Chiral imine reagents

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

During the past decade, the main focus of studies related to the well-known349 CeCl3- or SnCl2-catalyzed reactions of allylzinc and benzylzinc halides with imines was the application of polymer-supported chiral imines.350,351 An example of such reactions is shown in Scheme 135.350 It should be noted that attempts using arylzinc reagents in... 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

Based on the Kulinkovich reagent (Ti(OiPr)4/iPrMgCl), a new route to allyltita-niums has been devised by Sato and coworkers and this has allowed the synthesis of chiral allylTi reagents which, by reaction with aldehydes and imines provide diverse polyfunctional chiral building blocks. Thus, while a number of versatile and dependable Ti-based allyl-transfer reagents are now available, the development and employment of chiral allyltitaniums appears to be poised for new application. 

Scheme 9.27 Kinetic resolution of an allenylzinc reagent using a chiral imine.

In an attempt to prepare alkylamines by asymmetric reduction of imines with chiral hydride reagents, diphenylphosphinyl imines (38), prepared by reaction of ketoximes (39) with chlorodiphenylphosphine [(Cg 115)2 PCI], were reduced in the presence of a variety of chiral aluminum and boron hydride reagents43. Among the most promising reagents was BINAHL-H44 (40), a chiral hydride compound prepared by the modification of lithium... 

A new stereocenter is formed when a synthon 143 with umpoled carbonyl reactivity (d reactivity) is introduced into aldehydes or imines. The enantioselective variant of this type of reaction was a longstanding problem in asymmetric synthesis. The very large majority of a-hetero-snbstitnted carbanions which serve as eqnivalents for synthons like 142 and 143 lead to racemic products with aldehydes or imines. However, enantiomerically pnre acylions and a-hydroxy carboxylic acids or aldehydes (144 and ent-144, respectively) as well as a-amino acids and aldehydes (145 and ent-145) are accessible either by nsing chiral d reagents or by reacting the components in the presence of chiral additives (Scheme 18). 

It turned out that the requirements of such a chiral d reagent are fulfilled by the l-bromo-l-lithio-l-aUcenes S- and /f-41, which are available from the corresponding enantiomer of lactate . When added to aldehydes or imines, significant diastereose-lectivity will be displayed only by the fi-diastereomer 41. Thus, the selective exchange of the bromine atom in the Z-position of the dibromoaUcene 40, outlined in Scheme 9, is prerequisite to the efficiency of this concept. 

Oxidation of chiral sulfonimines (R"S02N=CHAr)and chiral sulfamyl-imines (R RNS02N=CHAr)affords optically active 2-sulfonyloxaziridines and 2-sulfamyloxaziridines, respectively. These chiral, oxidizing reagents have been used in the asymmetric oxidation of sulfides to sulfoxides (15-68% ee), 11-13 selenides to selenoxides (8-9% ee] enolates to a-hydroxycarbonyl compounds (8-37% ee) and in the asymmetric epoxidation of alkenes (15-40% ee)... 

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

Enantiomerically pure homoallylic amines are very important chiral building blocks for the synthesis of natural products. However, enantioselective methods for homoallylamine are quite undeveloped. In 1995, Itsuno and co-workers reported the first example of enantioselective allylation of an imine (Scheme 7) [13]. The reaction of N-trimethylsilylbenzaldimine 19 with a chiral allylboron reagent 20 in ether at -78 °C afforded the corresponding homoallylamine 22 in 73% ee. 

Hashimoto, Y. Takaoki, K. Sudo, A. Ogasa-wara, T. Saigo, K. Stereoselective addition reaction of organolithium reagents to chiral imines derived from erythro-2-amino-l,2-diphenylethanol. Chem. Lett. 1995, 235-236. 

Chiral imines have proved to be useful reagents in the synthesis of cyclic systems. For example, imines derived from (S)-( — )- and (R)-( + )-l-phenylethylamine 412 have been used in the preparation of optically pure polysubstituted cyclopentanone derivatives 414 (equation 87)252 and in enantioselective steroid synthesis (equation 88)253. 

Chiral Cuprate Reagents. This chiral amine has also found application in asymmetric conjugate addition of copper azaeno-lates to cyclic enones. Lithium azaenolates of optically active acetone imines have been used in the preparation of chiral cuprate reagents. However, the asymmetric induction is low (17-28% ee) when this amine is employed (eq 5). ... 

Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3 -diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14). Endo products are obtained with a high level of asymmetric induction (>90% ee) however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15). BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16). ... 

The first highly diastereoselective hydrophosphonylation of heterocyclic imines, 3-thiazolines (330) by a chiral phosphorus reagent BINOL, has been performed. The relative configuration of BINOL and the newly formed stereogenic centre in the a-amino phosphonic acid derivatives (331) have been elucidated by X-ray analysis. 

Homoallylic amines (Z-diastereomers) are formed from the appropriate imines in the presence of vinylcerium dichloride (Scheme 297). The CH2=CHCeCl2 reagent was prepared from CH2=CHMgBr and GcGI(. Using CH2=CHCeCl2 some chiral imines could also be transformed into /-products with high diastereoselectivity.1082... 

Scheme 3.12 illustrates the polymer-supported aUylboron reagents derived from chiral N-sulfonylamino alcohols and used for the asymmetric synthesis of homoal-lylic alcohols and amines (see Scheme 3.12) ]29]. All of these asymmetric allylbora-tions were performed using the polymeric chiral aUylboron reagent prepared from triallylborane and PS-supported N-sulfonylamino alcohols 38-41. High levels of enantioselectivity were obtained in the asymmetric allylboration of imines with the polymeric reagent derived from norephedrine.

The continued fascination chemists possess with asymmetric synthesis provides the basis for the next four procedures. The synthesis of (R)-(-)-10-METHYL-l(9)-OCTALONE-2 is a nice demonstration of an asymmetric Michael addition by a chiral imine followed by an aldol—in short an asymmetric Robinson annulation. The asymmetric glycolization to STILBENE DIOL (R,R-l,2-DIPHENYL-I,2-ETHANEDIOL) represents an olefin oxidation using catalytic alkaloids in tandem with osmium tetroxide. As reagents for a variety of asymmetric alkylations, the preparation of 2-CYANO-6-PHENYLOXAZOLOPIPERIDINK is pavscnicd as well as another route to... 

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