Chiral nucleophiles

SCHEME 8.18 Arylation of Schollkopf s bislactim ether 75 with aryne 77. 

SCHEME 8.19 Synthesis of (R)-4-nitroaryIprolines 87 by oxidative nucleophilic substitution of hydrogen 

Good to excellent diastereoselectivities are also obtained with chiral enolates derived from menthol ester 88 [69], Schiffbase of 2-hydroxypinan-3-one 89 [70], bicyclic lactam 90 [71], 2-phenyloxazoline 91 [72], (25,55)-cw-l,3-dioxolan-4-one 92 [73], and imidazolidinone 93 [74, 75] (Fig. 8.4) 

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Organolithium Reagents/Sparteine Combinations as Chiral Nucleophiles for Enantioselective Additions... 

Extending the same concept of a planar chiral nucleophilic or basic heterocyclic Fe-sandwich complex, aza-ferrocenes 65 were prepared. The latter have also been successfully applied as bidentate ligands in transition metal catalysis [85]. 

Hodous BL, Fu GC (2002) Enantioselective Staudinger synthesis of P-lactams catalyzed by a planar-chiral nucleophile. J Am Chem Soc 124 1578-1579... 

Experimentally, a chiral nucleophile was prepared by reaction of n-BuLi (or n-HexLi) with a mixture of chiral modifier 46 and cyclopropylacetylene 37 at -10 to... 

The chiral nucleophiles CgHi3C H(Me)X (X = Br, 0S02Me) alkylate the benzophenone metal ketyl at one of the rings as well as at the carbonyl carbon atom. Both pathways lead to the corresponding products in approximately equal amounts (Hebert et al. 1983 Scheme 6.10). 

In the context of our work in the area of chiral nucleophilic carbenes and their utility in organic synthesis, we have developed a conceptually distinct approach to catalyzed acylation using a-haloaldehydes as acylation precursors. The use of a chiral triazolium salt in the presence of base allows an enantioselective desymme-trization of meio-hydrobenzoin to proceed in 83% ee and good yield ... 

This review will focus on the use of chiral nucleophilic A-heterocyclic carbenes, commonly termed NHCs, as catalysts in organic transformations. Although other examples are known, by far the most common NHCs are thiazolylidene, imida-zolinylidene, imidazolylidene and triazolylidene, I-IV. Rather than simply presenting a laundry list of results, the focus of the current review will be to summarize and place in context the key advances made, with particular attention paid to recent and conceptual breakthroughs. These aspects, by definition, will include a heavy emphasis on mechanism. In a number of instances, the asymmetric version of the reaction has yet to be reported in those cases, we include the state-of-the-art in order to further illustrate the broad utility and reactivity of nucleophilic carbenes. 

The mechanism by which chiral nucleophiles catalyze asymmetric acyl transfer in the KR of, yec-alcohols can be seen as a three-step process (Scheme 1) [2]. 

It should be noted that asymmetric acyl transfer can also be catalyzed by chiral nucleophilic A-heterocyclic carbenes [27-32] and by certain chiral Lewis acid complexes [33-37] but these methods are outside the scope of this review. Additionally, although Type I and Type II tr-face selective acyl transfer processes have been reported to be catalyzed by some of the catalysts described in this review, these also lie outside the scope of this review. 

By contrast, the use of phosphines as catalysts is a more recent phenomenon and the development of chiral phosphines has been less well explored, possibly also because of synthetic difficulties associated with developing chiral nucleophilic phosphorus-containing scaffolds. 

Very recently, Ishirihara et al. [237] reported the application of a chiral iodine atom throngh the reaction of NSI and a chiral nucleophilic phosphoramidite for the halocyclization of homo(polyprenyl)arenes. 

Enhanced reactivity as well as high endo-selectivity based on the rigid transition structure of N-metalated azomethine ylides is attractive for asymmetric 1,3-dipolar cycloaddition reactions. There are several reports known for the design of effective chiral nucleophiles in asymmetric cycloadditions. 

Besides the interesting possibility of connecting a chiral electrophile to a chiral nucleophile, which is created from the same precursor in a completely stereoselective manner, this sequence seems to open a general route to enantiomerically pure ot-Iithiated ethers29,32. 

D.l.l. Formation of C—C Bonds by Alkylation Reactions D.l.l.l. Alkylation of Chiral Nucleophiles... 

The chiral auxiliaries H-A developed by Evans et al. 176) were derivatives of naturally occurring amino acids. The (S)-proline-derived amide enolates (164) as well as the (S)-valine-derived amide enolates (166) and imide enolates (165) have proven to be exceptionally versatile chiral nucleophiles. 

One can also compare faces of a molecule in the same way as groups, since the comparison actually applies to environments. Thus, the two faces of the carbonyl groups of aldehydes, unsymmetrical ketones, esters, and other acid derivatives are enantiotopic. Reaction at the two faces by a chiral nucleophile will take place at different rates, resulting in asymmetric induction. 

Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

The introduction of a chiral auxiliary on the nitrogen of an azaenolate offers the capability to perform asymmetric conjugate additions of chiral nucleophiles to achiral acceptors. This is in contrast to the typical asymmetric conjugate addition of achiral nucleophiles to chiral acceptors.137 For example, the con-... 

Reactions of symmetrical dienyliron complexes with chiral nucleophiles 689... 

The first method, resolution, is unattractive unless both enantiomers are useful in synthesis. In some cases, such as the resolution of dienecarboxylic acid derivatives mentioned earlier (via the phenylethyl-ammonium salt), the resolution is efficient and provides optically pure materials in good yield.39 60,63 In certain cases, the dienyliron complex can be treated with a chiral nucleophile to give a mixture of dia-stereomers which are separated and then reconverted to enantiomerically pure dienyl complex.64 An example of this method is the resolution of complex (27 Scheme 33), via the menthyl ethers (195) and... 

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