Imine enantioselective coupling

Miller and co-workers have reported the use of thiazolylalanine-derived catalyst 65 to render the aldehyde-imine cross-coupling enantioselective [56]. The authors comment on the time sensitivity of this transformation and found that racemization occurs when the reaction goes to complete conversion. Electron-deficient aldehydes are the most efficient couphng partners for various tosylamides leading to the corresponding products 66, 68, and 69 (Scheme 8). 

Scheme 9.28. Ni-catalyzed enantioselective coupling of alkynes, imines, and triethylborane.

Mennen MS, Gipson JD, Kim YR, Miller SJ (2005a) Thiazolylalanine-derived catalysts for enantioselective intermolecular aldehyde-imine cross-couplings. J Am Chem Soc 127 1654... 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the thiazolylalanine-derived catalyst 191 for asymmetric intramolecular Stetter reaction of a,P-unsaturated esters <05CC195>. However, these cyclizations proceed only in moderate enantioselectivities and yields even under optimized conditions. Thiazolium salt 191 has been used successfully for enantioselective intermolecular aldehyde-imine cross coupling reactions <05JA1654>. Treatment of tosylamides 194 with aryl aldehydes in the presence of 15 mol% of 191 and 2... 

Shintani and Fu repored enantioselective coupling of terminal alkynes 420 with azomethine imines 419 by copper-catalyzed [3 + 2]-cycloaddition (Scheme 133).195 In the presence of Cul and phosphafer-... 

Miller and coworkers have performed kinetic studies on a pyridylalanine-peptide catalyzed enantioselective coupling of allenoates 16 and N-acyl imines 17 to investigate the mechanism of the aza-MBH reaction [20]. In the catalytic cycle of a typical MBH/aza-MBH reaction, the proton transfer step or C-C bond formation is often considered as the rate-determining step. However, through mechanistic... 

Jamison s enantioselective coupling of imines with alkynes and organoboranes [11]... 

The couphng of N-substituted benzaldimines, mediated by the zinc-copper couple in the presence of (+)-camphorsulfonic acid (CSA) in DMF, was investigated. The best results were obtained for the imine 22, and the optimal balance of yield, diastereoselectivity and enantioselectivity for the diamine 23 was obtained using 3equiv of (+)-CSA [17] (Schemes). How-... 

Scheme 13 Enantioselective carbonyl (Z)-dienylation via reductive coupling of acetylene to aldehydes and imines mediated by hydrogen...

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

The diastereoselective addition to imines proceeds well with aromatic enolsi-lanes (249). Propiophenone- and tetralone-derived enolsilanes provide good levels of diastereoselectivity (>95 5) and excellent enantioselectivity (>98% ee) with selective formation of the anti diastereomer. Nonaromatic enolsilanes are somewhat less selective although cyclohexanone enolsilane still provides useful levels of diastereoselectivity and enantioselectivity (92 8 anti/syn and 88% ee at -78°C). A one-pot procedure using glyoxylate, sulfonamide, and enolsilane as coupling partners was developed subsequently, leading to the product in comparable yields and selectivities (250, 251). 

For enantioselective copper catalyzed addition of organozinc reagents to imines, see [97-116]. Enantioselective Ni-catalyzed alkyne, imine, triethylborane 3-component coupling has been reported, but modest selectivities (51-89% ee) are observed. For this method, vinylation is accompanied by ethyl transfer [149]... 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

In 1998, Yamamoto et al. reported the first catalytic enantioselective allylation of imines with allyltributylstannane in the presence of a chiral 7i-allylpalladium complex 23 (Scheme 9) [15]. The imines derived from aromatic aldehydes underwent the allylation with high ee values. Unfortunately, the allylation reaction of aliphatic imines resulted in modest enantioselectivities. They proposed that a bis-Jt-allylpalladium complex is a reactive intermediate for the allylation and reacts with imines as a nucleophile. The bis-Jt-allylpalladium complex seemed the most likely candidate for the Stille coupling [16]. Indeed, the Stille coupling reaction takes place in the presence of triphenylphosphine even if imines are present, whereas the allylation of imines occurs in the absence of the phosphine [17]. They suggested the phosphine ligand played a key role in controlling the... 

A related rhodium catalyzed enantioselective reductive coupling of acetylene to N arylsulfonyl imines leads to the formation of (Z) dienyl allylic amines (Scheme 1.28) [105]. The scope of the reaction is comparable to that demonstrated for the analogous iridium catalyzed process. The reaction between the acetylene and rhodium leads to the oxidative dimerization of acetylene to form a cationic rhoda cyclopentadiene that then reacts with the imine to generate the product after the protolytic cleavage and reductive elimination. 

Hydroxy-4-phenyl-P-lactams. The lithium enolate of (silyloxy)acetates (2) couple with the N-(trimethylsilyl)imine 3 to give 3-hydroxy-4-aryl- -lactams (4). The stereoselectivity depends in part on the size of the silyloxy group but mainly on the ester group. Use of either (+)- or (—)-/ra/w-2-phenyl-l-cyclohexyl (I) as the chiral auxiliary results entirely in a cw-/3-lactam (4) in 80% yield and 96-98% ee. Use of (-)-menthyl or of Oppolzer s D-isobornyl auxiliary (12,103-104) results in lower yields and enantioselectivity. The cyclocondensation with the ester 2 from (-)-l results in (3R,4S)-4 in 96% ee. On desilylation and acid hydrolysis, this lactam provides (2R,3S)-... 

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