Addition to aldehydes and

The next section explores the mechanism of nucleophilic addition to aldehydes and ketones There we 11 discuss their hydration a reaction m which water adds to the C=0 group After we use this reaction to develop some general principles we 11 then survey a number of related reactions of synthetic mechanistic or biological interest... 

This pattern of increased reactivity resulting from carbonyl group prolonalion has been seen before m nucleophilic additions to aldehydes and ketones (Section 17 6) and... 

Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds, its central theme is a fundfflnental reaction type, nucleophilic addition to carbonyl groups. The principles of nucleophilic addition to aldehydes and ketones developed here will be seen to have broad applicability in later chapters when transfonnations of various derivatives of carboxylic acids are discussed. 

Since the first reported directed aldol condensation using lithiated imines1. few methods concerning the diastereo- and enantioselectivity of their addition to aldehydes and ketones have been published. 

Phenyl trimethylsilylethyne (Chapter 20) undergoes a fluoride-ion-catalysed addition to aldehydes and ketones. This provides a remarkably mild, relatively non-basic method for the generation of an alkynyl anion or its equivalent. 

Scheme 7.4 illustrates some of the important synthetic reactions in which organolithium reagents act as nucleophiles. The range of reactions includes S/v2-(ype alkylation (Entries 1 to 3), epoxide ring opening (Entry 4), and formation of alcohols by additions to aldehydes and ketones (Entries 5 to 10). Note that in Entry 2, alkylation takes place mainly at the 7-carbon of the allylic system. The ratio favoring 7-alkylation... 

Another synthetically useful reaction involves the addition to aldehydes and ketones of carbanions, e.g. (100), derived from aliphatic nitro... 

In addition to aldehydes and a-diketones, a-ketoesters can also be used in the domino process, as shown by Tietze and coworkers [396]. Reaction of methyl pyruvate 2-791 with dimethylbarbituric acid (2-747) and the enol ether 2-792 in the presence of trimethyl orthoformate (TMOF) and a catalytic amount of EDDA gave the cycloadduct 2-793 in 84% yield (Scheme 2.176). 

Scheme 12. Shibasaki utilizes a Al-catalyzed asymmetric CN addition to aldehydes and a La-catalyzed asymmetric aldol in the total synthesis of epothilone A (2000).

Addition of HCN to acetone to form the cyanohydrin is still the main route to methyl methacrylate. Hydrocyanins can be converted to amino acids as well. The nitrile group can be easily converted to amines, carboxylic acids, amides, etc. Addition to aldehydes and activated alkenes can be done with simple base, but addition to unactivated alkenes requires a transition metal catalyst. The methods of HCN addition have been discussed by Brown [2],... 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

The next milestone in the realm of enantioselective organocatalysis was reached by Inoue and coworkers, who elegantly modernized the cyanohydrin reaction, first outlined by Bredig and Fiske in 1912. In these studies, a cyclic histidine-containing dipeptide (4) catalyzed the HCN addition to aromatic aldehydes with high enantioselectivities (97% ee) [Eq. (11.4)] a result that effectively paved the way for the field of peptide-catalyzed nucleophilic addition to aldehydes and imines ... 

Fig. 13). The cross-linked scandium-modified dendrimer was tested in a number of Lewis acid-catalyzed reactions, including Mukaiyama aldol additions to aldehydes and aldimines, Diels-Alder reactions, and Friedel-Crafts acylations. The dendritic catalyst was recovered by a simple filtration. The Mukaiyama aldol... 

The stereoselectivity of addition to aldehydes and ketones has been of considerable interest.111 112 With benzaldehyde, the addition of 2-butenylstannanes catalyzed by BF3 gives the syn isomer, irrespective of the stereochemistry of the butenyl group.113... 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

Addition reactions occur in compounds having n electrons in carbon-carbon double (alkenes) or triple bonds (alkynes) or carbon-oxygen double bonds (aldehydes and ketones). Addition reactions are of two types electrophilic addition to alkenes and alkynes, and nucleophilic addition to aldehydes and ketones. In an addition reaction, the product contains all of the elements of the two reacting species. 

Bromo-l-lithiocyclopropanes, readily obtained by transmetalation of 1,1-dibromocyclo-propanes with butyllithium in tetrahydrofuran at — 100 CC, undergo addition to aldehydes and ketones forming bromohydrins. On warming, before workup, the adducts from ketones (but not from aldehydes) eliminate lithium bromide and cyclizc to oxaspiropentanes, which may be rearranged to cyclobutanones by treatment with acids (Table 6).76-78... 

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