Nucleophilic stoichiometric control

Nucleophiles add to the face of the ligand opposite to that which bears the metal when reactions occur by a direct addition pathway and under kinetic control ([2]). This stereocontrol effect is very strong (100% diastereo-selective), so the planar chirality of the metal complex can dominate other stereodirecting influences. There are no conventional stoichiometric control systems that can match the generality, versatility and reliability of this metal-mediated strategy for asymmetric induction. In the case of stoichiometric-control methods, it is essential that the multiple use is made of the control group (otherwise... 

For the other broad category of reaction conditions, the reaction proceeds under conditions of thermodynamic control. This can result from several factors. Aldol condensations can be effected for many compounds using less than a stoichiometric amount of base. Under these conditions, the aldol reaction is reversible, and the product ratio will be determined by the relative stability of the various possible products. Conditions of thermodynamic control also permit equilibration among all the enolates of the nucleophile. The conditions that permit equilibration include higher reaction temperatures, protic solvents, and the use of less tightly coordinating cations. 

The extension of equilibrium measurements to normally reactive carbocations in solution followed two experimental developments. One was the stoichiometric generation of cations by flash photolysis or radiolysis under conditions that their subsequent reactions could be monitored by rapid recording spectroscopic techniques.3,4,18 20 The second was the identification of nucleophiles reacting with carbocations under diffusion control, which could be used as clocks for competing reactions in analogy with similar measurements of the lifetimes of radicals.21,22 The combination of rate constants for reactions of carbocations determined by these methods with rate constants for their formation in the reverse solvolytic (or other) reactions furnished the desired equilibrium constants. 

The intermolecular addition of nitrogen nucleophiles has been shown to lead to interesting products, with remarkable control based on the reaction conditions (Scheme 10). Carbonylation of the organo-Pd intermediate can also be efficient, leading to /3-amino esters. Unfortunately, these processes require stoichiometric Pd no reoxidation scheme has been developed. 

The nucleophilic addition on substituted ketenes is a well-known method to generate a prochiral enolate that can be further protonated by a chiral source of proton. Metallic nucleophiles are used under anhydrous conditions therefore, the optically pure source of proton must be added then (often in a stoichiometric amount) to control the protonation. In the case of a protic nucleophile, an alcohol, a thiol, or an amine, the chiral inductor is usually present at the beginning of the reaction since it also catalyzes the addition of the heteroatomic nucleophile before mediating the enantioselective protonation (Scheme 7.5). The use of a chiral tertiary amine as catalyst generates a zwitterionic intermediate B by nucleophilic addition on ketene A, followed by a rapid diastereoselective protonation of the enolate to acylammonium C, and then the release of the catalyst via its substitution by the nucleophile ends this reaction sequence. 

Iwasawa et al. have demonstrated that the endo-seleclive cycloalkenylation of co-acetylenic SEE is successfully achieved by stoichiometric or catalytic use of W(C0)5 THF (Scheme 10.101) [269]. In the reaction of SEE 99 fhe mode of cyclization endo or exo can be controlled by appropriate choice of the silyl group, the amount of W(CO)5, and the solvent. The W(CO)5-promoted cyclization would proceed by nucleophilic addition of fhe enolate to a W(CO)5-coordinated alkyne and/ or a vinylidene W(CO)5-complex. Quite recently, the cyclization of co-iodoacetylenic SEE such as 100 has been found to afford fhe iodine-migrated products in good yields [270]. This observation indicates the presence of the vinylidene complex intermediate 101. 

The feedstock supply is limited by the volume available from the paper industry. Introduction of chlorine into a molecule means that great care must be taken to remove it all and stringent controls put in place to ensure that the techniques employed for its total removal (below ppb levels) are effective. The use of sodium acetate as a nucleophile to displace chlorine results in the generation of sodium chloride in stoichiometric amounts as an effluent which must be disposed of. The acetic acid generated in the next step must also be either disposed of or cleaned up for recycling. 

The aldol condensation can be carried out under either of two broad sets of conditions which lead to the product being determined by either kinetic or thermodynamic factors. To achieve kinetic control the enolate which is to serve as the nucleophile is generated stoichiometrically, usually with lithium as the counterion in an aprotic solvent. Under these conditions, enolates are both structurally and stereochemically stable. The electrophilic carbonyl compound is then added. Under these conditions, the structure of the reaction product is determined primarily by two factors (1) the structure of the initial enolate and (2) the stereoselectivity of the addition to the electrophilic carbonyl group. 

Control experiments and stoichiometric work were carried out in an attempt to discern if the Au was activating the alkyne as a tt-complex for nucleophilic attack by ammonia (Scheme 15.24). These experiments showed that alkyne is rapidly and... 

Oxidation Reactions. The advantage of the stable tetrafluoroborate reagent lies in its stoichiometric use in a variety of solvents under controlled reaction conditions in the absence of a nucleophilic anion. A particularly mild and selective oxidation of catechols to o-quinones can be effected with the title reagent and 1 equiv of triethylamine in acetonitrile below 0 °C (eq 2). 

Nncleophilic attack by carbanions on Pd rr-complexes provides an excellent method for carbon-carbon bond formation. The first example of natural product synthesis by the reaction of Pd rr-complex with carbon nucleophiles appears to be Holton s synthesis of prostanoids via treatment of an allylic amine with the stoichiometric amount of lithinm tetrachloropalladate and sodium diethyl malonate, followed by addition of diisopropy-lethylamine, which led to the formation of an isomerically pure bicyclic Pd-amine complex in 92% yield " (Scheme 18). The carbon nucleophile ends up a and trans to the dimethylamino group. Both regio- and stereochemistries must be controlled by the Me2N group. The amino diester intermediate was further transformed into Corey lactone diol, which had previously been converted to PGp2a in two steps and 80% overall yield. 

---