Nucleophiles hydrogen

When treated with a hydride reducing agent, such as LAH or sodium borohydride (NaBH4), aldehydes and ketones are reduced to alcohols  

These reactions were discussed in Section 13.4, and we saw that LAH and NaBH4 both function as delivery agents of hydride (H ). The precise mechanism of action for these reagents has been heavily investigated and is somewhat complex. Nevertheless, the simplified version shown in Mechanism 20.9 will be sufficient for our purposes. 

MECHANISM 20.9 THE REDUCTION OF KETONES OR ALDEHYDES WITH HYDRIDE AGENTS 

Lithium aluminium hydride LAH) functions as a delivery agent of hydride ions H ) 

In the first step of the mechanism, the reducing agent delivers a hydride ion, which attacks the carbonyl group, producing a tetrahedral intermediate. This intermediate is then treated with a proton source to yield the product. This simplified mechanism does not take into account many important observations, such as the role of the lithium cation (Li ). For example, when 

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Nucleophilic catalysis is catalysis by a general base (electron-pair donor) acting by donating its electron pair to an atom (usually carbon) other than hydrogen. Nucleophilic catalysis is exemplified by the imidazole-catalyzed hydrolysis of a phenyl acetate. (The tetrahedral intermediates are not shown.)... 

Cyclobutanes can be conveniently prepared from cyclobutene derivatives through electrophilic addition, catalytic hydrogenation, nucleophilic addition, cycloaddition as well as light-induced addition reactions. 

An ester group is displaced in the fourth step using a hydrogen nucleophile. 

Oxidation of the 1,2,4-dithiazoline (36) to the cation (34) with trityl tetrafluoroborate (74AP828) is an example of electrophilic attack at ring hydrogen. Nucleophilic attack with... 

Chapter 22 continues the study of carbonyl compounds with a detailed look at nucleophilic acyl substitution, a key reaction of carboxylic acids and their derivatives. Substitution at sp hybridized carbon atoms was introduced in Chapter 20 with reactions involving carbon and hydrogen nucleophiles. In Chapter 22, we learn that nucleophilic acyl substitution is a general reaction that occurs with a variety of heteroatomic nucleophiles. This reaction allows the conversion of one carboxylic acid derivative into another. Every reaction in Chapter 22 that begins with a carbonyl compound involves nucleophilic substitution. Chapter 22 also discusses the properties and chemical reactions of nitriles, compounds that contain a carbon-nitrogen triple bond. Nitriles are in the same carbon oxidation state as carboxylic acids, and they undergo reactions that form related products. 

This implied relationship between hydrogen basicity and hydrogen nucleophilicity (and its extended form involving other atomic centers) has been a major concern of physical organic chemists and is discussed in several of the chapters of this volume. 

All nucleophiles are bases (1). In fact, within the definition of Lewis (2), nucleophilicity is basicity. Following Ingold (3), however, physical-organic chemists have normally used the Brpnsted-Lowry definition (4, 5) of bases as affinity for protons. Likewise, nucleophilicity referred to affinity for nuclei of other elements, most often carbon (3). Another classification reserves basicity, and its counterpart acidity, for equilibrium measurements, while nucleophilicity and its counterpart electrophilicity refer to rate measurements (6). The terms carbon basicity and hydrogen nucleophilicity have been employed (7-9). This classification does not seem to have gained much acceptance. 

In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nucleophile forms a stable tetrahedral compound because the newly formed sp carbon is not bonded to a second electronegative atom. Thus, aldehydes and ketones undergo nucleophilic addition reactions with carbon and hydrogen nucleophiles, whereas they undergo nucleophilic addition-elimination reactions with nitrogen nucleophiles. 

Similar nucleophilic displacements do not appear to have been documented for compounds of the [1,5-a] series. However, compounds containing a 4,5-dihydroimidazole ring were subject to ring cleavage, for example (70) to (71) on reaction with hydrogen nucleophiles (Equation (7)) <90JCS(P1)385>. 

The cyclizations yield mostly the more stable epi-derivatives (e.g. (151)), with trans stereochemistry of the 0-lactam hydrogens. Nucleophilic displacement of the 7a-bromo substituent with thallium(I) phthalimide therefore results in the formation of the c/s derivative (153) [109,110]. 

List and co-workers demonstrated a Class IB process using enal-enone systems with a hydrogen nucleophile (Hantzsch ester 176) to give functionalized ring systems (Scheme 1.40) [57],... 

Over the years with the advent of milder and more controlled reaction conditions, the aldehyde component has increased in its diversity with a concomitant increase in functional group inter-compatibility. These changes also have enabled the extension of the nature of the active hydrogen (nucleophilic) species beyond enols. More recently, the utility of the Mannich reaction has been enhanced with enantioselective and catalytic variations. 

B.ii.b. Trapping of Acylpalladium Species with Carbon and Hydrogen Nucleophiles. 

Preparing Aldehydes and Ketones A Review Introduction to Nucleophilic Addition Reactions Oxygen Nucleophiles Nitrogen Nucleophiles Mechanism Strategies Sulfur Nucleophiles Hydrogen Nucleophiles Carbon Nucleophiles Baeyer-Villiger Oxidation of Aldehydes and Ketones Synthesis Strategies... 

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