Chiral auxiliaries overview

Overview. To solve these problems, we present the first example of a crystallization-induced asymmetric transformation using optically pure (R)-phenylglycine amide 1 as a chiral auxiliary. The (R,S)-3 diastereomer precipitates out of solution in 76-93% yield with a diastereomeric ratio (dr) > 99/1. (106 words)... 

Chiral Boronate Derivatives. A large number of chiral auxiliary reagents based on allylic boronates has been reported. This section provides a brief overview of the historically important ones, but it focuses mainly on the most popular systems and the emerging ones (Fig. 4). 

Asymmetric Mannich reactions provide useful routes for the synthesis of optically active p-amino ketones or esters, which are versatile chiral building blocks for the preparation of many nitrogen-containing biologically important compounds [1-6]. While several diastereoselective Mannich reactions with chiral auxiliaries have been reported, very little is known about enantioselective versions. In 1991, Corey et al. reported the first example of the enantioselective synthesis of p-amino acid esters using chiral boron enolates [7]. Yamamoto et al. disclosed enantioselective reactions of imines with ketene silyl acetals using a Bronsted acid-assisted chiral Lewis acid [8]. In all cases, however, stoichiometric amounts of chiral sources were needed. Asymmetric Mannich reactions using small amounts of chiral sources were not reported before 1997. This chapter presents an overview of catalytic asymmetric Mannich reactions. 

Fig.24 Overview of the synthesis and resolution of solution stable, chiral tetrahedron 6 [119]. a Formation of racemic, homochiral (AAAA)-6 and (AAAA)-6 b Chiral resolution and separation upon addition of s-nic ions (38) by formation of diastereomeric ion-pair (AAAA)-6-38 c Ion-exchange of chiral auxiliary 38 by achiral counterions such as NMe4+ and NEt4+ maintains the chirality of the resolved tetrahedra (AA AA)-6...

The goal of this 2nd edition of the Compendium of Chiral Auxiliary Applications remains to provide a wide-ranging overview of applications. However, the sheer size of the current data set dictated the need for an additional degree of refinement. The 1st edition nonselectively incorporated about 13,000 reaction entries and spanned more than 1200 pages. Now with more than 30,000 entries, this approach is no longer practical. 

This overview on the use of metal enolates for catalytic asymmetric aldol reaction may give an impression of the enormous progress in the development made mainly in recent years. Looking back on the aldol addition with chiral auxiliaries and comparing both concepts for this particular valuable reaction, one gets aware that in terms of enantioselectivity and particular simple diastereoselection (i.e., the control of syn- and h -configuration), the excellent traditional auxiliary approaches remain mostly unsurpassed. 

The asymmetric addition of organoaluminum to carbonyl compounds has been accomplished by using substrates involving chiral auxiliaries. In this section, recent examples published in this decade (to mid-2011) are overviewed. 

The immense number of chiral auxiharies in enolate chemistry and the large multitude of individual protocols based thereupon have been reviewed comprehensively over the years. In this context, the Houben-Weyl volumes on Stereoselective Synthesis deserve to be mentioned in particular because they provide an overview, complete at the time where the auxihary strategy was already well devel-oped. Therefore, this chapter does not intend to present a complete collection of auxiliaries in enolates. Instead, it will attempt to highhght those procedures that proved their rehabUity in apphcations in natural products and drug syntheses. Nevertheless, reference will be given to more recent alterations and improvements of those auxiharies that meanwhile became Classics in Stereoselective Synthesis [3]. 

From this short overview it appears that the majority of the recent studies on enantioselective cycloisomerizations have been focused so far on asymmetric Alder-ene type cyclizations with Pd and Rh catalysts, since these reactions represent an economical access into synthetically usefiil cyclopentene and cyclohexene frameworks (Sects. 10.2.1 and 10.3.1). For these processes, efficient chiral catalysts have been afforded mainly by atropisomeric diphosphines, but also DuPHOS, Skewphos and phosphine-oxazolines can occasionally represent suitable auxiliaries. 

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