Chirogenic reaction

Chirogenic reactions, i.e. reactions which lead from achiral starting materials to chiral products... 

The Heck reaction in its original form is not a chirogenic reaction. However, the situation changes if cyclic alkenes are employed as a coupling component, as was initially shown by Larock et al. [6]. In such cases, non-conjugated, chiral products of type 6 are formed because only one syn-Y atom is available for f-W elimination in the intermediates of type 7 (Scheme 3). While racemic mixtures are obtained with achiral catalysts, such transformations of course afford the possibility of achieving enantioselective Heck reactions. 

See [41] for the meaning of the term chirogenic reaction step and the usefulness of its application. 

A chirogenic reaction step, as defined by A. Eschenmoser [92] is one in which a chiral product is formed from an achiral starting material, any necessary reagent being also achiral. See [91a] on catalyses that resulted in only moderate enantiomeric excesses. 

How might the chirogenic ) reaction between 139 and a dienophile of type 140 be steered in the desired direction by molecular reaction mediators Is there any kind of general procedure for systematically searching for such mediating agents The answer is YES, provided that the search is carried out in hierarchically structured testing steps. 

The Pd(II)-induced intramolecular attack of heteroatom nucleophiles to alkenes or alkynes with subsequent carbonylation leads to acylpaUadium intermediates, which in turn can further react to carboxylic acid derivatives. This chemistry opens highly efhcient tandem transformations, which are of outstanding value for the synthesis of complex heterocyclic molecules. While the chemo- and regioselectivities of such reactions can be efficiently controlled in many cases by proper choice of substrates and reaction conditions, the control of the absolute configuration in the case of chirogenic reactions stiU remains a challenge for future research and development. 

The black arrow on red ground in Fig. 14 denotes a chirogenic reaction step, by which two achiral educt components are transformed into a chiral product. A. Eschenmoser [26] has coined that term, to emphasize that those specially designated reaction steps carry the opportunity for enantioselective generation of molecular chirality through catalysis . 

By the use of TiCl2(OiPr)2 in the presence of appropriately substituted TAD-DOLs [32] Af. Bauch [33] effected the enantioselective version of the chirogenic reaction step of Fig. 24. 

Cr6py KVL, Imamoto T (2003) New P-Chirogenic Phosphine Ligands and Their Use in Catalytic Asymmetric Reactions. 229 1-40 Cristau H-J, see Taillefer M (2003) 229 41-73... 

New P-Chirogenic Phosphine Ligands and their Use in Catalytic Asymmetric Reactions... 

Scheme 1. First use of P-chirogenic phosphine ligands in asymmetric hydrogenation reaction...

On the basis of the conclusions accumulated over the years, novel highly efficient P-chirogenic phosphines were designed, synthesized, and tested in a variety of enantioselective reactions. These issues will be stressed in the following paragraphs. 

P-Chirogenic phosphine/sulfide hybrid phosphine-boranes 80 were synthesized from the reaction between (l )-tosylates 79 [94] and sodium thiolate in DMF at ambient temperature as depicted in Scheme 12, or alternatively by a one pot synthesis consisting of the nucleophilic attack of the chirally induced hthium salt of 74 on phenyl disulfide. Both methodologies provided the desired sul-fide/phosphine boranes in excellent yields [10]. 

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

Pd-catalyzed asymmetric allylic alkylation is a typical catalytic carbon-carbon bond forming reaction [ 126 -128]. The Pd-complex of the ligand (R)-3b bearing methyl, 2-biphenyl and cyclohexyl groups as the three substituents attached to the P-chirogenic phosphorus atom was found to be in situ an efficient catalyst in the asymmetric allylic alkylation of l-acetoxy-l,3-diphenylprop-2-en (4) with malonate derivatives in the presence of AT,0-bis(trimethylsilyl)acetamide (BSA) and potassium acetate, affording enantioselectivity up to 96% and quantitative... 

In 2001, Imamoto et al. reported the preparation of novel chiral S/P-bidentate ligands containing a chirogenic centre at the phosphorus atom and their stereoinduction capability in palladium-catalysed asymmetric allylic substitution reactions (Scheme 1.14)." ... 

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