatment with silyl enol ethers in the presence of AgSbF6 and (i )-BINAP, giving the amino acid derivatives 379 in good to high yields and enantioselectivities (Scheme 110). The analogous ene reaction of substrate 378 with 2-phenyl-propene afforded the corresponding unsaturated amino ester with 71% ee.322... 

In general, differently substituted alkyl and aryl ketimines, including a-imino esters, can be reduced in good to excellent yields (Table 1). 

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