Selectivity, chemo-, regio- and stereo

This chapter will briefly survey some basic physical and chemical properties of water as well as the possible relevance of these properties to aqueous organic chemistry in terms of reactivity, selectivity (chemo-, regio-, and stereo-), and phase-separations. 

Since the first Symposium was held, research activities have rapidly expanded as has the support provided by industry. Thus 104 Abstracts were submitted (an increase of 44 on the first symposium), closely related to the symposium theme. Moreover, the scientific contribution made by industry was also greater than at the previous symposium since this time a third of the papers was presented by researchers solely from industry (5 papers) or in collaboration with researchers from Universities (16 papers). The transformations studied were this time much more complex, covering all aspects of selectivity chemo, regio and stereo-selectivity having been frequently considered. 

Over the last few decades, transition-metal complexes have emerged as extremely useful synthetic tools for forming heterocycles. They often impart high selectivities (chemo, regio and stereo) seldom observed in classical synthetic methods. Moreover, the efficacy of these reactions, the possibility of employing mild conditions, and in many cases their use in catalytic quantities, all place metals as attractive precursors for orchestrating these transformations. ... 

The purpose of this chapter is to provide an introduction to the scope and limitations of radical cyclization reactions. Emphasis will be placed on the reactivity profile of radicals with respect to chemo-, regio-and stereo-selectivity. Because most sequential radical reactions include at least one cyclization, they are also presented in this chapter. The organization of this chapter is similar to the previous chapter on radical additions. However, the basic principles of radical reactions, selectivity requirements, methods to conduct radical reactions (including experimental techniques), and mechanisms are extensively discussed in the previous chapter, and these aspects will be reiterated rather sparingly. A reader who is not familiar with the principles of radical reactions as applied to synthesis should read the addition chapter (Chapter 4.1, this volume) first. 

The chemo-, regio-, and stereo-selective 1,3-dipolar cycloaddition of C-aryl-iV-phenylnitrones with 3,5-bis(arylidine)-l-methylpiperidin-4-ones produced mono- and bis-spiroisoxazolidines, with the former predominating.52 The 1,3-dipolar cycloaddition of five-membered cyclic nitrones with a, fl-unsaturated y-lactones provides an interesting example of a double asymmetric induction.53 Eu(fod)3 catalysed the ... 

Another rapidly progressing field is that of multistep reactions which occur in ordered sequences chemo-, regio- and stereo-selectively on a transition metal species. To this end, it is necessary to delay release of the desired product until the whole series of steps has been completed competitive terminations (such as hydride elimination) must be prevented or must only occur at low rates compared to the main sequence. An example, reported by Chiusoli in the late 50s, is offered by the nickel-catalyzed synthesis of methyl 2,5-heptadienoate from 2-butenyl chloride, acetylene, CO and methanol. The reaction is chemo-, regio- and stereo-selective the four molecules react in the order shown in Equation A3.4 (chemoselectivity) the butenyl group attacks the terminal allylic carbon rather than the internal one (regioselectivity) and acetylene insertion leads to a Z double bond (stereoselectivity). 

In an attempt to ameliorate this atuation Hoibest reasoned that introduction of a Lewis acid would facilitate the rate-detomining oiol formation. The whole reaction sequence would then be accelerated allowing the use of lower temperatures. This in turn would improve the chemo-, regio- and stereo-selectivity of the process. This proved to be a valid hypodiesis. 

The chemo-, regio- and stereo-selectivity observed in the Patemo-Buchi photocycloaddition make the reaction a valuable synthetic method as its numerous applications to targets in synthesis attest. This review will summarize the important mechanistic and synthetic advances. Knowledge of these precedents will likely initiate further scrutiny and applications of the reaction to the synthesis of architecturally complex targets. 

The main research efforts in transition metal mediated [3 -1- 2] cycloaddition can be categorized into the development of three important types of C3 synthon dimethylenemethane, 2-oxyallyl, and trimethy-lenemethane. This review summarizes some recent achievements up to the first quarter of 1989, and centers around these three synthons. Emphasis will be placed on the chemo-, regio- and stereo-selectivity of these reactions, their preparative aspects, and their synthetic potential. 

No doubt the Diels-Alder reaction will lend itself to further extensions of scope and selectivity. Nevertheless, the current state of the art and the pivotal applications of Diels-Alder adducts (XXX) for the efficient chemo-, regio- and stereo-selective syntheses of complex structures, e.g. via annulation processes (a, b) and/or cleavage reactions (c, d, e) speak for themselves (Scheme 6). An adequate treatise would vastly exceed the limits of this chapter. 

More recently the introduction of low-valent transition metal and lanthanoid based reducing systems, especially those based on titanium, has provided dramatic advances in efficiency and selectivity. It is now possible to select appropriate conditions for efficient coupling of all types of carbonyl compounds, often with high chemo-, regio- and stereo-selectivity. Moreover, imino- and thio-carbonyl derivatives are also coupled via pinacolic methodology. The coupling of imines to 1,2-diamines is particularly effective, with excellent control of vicinal stereochemistry. 

H. Ali and J.E. van Lier, Synthesis of Radiopharmaceuticals via Organotin Intermediates. 45 Organotin compounds react rapidly and chemo-, regio-, and stereo-selectively with a variety of reagents, and this has been exploited in the synthesis of pharmaceuticals with a radioactive label, particularly when the radioisotope has a short half-life. A second review covering similar ground is included in Patai s volume, as noted below. 

Almost every chapter so far has mentioned enolates in one form or another and their chemistry is central to organic synthesis. Now it is time to take stock of the various d2 reagents developed to play the role of enolates, to see what reactions they are particularly suited for, what chemo- regio-and stereo-selectivity they show, and some examples of their use in total synthesis. 

In these remarkable reactions, a series of electrophilic attacks on a bank of alkenes e.g. 257 is initiated by an electrophile. Each alkene adds to its neighbour until the bank is exhausted and essentially complete chemo-, regio- and stereo-selectivity is achieved. These reactions were discovered by W. S. Johnson41 and the idea came from nature where steroid synthesis is accomplished by very similar reactions. The main problem is terminating the sequence regioselectively and here allyl silanes (chapter 12) are most effective. 

Chemistry of the microbial oxidation by Candida boidinii SA051 was investigated. Chemo-, regio- and stereo- selectivity and substrate specificity of this microbial oxidation will be discussed. 

Isotopic labeling is a very useful technique in NMR studies of polymers. For exanqjle, NMR studies of polymers and copolymers prepared using C-enriched initiators have been carried out to obtain information about the chemo-, regio-, and stereo-selectivity of radicals derived from such initiators (93-95), In addition, and labeling has permitted the studies of chain ends obtained from F and P-containing initiators and chain transfer agents (72,95),... 

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