Metal nucleophile addition

Entry Metal Nucleophile Additive Conversion (%) Yieid (%) ... 

The synthetic methodology is not limited to diphosphines and could easily be extended to the asymmetric synthesis of triphosphine ligands such as 1,1,2-tris (diphenylphosphino)ethane (Scheme 3) [44]. Although the free triphosphine itself is not chiral in this instance, a chiral center is generated once it is chelated to a metal. Nucleophilic addition of diphenylphosphine to the metal template activated l,l-bis(diphenylphosphino)ethane proceeds smoothly to give a (solvent independent) equilibrium mixture of four diastereomeric products in an equilibrium ratio of... 

Many other reactions of ethylene oxide are only of laboratory significance. These iaclude nucleophilic additions of amides, alkaU metal organic compounds, and pyridinyl alcohols (93), and electrophilic reactions with orthoformates, acetals, titanium tetrachloride, sulfenyl chlorides, halo-silanes, and dinitrogen tetroxide (94). 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

With a-alkyl-substituted chiral carbonyl compounds bearing an alkoxy group in the -position, the diastereoselectivity of nucleophilic addition reactions is influenced not only by steric factors, which can be described by the models of Cram and Felkin (see Section 1.3.1.1.), but also by a possible coordination of the nucleophile counterion with the /J-oxygen atom. Thus, coordination of the metal cation with the carbonyl oxygen and the /J-alkoxy substituent leads to a chelated transition state 1 which implies attack of the nucleophile from the least hindered side, opposite to the pseudoequatorial substituent R1. Therefore, the anb-diastereomer 2 should be formed in excess. With respect to the stereogenic center in the a-position, the predominant formation of the anft-diastereomer means that anti-Cram selectivity has occurred. 

The high diastereoselectivity which is found in the nucleophilic addition of Grignard reagents to chiral 2-0x0 acetals can be explained by a chelation-controlled mechanism. Thus, coordination of the magnesium metal with the carbonyl oxygen and the acetal moiety leads to a rigid structure 3A in the transition state with preferred attack of the nucleophile occurring from the S/-side. 

Generally, in the nucleophilic addition to carbonyl groups, either magnesium compounds or alkali metal compounds (such as the Li, Na and K derivatives) are used. In some cases even potassium carbonate or piperidine were used as the base for condensation with sulfones. Good results were obtained when concentrated aqueous NaOH was used under phase-transfer conditions288,297,333. 

We shall discuss first reactions in which hydrogen or a metallic ion (or in one case phosphorus or sulfur) adds to the hetero atom, and then reactions in which carbon adds to the hetero atom. Within each group, the reactions are classified by the nature of the nucleophile. Additions to isocyanides, which are different in character, are treated at the end. 

The aza-Henry reaction is the nucleophilic addition of nitroalkanes to imines to give nitroamine derivatives. This reaction was also studied with metal-based catalysts [164]. 

Among all the nucleophilic addition reactions of carbonyl compounds, allylation reaction has been the most successful, partly due to the relatively high reactivity of allyl halides. Various metals have been found to be effective in mediating such a reaction (Scheme 8.4). Among them, indium has emerged as the most popular metal for such a reaction. 

The catalytic role of a Ni(0) species in this reaction may be attributed to oxidative addition of a Ni(0) species to isoprene in conjunction with protonation (leading to 33) or nucleophilic addition to benzaldehyde (leading to 35). Reduction of Ni(II) to Ni(0) by In(I) and metal exchange may form an... 

The selectivity of RNH2 on M/A1203 and Raney catalysts decreased in the order Co Ni Ru>Rh>Pd>Pt. This order corresponds to the opposite sequence of reducibility of metal-oxides [8] and standard reduction potentials of metalions [9], The difference between Group VIII metals in selectivity to amines can probably been explained by the difference in the electronic properties of d-bands of metals [3], It is interacting to note that the formation of secondary amine, i.e. the nucleophilic addition of primary amine on the intermediate imine can also take place on the Group VIII metal itself. Therefore, the properties of the metal d-band could affect the reactivity of the imine and its interaction with the amine. One could expect that an electron enrichment of the metal d-band will decrease the electron donation from the unsaturated -C=NH system, and the nucleophilic attack at the C atom by the amine [3], Correlation between selectivity of metals in nitrile hydrogenation and their electronic properties will be published elsewhere. 

Self-consistent field molecular orbital calculations by Fenske and coworkers have confirmed that nucleophilic additions to Fischer and related complexes [e.g., (CO)sCr=CXY, (T)5-C5H5)(CO)2Mn=CXY], are frontier orbital-controlled rather than charge-controlled reactions (7-9). Interaction of the HOMO of the nucleophile with the carbene complex LUMO (localized on Ca) destroys the metal-carbon w-interaction and converts the bond to a single one. 

The effect of metal basicity on the mode of reactivity of the metal-carbon bond in carbene complexes toward electrophilic and nucleophilic reagents was emphasized in Section II above. Reactivity studies of alkylidene ligands in d8 and d6 Ru, Os, and Ir complexes reinforce the notion that electrophilic additions to electron-rich compounds and nucleophilic additions to electron-deficient compounds are the expected patterns. Notable exceptions include addition of CO and CNR to the osmium methylene complex 47. These latter reactions can be interpreted in terms of non-innocent participation of the nitrosyl ligand. 

In contrast to the highly reactive organoboranes, borabenzene metal complexes are surprisingly inert toward nucleophiles. However, cationic complexes may undergo nucleophilic addition reactions, and nucleophilic substitution has been observed with compounds having a hydrogen or an electronegative substituent at boron. 

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