6,6’-dibromo-BINOL

Addition to imines. Effective synthesis of a-aminonitriles and of 3-amino acid derivatives from imines calls for the use of a Zr complex of 6,6 -dibromo-BINOL. Products containing an oxygen functionality at the a-position are similarly accessible, the diastereoselectivity of such a reaction can be controlled by choosing the proper a-alkoxy substituent in the nucleophiles. The TBSO substituent favors syn products whereas BnO derivatives give anti products selectively. 

In the presence of a Zr complex of (J )-6,6 -dibromo-BINOL, A -(2-hydroxyphenyl)-aldimines participate in asymmetric hetero-Diels-Alder reactions It is an improvement to the reactions involving stoichiometric chiral boron reagents. 

The catalyzed hydrocyanation of imines (Strecker reaction) has the option of employing a stable (salen)aluminum chloride or a Zr complex of 6,6 -dibromo-BINOL, with BujSnCN. It is important to derive the imines firom o-aminophenol for the present purpose. 

Mannich reaction. A complex derived from (r-BuOjaHf, imidazole and 6,6 -dibromo-BINOL is air-stable. It is capable of asymmetric induction in catalyzing the Mannich reaction (80-90% ee). ... 

Polymeric BINOL aluminum chloride. Prepared by Ni(0)-catalyzed cross- coupling of chiral 6,6 -dibromo-BINOL diacetate, hydrolysis, and treatment with EtjAlCl, the chiral catalyst is effective for the Mukaiyama aldol reaction. 

In 2009, Jurczak and co-workers reported a highly enantioselective AFC reaction of thiophenes with butyl glyoxylates catalyzed by 6,6 -dibromo-BINOL/Ti" complex 3 in toluene (Scheme 6.2). The reactions delivered a variety of hydroxyl(thiophene-2-yl)acetates 4 in good yields (76-98%) with high enantioselectivity (92-98% ee). This is the first example of the efficient AFC reaction of thiophenes with alkyl glyoxylates. 

For regioselective introduction of a chiral sidechain to C-2 of the indole nucleus the higher nucleophilicity of C-3 must be overcome. Employing the 4,7-dihydro derivatives the preferred reaction site is moved (to the active a-position of 4,5-disubstituted pyrroles), and asymmetric Michael reaction has been demonstrated with a chiral 3,3 -dibromo-BINOL as catalyst. ... 

Michael reaction. A complex derived from (r-BuOlaZr and chiral 3,3 -dibromo-BINOL induces the enantioselective conjugate addition of indole (at C-3) to enones. ... 

SCHEME 10.27 Enantioselective tandem Friedel-Crafts conjugate addition/asymmetric protonation catalyzed by (/J)-3,3-dibromo-BINOL SnCl complex. 

Metljylcoumarone has been prepared by the cyclization of ethyl a-phenoxyacetoacetate followed by hydrolysis and decarboxylation of the resulting ethyl 3-methylcoumarilate,3 4 by debromination and rearrangement of 3,4-dibromo-4-methyl-coumarin to 3-methylcoumarilic acid followed by decarboxylation,4-6 by cyclization of phenoxyacetone with concentrated sulfuric acid,6 and by treatment of 3-coumaranone with methyl-magnesium iodide followed by dehydration of the resulting car-binol.7... 

The Stacker reaction has been employed on an industrial scale for the synthesis of racemic a-amino acids, and asymmetric variants are known. However, most of the reported catalytic asymmetric Stacker-type reactions are indirect and utilize preformed imines, usually prepared from aromatic aldehydes [24]. A review highlights the most important developments in this area [25]. Kobayashi and coworkers [26] discovered an efficient and highly enantioselective direct catalytic asymmetric Stacker reaction of aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst prepared from 2 equivalents of Zr(Ot-Bu)4, 2 equivalents of (R)-6,6 -dibromo-1, l -bi-2-naphthol, (R)-6-Br-BINOL], 1 equivalent of (R)-3,3 -dibromo-l,l -bi-2-naphthol, [(R)-3-Br-BINOL, and 3 equivalents of N-methylimida-zole (Scheme 9.17). This protocol is effective for aromatic aldehydes as well as branched and unbranched aliphatic aldehydes. 

Heterobimetallic complexes 2 and 22 catalyze asymmetric Diels-Alder reactions of some dienophiles with cyclopentadiene [110]. Use of 6,6 -dibromo-substituted BINOL ligands led to significantly improved yield, endo.exo ratio, and enantioselectivity. 

Kobayashi has demonstrated that a chiral zirconium catalyst derived from 3,3 dibromo or 3,3 dichloro BINOL can catalyze the addition of substituted allyl stannanes to the imines derived from 2 hydroxyaniline and aryl or hetereoaryl substituted aldehydes (Scheme 1.25) [95]. The active catalyst is possibly generated by the bonding of the alcohol functionalities of the imine and of allylstarmane to the zirconium center. 

A screening of various BINOL structures showed that substitution at the 6-position has a positive influence in the enantioselectivity, and 6,6 -dibromo derivative was the best ligand, affording up to >97% enantiomeric excess for the aldol product. On the other hand, a substitution at the 3,3 -position has a negative effect. 

Chiral Oxygen Ligands. Among the oxygen donor ligands, the BINOL-type ones are predominant (68). The parent compound and its 3,3 -dibromo-substituted derivatives form efficient catalysts with titanium and zirconium (Fig. 8). Binaphthol-modified titanium(lV) compounds are efficient catalysts for ene reactions of glyoxylic esters and olefins. The replacement of isopropoxide of the titanium precursor, TiCl2(OiPr)2, is a crucial step in the formation of the catalytic species. 

Zirconium(rV) t-butoxide, Zr(OtBu)4 is a widely used component of various in situ catalysts. BINOL, its 3,3 -dibromo and 6,6 -dibromo derivatives, and TAD-DOL have been used as chiral ligands (138). These types of catalysts have been used for enantioselective Strecker reactions and Mannich-type reactions (139). 

An example of this was reported by Beller and colleagues [82] in the reaction of 2,2 -dihydroxybiphenyl with a dibromo-substituted Hg-BINOL derived phospho-rchloridite (Scheme 2.93). In this reaction, only minor amounts of the targeted symmetric biphenol-based diphosphite were formed. The main constituent of the product mixture was the asymmetric binaphthol bridged compound. The latter could be isolated in a yield of 70% by precipitation in Et20. 

In 2006, Schaus and co-workers reported the BINOL derivatives catalyzed asymmetric allylboration of ketones. 3,3 -dibromo substituted BINOL was found to be very effective catalyst for allylboration of a wide variety of ketone substrates... 

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