Norephedrine, derivatives ligands

In other diethylzinc studies, a neural network modelling approach has been used to predict the utility of new enantioselective catalysts,222 norephedrine-derived ligands with three stereogenic centres catalyse enantioselective addition to aldehydes and to chalcones,223 and a chiral sulfonamide ligand based on tartaric acid gives good ees in addition to both aldehydes and ketones.224... 

Scheme 3.5 Norephedrine-derived amino thioacetate and thiocyanate ligands for additions of ZnEt2 to aldehydes.

Scheme 3.18 Norephedrine-derived thiophosphoramidate ligand for Ti-catalysed additions of ZnR2 to aldehydes.

The scope of this methodology was extended to the enantioselective cyclo-propylation of various aldehydes using dicyclopropylzinc in the presence of this norephedrine-derived thiophosphoramidate ligand combined with Ti(Oi-Pr)4 to achieve the corresponding cyclopropyl alkanols with enantioselectivities of up to 97% ee (Scheme 3.19). ... 

K. Evetraere, J.-F. Carpentier, A. Morteux, and M. Bulliard, N-Benzoyl-norephedrine derivatives as new, effident ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones, Tetrahedron Asymm. 1999, 10, 4083 4086. 

A few of these ligands are illustrated, including the camphor-derived ligand (6.03) (which was the first one to give high enantioselectivies), the norephedrine-derived aminoalcohol (6.04), the praline-derived ligand (6.05), aminoalcohols with axial chirality such as binaphthyl (6.06) and ferrocene-based aminoalcohols such as (6.07). ... 

Itsuno has described the first enantioselective allylation of aldehydes using crosslinked polymer-supported A-sulfonylated aminoalcohols as chiral ligands [146], Polymer-supported ligands 220 and 221 were prepared by copolymerisation of the norephedrine-derived monomer 218 or D-camphor-derived 219 with styrene and divinylbenzene (DVB) in a [chiral monomer]/[styrene]/[DVB] molar ratio of 1/8/1 (Scheme 90). 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

These reactions were also performed by Jin et al. in the presence of chiral amino thioaeetate ligands derived from (-i-)-norephedrine." As shown in Scheme 3.5, quantitative yields and excellent enantioselectivities of up to >99% ee were obtained in almost all eases of aldehydes, even when using 1.1 equivalent of ZnEt2 instead of 2 equivalents as usually employed. More recently, these authors developed eorresponding chiral amino thiocyanate derivatives from (-)-norephedrine and tested these new aprotic ligands for... 

Enantiopure amide derivatives (64) of -unsaturated a-hydroxy acids have been made by addition of a vinylsilane, R2R1C=(4ISiMe3, to /V-phcnylglyoxamide.181 The reaction is catalysed by scandium(III) triflate complexed to a C2-symmetric PYBOX ligand derived from (f )-norephedrine. 

Cyclic derivatives of 1,2- and 1,3-amino alcohols have been trialled as chiral catalysts in the addition of diethylzinc to benzaldehyde.229 Enantioselective addition of diethylzinc to benzaldehyde is the subject of other reports,230,231 including the use of triazinyl-BINOLs as enantioselective catalysts of addition to araldehydes, using Ti(IV) tetraisopropoxide.232 Two optically active amino thiocyanate derivatives (60) of (-)-norephedrine act as aprotic ligands for enantioselective addition of diethylzinc to aldehydes in up to 96% ee.233 The ee drops drastically if the -SCN group is changed to -SR. 

Optically active amino thiocyanate derivatives of (—)-norephedrine [e.g. (44)] have been found to act as effective aprotic ligands for enantioselective addition of diethylzinc to aldehydes.115 This reaction has provided optically active secondary alcohols with ee up to 96%. 

Optically active TV-sulfonylamino alcohols derived from D-camphor or norephedrine were found to be efficient chiral ligands for the enantioselective allylboration of iV-silylimines (Equation (170)) 646-648 B-Allyl(diisopinocampheyl)borane allylated iV-diisobutylaluminum imines with 87% ee (Equation (171)).649,650... 

Not only polystyrene supports, also other polymer supports were used in the preparation of polymeric amino alcohol ligands for dialkylzinc alkylation. For example, a vinylferrocene derivative with A,N -disubstituted norephedrine was copolymerized with vinylferrocene [60]. This polymeric chiral ligand (53) was used in the ethylation of aldehydes with moderate activity. Brown has reported that chiral oxazaborolidines have catalytic activity in the addition of diethyl zinc to aldehydes [61]. Polymers bearing chiral oxazaborolidines 37 were also active in the reaction and result on moderate enantioselectivity (<58 % ee) [62]. Enantiopure a,a -diphenyl-L-prolinol coupled to a copolymer prepared from 2-hydroxyethylmethacrylate and octadecyl methacrylate... 

The alkylation of 38 with menthyl chloroacetate produced a diastereomeric mixture of phosphine oxides 39 and 39. These mixtures could be separated into individual diastereomers in 10 1% yields by fractional recrystallisation in hexane. Each epimer was subjected to hydrolysis to the corresponding acid and subsequent decarboxylation to afford the optically pure methylphosphine oxides 40. Both transformations occurred in very high, often quantitative, yield. This method was an advance because, as seen before, the introduction of encumbered groups by the original Mislow method is cumbersome. Moreover, methylphosphine oxides 40 are key intermediates to prepare diphosphines of the DiPAMP family (see Scheme 2.11). The chemistry of Scheme 2.14 has been used much more recently by Hii and co-workers to prepare series of ami-nohydroxy phosphine oxide ligands by coupling the acid derived from 39 (R = t-Bu) with (-)-norephedrine and (S)-valinol. 

Another efficient method to prepare chiral propargylamines 42 using a multicomponent process is by alkylation of in situ formed propargyl imines from alkynals 40 and o-phenoxy aniline (11c) by dialkylzinc derivatives 41 in the presence of a chiral ligand, for instance a dipeptide, and a Lewis acid salt, as depicted in Scheme 11.16 [48], Furthermore, the synthesis of A-aryl propargyl amines can be also performed by the alkynylation using dimethylzinc and terminal acetylenes of several aldehydes and o-methoxyaniline catalyzed by (l/ ,25)-A-bis(p-methoxybenzyl)norephedrine and phenylacetylene (52-93%, 79-97% ee) [49],... 

Structural distortions of hexacoordinate alkyl (Me and Et) titanium complexes are amenable to analysis by extended Huckel calculations.29 Alkyl complexes are key intermediates in transformations of alkenes catalysed by titanium and other metals.some relevant material is in a review of the literature year 1983 on titanium l while crystallographic data for organometallic titanium complexes are analysed and classified.32 Derivatives of N-sulphonylated norephedrines are good ligands for chirally modified titanium methyl complexes. These species react enantioselectively with aromatic aldehydes.33... 

---