Asymmetric nucleophilic

Asymmetric nucleophilic addition of dialkylzinc to 3,4-dihydroisoquinoline 1-oxides 98YGK11. 

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Helquist et al. [129] have reported molecular mechanics calculations to predict the suitability of a number of chiral-substituted phenanthrolines and their corresponding palladium-complexes for use in asymmetric nucleophilic substitutions of allylic acetates. Good correlation was obtained with experimental results, the highest levels of asymmetric induction being predicted and obtained with a readily available 2-(2-bornyl)-phenanthroline ligand (90 in Scheme 50). Kocovsky et al. [130] prepared a series of chiral bipyridines, also derived from monoterpene (namely pinocarvone or myrtenal). They synthesized and characterized corresponding Mo complexes, which were found to be moderately enantioselective in allylic substitution (up to 22%). 

Asymmetric nucleophilic allylic substitution has rarely been studied in its heterogeneous version, probably because of the difficulties encoimtered in properly stabilizing and recycling Pd(0) species. Nevertheless, some promising examples have been pubhshed. Lemaire et al. [143] studied the activity and enantioselectivity of various chiral C2-diamines for the asymmetric Pd-catalyzed transformation of various allyl acetates. The structures tested are represented in Scheme 58. 

The novel asymmetric nucleophilic substitution to the ketimine was discovered and optimized for this preparation. 

The ANM group was selected as the nitrogen protecting group for the novel asymmetric nucleophilic substitution providing the optimum enantioselectivity. 

Thus, we discovered the first asymmetric nucleophilic addition of acetylides to kehmines. The reaction mechanism was unfortunately not clear during this study but we felt that aggregation of lithium species might play an important role. 

Asymmetric nucleophilic addition of Jt-allyl molybdenum complex as the final route. 

We will discuss each topic below. Later, we will discuss the key reaction, asymmetric nucleophilic addition of a n-allyl Mo complex, in great detail. 

Asymmetric Nucleophilic Addition of a ir-Allyl Mo Complex route... 

A newly developed asymmetric nucleophilic addition of malonate to 7i-allyl Mo complex was the cornerstone for this preparative campaign. 

When we used asymmetric nucleophilic addition of malonate to the Mo tt-allyl complex in our first delivery, the Mo chemistry was not so clearly understood, and our application would be the first large scale example, to the best of our knowledge. Initially our contributions to Mo chemistry were two-fold (i) replacement of non-commercially available (EtCN)3Mo(CO)3 or (C7H8)Mo(CO)3 by more stable and inexpensive Mo(CO)6 by incorporation of proper pre-activating time (ii) simplified preparation of the chiral ligand. Even after we completed the project, we still had a strong interest in Mo chemistry. 

Porco s synthesis of ( )-kinamycin C (3) constituted the first reported route to any of the diazofluorene antitumor antibiotics. This synthesis invokes several powerful transformations, including a modified Baylis-Hillman reaction, a catalyst-controlled asymmetric nucleophilic epoxidation, and a regioselective epoxide opening to establish the D-ring of the kinamycins. The tetracyclic skeleton was constructed by an... 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

The synthesis of the spiroisoxazoline natural product (+ )-calafianin 447 has been reported, using asymmetric nucleophilic epoxidation and nitrile oxide cycloaddition as key steps. Syntheses and spectral analyses of all calafianin stereoisomers lead to unambiguous assignments of relative and absolute stereochemistry (494). 

The asymmetric alkylation of a carbonyl group is one of the most commonly used chirality transfer reactions. The chirality of a substrate can be transferred to the newly formed asymmetric carbon atom through this process. In surveying chiral enolate systems as a class of nucleophile, three general subdivisions can be made in such asymmetric nucleophilic addition reactions intra-annular, extra-annular, and chelation enforced intra-annular. 

CHIRAL CATALYST-INDUCED ALDEHYDE ALKYLATION ASYMMETRIC NUCLEOPHILIC ADDITION... 

MgBr2-mediated asymmetric nucleophilic addition of Grignard reagents and allyl-tributyltin to aldehydes bearing sugar-derived jS- or y-tetrahydropyranyloxy chiral auxiliaries designed to complex with MgBt2 has been achieved. ... 

Adolfsson, H. Mobrg, C. (1995) Chiral Lewis acid catalyzed asymmetric nucleophilic ring opening of cyclohexene oxide., Tetrahedron Asymmetry, 6 2023-2031. 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

Asymmetric Syntheses with Lithiated a-Aminonitriles 1.1.4.1 Asymmetric Nucleophilic a-Aminoacylation... 

In continuation of our investigations on asymmetric nucleophilic acylations with lithiated a-aminonitriles [40], we envisaged the asymmetric synthesis of 3-substituted 5-amino-4-oxo esters A, bearing both a-amino ketone and 5-amino ester functionalities (Scheme 1.1.14) [41]. Since a-amino ketones are precursors of chiral p-amino alcohols [42, 43] and chiral amines [43], their asymmetric synthesis has the potential to provide valuable intermediates for the synthesis of biologically active compounds, including peptidomimetics [44]. The retrosynthetic analysis of A leads to the a-aminoacyl carbanion B and p-ester carbocation... 

Scheme 1.1.14 Retrosynthetic strategy for the asymmetric nucleophilic a-aminoacylation.

Asymmetric epoxidation of a prochiral alkene is an appealing process because two stereogenic centers are established in the course of the reaction. Often, the starting alkene is inexpensive. There have been several interesting recent advances in the asymmetric nucleophilic epoxidation. 

These early results paved the way for a myriad of applications of this process in organic synthesis, as described in detail in this chapter. It should be pointed out that only additions of stabilized nucleophiles are included here, with the addition of reactive nucleophiles (organolithiums, Grignards, cuprates, etc.), Lewis acid promoted additions and asymmetric nucleophilic additions, among others, being covered in Chapters 1.3 and 1.5, respectively, in this volume. 

Asymmetric Nucleophilic Addition to Electron Deficient Alkenes... 

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