Chiral metal amides

Most successful approaches involving addition reactions in the presence of chiral additives utilize organolithium, organomagnesium and the recently introduced organotitanium reagents, which are known to coordinate with amines, ethers, metal amides and alkoxides. 

Before the emergence in the mid-1980s of the asymmetric deprotonation of cA-dimethyl cyclohexanone using enantiomerically pure lithium amide bases, few reports pertaining to the chemistry of these chiral reagents appeared. Although it is not the focus of this chapter, the optically active metal amide bases are still considered to be useful tools in organic synthesis. Readers are advised to consult the appropriate literature on the application of enantiomerically pure lithium amides in asymmetric synthesis.6... 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

More recently a-C-metallated amides of the chiral amine,... 

We turned our efforts to a synthesis in which a chiral 5-carbon unit would be coupled to a 6-carbon structure bearing functionality permitting resolution. The 5-carbon fragment would contain the hydrocarbon asymmetric center (C-8 of VII) the other unit would provide C-2. Commercially available (S>)-2-methyl 1-butanol was determined to be >99% pure. However, the R-alcohol (acid, aldehyde, etc.) would have to be synthesized. Asymmetric alkylations of chiral a-metallated amides were performed, but the enantiomeric excesses were not sufficiently high. In particular we noted that alkylations involving a short chain bifunctional compound (e.g., 3-methoxy-propyl iodide) provided slightly lower ee s than did the parent alkyl iodide. 

Asymmetric 1,3-dipolar cycloadditions of azomethine imines with terminal alkynes have been catalysed by 11 chiral ligand (8) coordinated metal amides to form N,N-bicyclic pyrazolidinone derivatives. Mechanistic studies have established the factors that determine the regioselectivity of the stepwise reaction. Novel phosphoramidite ligands (9) coordinated with palladium have been used to effect enantioselective synthesis of pyrrolidines by 3-P 2-cycloaddition of trimethylenemethane (from 2-trimethylsilylmethyl allyl acetate) to a wide range of imine acceptors (Scheme 11). ... 

The generalized application of the aminolysis of halophosphanes has been the method of choice for the preparation of a wide variety of chiral phosphinous amides by starting from enantioenriched primary amines [36]. The aminolysis reaction occurs efficiently even when the halophosphane is placed in the coordination sphere of a metal, as in the palladium and platinum complexes of the type ds-M(Ph2PCl2)2Cl (M=Pd, Pt) [37,38]. 

As shown in the previous two sections, rhodium(n) dimers are superior catalysts for metal carbene C-H insertion reactions. For nitrene C-H insertion reactions, many catalysts found to be effective for carbene transfer are also effective for these reactions. Particularly, Rh2(OAc)4 has demonstrated great effectiveness in the inter- and intramolecular nitrene C-H insertions. The exploration of enantioselective C-H amination using chiral rhodium catalysts has been reported by several groups.225,244,253-255 Hashimoto s dirhodium tetrakis[A-tetrachlorophthaloyl-(A)-/ r/-leuci-nate], Rh2(derived rhodium complex, Rh2(i -BNP)4 48,244 afforded moderate enantiomeric excess for amidation of benzylic C-H bonds with NsN=IPh. 

Striking examples of this phenomenon are presented for allyl and homoallyl alcohols in Eqs. (5) to (7). The stereodirection in Eq. (5) is improved by a chiral (+)-binap catalyst and decreased by using the antipodal catalyst [60]. In contrast, in Eq. (6) both antipode catalysts induced almost the same stereodirection, indicating that the effect of catalyst-control is negligible when compared with the directivity exerted by the substrate [59]. In Eq. (7), the sense of asymmetric induction was in-versed by using the antipode catalysts, where the directivity by chiral catalyst overrides the directivity of substrate [52]. In the case of chiral dehydroamino acids, where both double bond and amide coordinate to the metal, the effect of the stereogenic center of the substrate is negligibly small and diastereoface discrimination is unsuccessful with an achiral rhodium catalyst (see Table 21.1, entries 9 and 10) [9]. 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

As with the above pyrrolidine, proline-type chiral auxiliaries also show different behaviors toward zirconium or lithium enolate mediated aldol reactions. Evans found that lithium enolates derived from prolinol amides exhibit excellent diastereofacial selectivities in alkylation reactions (see Section 2.2.32), while the lithium enolates of proline amides are unsuccessful in aldol condensations. Effective chiral reagents were zirconium enolates, which can be obtained from the corresponding lithium enolates via metal exchange with Cp2ZrCl2. For example, excellent levels of asymmetric induction in the aldol process with synj anti selectivity of 96-98% and diastereofacial selectivity of 50-200 116a can be achieved in the Zr-enolate-mediated aldol reaction (see Scheme 3-10). 

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