Nucleophilic addition overview

Nucleophilic additions to activated allenes have been reported fairly often. Since there are several good recent reviews of this area,131 only a brief overview is given here. 

During my early years as an assistant professor at the University of Kentucky, I demonstrated the synthesis of a simple quinone methide as the product of the nucleophilic aromatic substitution reaction of water at a highly destabilized 4-methoxybenzyl carbocation. I was struck by the notion that the distinctive chemical reactivity of quinone methides is related to the striking combination of neutral nonaromatic and zwitterionic aromatic valence bond resonance structures that contribute to their hybrid resonance structures. This served as the starting point for the interpretation of the results of our studies on nucleophile addition to quinone methides. At the same time, many other talented chemists have worked to develop methods for the generation of quinone methides and applications for these compounds in organic syntheses and chemical biology. The chapter coauthored with Maria Toteva presents an overview of this work. 

Very different and distinct ion chemistry has been observed in the reaction between the fragment ions obtained by electron ionization of tetramethoxygermane, Ge(OMe)4, and the parent neutral81. Reactions in this system proceed by nucleophilic addition followed by elimination of formaldehyde and/or elimination of methanol. An overview of the reactions of the different ions with Ge(OMe)4 is shown in Scheme 13 for the even electron ions, and in Scheme 14 for the radical ions originating from tetramethoxygermane. In these schemes, the neutral reagent of the ion/molecule reactions, Ge(OMe)4, is not shown for the sake of simplicity but the schemes include the neutral products that are eliminated upon addition of the reagent ion to the parent neutral molecule. 

The reactions of sulfenes are many and various and their presentation requires that they be sorted out into categories which, hopefully, help to show a measure of order in this abundance. We have chosen three main groups nucleophilic additions, cycloadditions, and thermal and photochemical processes. This arrangement is somewhat arbitrary, since the reactions are not all well-understood and, of those that are, not all fit perfectly into the chosen scheme. It is our view that this ordering, however imperfect, does serve the purpose of providing the reader with both an overview of sulfene chemistry and a means of gaining access to a specific piece of information. 

Anionic initiation has been accomplished in a variety of solvents, both polar and nonpolar. Typically, initiation can proceed by electron transfer reactions from alkali or alkaline earth metals, polycyclic aromatic radical anions, or alkali and magnesium ketyls. The other possibility includes the nucleophilic addition of organometallic compounds to the monomers. Related monofunctional initiators comprise alkyl derivatives of alkali metals or organomagnesium compounds such as Grignard reagents. Difunctional species are alkali derivatives of a-methylstyrene tetramer or the dimer of 1,1-diphenylethylene. An overview of the initiation process in carbanionic polymerization is given in Ref. [159]. 

Scheme 1.28 General overview for the gold-catalyzed nucleophilic additions to 1,6-enynes...

The addition of stabilized nucleophiles to activated ir-systems is one of the most widely used constructive methods in organic synthesis. This chapter has provided a selective overview of this still burgeoning area where further progress continues, especially in the area of stereocontrol. 

Additions to aromatic rings can become useful when radicals and acceptors are electronically paired. The additions of electrophilic radicals to electron rich aromatic rings are growing in importance and the additions of nucleophilic radicals to electron poor alkenes have long been of preparative value. This chapter can provide only a few representative examples of each class. Giese s book is recommended as a more thorough overview of additions to aromatic rings.232... 

The energy surface in Figure 4.34 gives an overview of three possible routes to add an electrophile and a nucleophile to a pi bond. The reactants are found in the upper left comer. In this example surface, the electrophile is a proton, delivered by an acid. The carbon-nucleophile bond must be made (the vertical axis) and the carbon-hydrogen bond must form (the horizontal axis) to reach the addition product in the lower right. Three idealized routes can occur. 

The above short overview provides the major synthetic methods leading to cyclopropanones and some of their derivatives. This basic knowledge will be used to discuss the various additions of nucleophiles across the carbonyl group of cyclopropanones, often generated in situ or in equilibrium with an adduct. 

Abstract In this chapter, the asymmetric organocatalytic conjugate addition of nucleophiles to Michael acceptors is covered. This report presents an overview of the most important developments and concepts of this area of catalysis organized by the type of nucleophile involved in the process. 

---