Binol-zinc complex

Catalytic enantioselective epoxidation of 0, -ENONES WITH A BiNOL-ziNC-coMPLEx. 249... 

CATALYTIC ENANTIOSELECTIVE EPOXIDATION OF a, -ENONES WITH A BINOL-ZINC-COMPLEX... 

The hetero-DielsAlder reaction (hDA) using iminium species has been commonly used for the synthesis of reduced pyridines and pyridones . The aza-1,3-butadiene 107 was employed in hDA reaction to synthesize the key intermediate 108 in the total synthesis of the pyridine-based natural product piericidin (Scheme 60) <2005JA15704>. The reaction of Danishefskys diene with N-functionalized imine 109 in the presence of (A)-BINOL zinc complex has been utilized to produce 4-piperidones 110 in moderate to high enantioselectivity (Scheme 61) <2004SL711>. 

Shibasaki and colleagues achieved further efficient catalysis using a zinc complex as a catalyst [5,14], which was prepared from Et2Zn and linked-BINOL... 

A library of chiral zinc complexes formed in situ by the combination of achiral and racemic diimines with 3,30-di(3,5-ditrifluoromethylphenyl)-BINOL and diethylzinc have been evaluated in the asymmetric addition of diethylzinc to V-acylimines.126 High enantioselectivities of up to 97% ee and yields of up to 96% have been achieved for a wide range of aromatic imines in dichloromethane at -30 °C. 

The use of the zinc complex of the BINOL ligand 946 in the hDA reaction between Danishefsky s diene 947 and aldehydes proceeds in excellent yield and enantioselectivity to afford dihydropyran-4-ones 948 (Equation 370, Table 45) <2002OL4349>. An asymmetric diethyl zinc addition can occur in tandem with the cycloaddition reaction between Danishefsky s diene 947 and isophthalaldehyde using a related catalyst 949 (Equation 371) <20030L1091, 2005T9465>. 

Upon reaction with iodoacetate 312, a-carbonyl radical 319 is generated under release of methyl iodide. Treatment of BINOL-type ligand 315 with diethyl zinc will produce dinuclear zinc complex 320 upon deprotonation of both phenolic groups in the ligand. The reaction of complex 320 with radical 319 opens a second catalytic cycle B that leads to the Reformatsky reagent 321, which is assumed to be a C-bound zinc enolate wherein the metal keeps its coordination to the bidentate ligand - an obvious prerequisite to provide enantioselectivity in the final step that closed cycle B the addition to the aldehyde that leads to zinc aldolate 322 under concomitant regeneration of the dinuclear complex 320. 

In the approaches toward a direct asymmetric Mannich reaction by enolate formation with the metal of the catalyst also, the well-proved systems of the analogous aldol reactions were widely applied. Here, it is referred to some of these protocols wherein a metal enolate is involved, as least as assumed and plausible intermediate [183]. Shibasaki and coworkers used a dinuclear zinc complex derived from linked BINOL ligand 371 for catalyst in direct Mannich reactions of a-hydroxy ketones 370 with Af-diphenylphosphinoyl imines 369 to give ti-configured a-hydroxy-P-amino ketones 372 in high yield, diastereoselectivity, and enantioselectivity (Scheme 5.97) [184]. The authors postulate the metal to form a chelated zinc enolate by double deprotonation of the a-hydroxy ketone. This enolate approaches with its Si-face to the Si-face of the imine, as illustrated by the transition state model 373, in agreement with the observed stereochemical outcome. It is remarkable that opposite simple diastereoselectivity arises from the Mannich reaction (anti-selective) and the previously reported syn-selective aldol reaction [185], although the zinc enolates... 

Scheme 5.97 Sibasaki s Mannich procedure based on zinc complexes of "linked BINOL" 371.

Since these early reports, several groups have continued to improve these catalytic reactions. The most successful catalysts to date are rare earth/alkali metal/BINOL complexes like LLB, while htanium, aluminum, and zinc catalysts have also been described. 

A zinc-bis(BINOL) complex has been employed to effect chemoselective enolate formation from an a-hydroxy ketone (in the presence of an isomerizable imine) to give a Mannich-type product in high ee 1... 

Asymmetric catalysis of ene reactions was initially investigated for the intramolecular examples, because intramolecular versions are much more facile than their inter-molecular counterparts. The first reported example of an enantioselective 6-(3,4) car-bonyl-ene cyclization employed a BINOL-derived zinc reagent [81]. This, however, was successful only when excess zinc reagent (at least 3 equiv.) was used. An enantioselective 6-(3,4) olefin-ene cyclization has also been developed which uses a stoichiometric amount of a TADDOL-derived chiral titanimn complex (Sch. 26) [82]. In this ene reaction, a hetero Diels-Alder product was also obtained, the periselectivity depending critically on the solvent system employed. In both cases, geminal disubstitution is required of high ee are to be obtained. Neither reaction, however, constitutes an example of a truly catalytic asymmetric ene cyclization. 

Oguni has reported asymmetric amplification [12] ((-i-)-NLE) in an asymmetric carbonyl addition reaction of dialkylzinc reagents catalyzed by chiral ami-noalcohols such as l-piperidino-3,3-dimethyl-2-butanol (PDB) (Eq. (7.1)) [13]. Noyori et al. have reported a highly efficient aminoalcohol catalyst, 2S)-3-exo-(dimethylamino)isobomeol (DAIB) [14] and a beautiful investigation of asymmetric amplification in view of the stability and lower catalytic activity of the het-ero-chiral dimer of the zinc aminoalcohol catalyst than the homo-chiral dimer (Fig. 7-5). We have reported a positive non-linear effect in a carbonyl-ene reaction [15] with glyoxylate catalyzed by binaphthol (binol)-derived chiral titanium complex (Eq. (7.2)) [10]. Bolm has also reported (-i-)-NLE in the 1,4-addition reaction of dialkylzinc by the catalysis of nickel complex with pyridyl alcohols [16]. 

Other use of the functionalized chiral BINOL includes the 5,5, 6,6, 7, 7, 8,8 -octahydro derivative developed by Chan and coworkers, the titanium complex of which is more effective than BINOL in the enantioselective addition of triethylaluminum and diethylzinc a 4,4, 6,6 -tetrakis(perfluorooctyl) BINOL ligand developed for easy separation of the product and catalyst using fluorous solvents for the same zinc reaction an aluminum complex of 6,6 -disubstituted-2,2 -biphenyldiols used by Harada and coworkers in the asymmetric Diels-Alder reaction a titanium complex of (5 )-5,5, 6,6, 7,7, 8,8 -octafluoro BINOL employed by Yudin and coworkers in the diethylzinc addition, in the presence of which the reaction of the enantiomeric (/f)-BINOL is promoted . 

ZnX2," " ZnCl2," ° Zn(0Tf)2-H20," ZnF2 with diamine complex,- Et2Zn with (S, S) linked BINOL,dinuclear zinc catalyst," chiral zirconium catalyst" (e.g., Zr(0-... 

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