Nucleophilic additions to carbonyl groups

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 fundamental reaction type nucleophilic addition to carbonyl groups The principles of nucleophilic addition to aide hydes and ketones developed here will be seen to have broad applicability m later chap ters when transformations of various derivatives of carboxylic acids are discussed... 

Cyanohydrin formation is reversible and the position of equilibrium depends on the steric and electronic factors governing nucleophilic addition to carbonyl groups described m the preceding section Aldehydes and unhindered ketones give good yields of cyanohydrins... 

Nucleophilic addition to carbonyl groups sometimes leads to a mixture of stereoisomeric products The direction of attack is often controlled by stenc factors with the nude ophile approaching the carbonyl group at its less hindered face Sodium borohydride reduction of 7 7 dimethylbicyclo[2 2 IJheptan 2 one illustrates this point... 

Generally, in the nucleophilic addition to carbonyl groups, either magnesium compounds or alkali metal compounds (such as the Li, Na and K derivatives) are used. In some cases even potassium carbonate or piperidine were used as the base for condensation with sulfones. Good results were obtained when concentrated aqueous NaOH was used under phase-transfer conditions288,297,333. 

Allylic derivatives are particularly important in the case of boranes, silanes, and stannanes. Allylic boranes effect nucleophilic addition to carbonyl groups via a cyclic TS that involves the Lewis acid character of the borane. 1,3-Allylic transposition occurs through the cyclic TS. 

Deprotonated trialkylstannanes are potent nucleophiles. Addition to carbonyl groups or iminium intermediates provides routes to a-alkoxy- and a-amino-alkylstannanes. 

Nucleophilic additions to carbonyl groups lead to alcohols which on dehydration, furnish alkenes70,71. This two-step protocol has been extremely useful for diene and polyene synthesis with wide variation in the carbonyl substrate and the nucleophilic addendum. Diene synthesis using aldol-type condensation as well as phenyl sulphonyl carbanion (the Julia reaction) are also discussed in this section. 

Nucleophilic addition to carbonyl groups aldehydes and ketones... 

NUCLEOPHILIC ADDITION TO CARBONYL GROUPS ALDEHYDES AND KETONES... 

In 1973, the group led by Prof. Adinolfi synthetized the antibiotic LL-Z1271a (63) [81] starting from ketolactone 139, obtained, in turn, by degradation of the diterpene marrubiin (9% overall yield). This synthesis basically consists of the formation of the 5-lactone C ring by nucleophilic addition to carbonyl group and subsequent lactonization (Scheme 11).. 

A. Cyclizations proceeding by nucleophilic additions to carbonyl groups 571... 

A. Cyclizations Proceeding by Nucleophilic Additions to Carbonyl Groups... 

Mechanism 10-2 Hydride Reduction of a Carbonyl Group 454 Summary Reactions of LiAIH4 and NaBH4 455 Summary Alcohol Syntheses by Nucleophilic Additions to Carbonyl Groups 457 10-12 Thiols (Mercaptans) 458 EssentialTerms 461 Study Problems 462... 

Key Mechanism 18-1 Nucleophilic Additions to Carbonyl Groups 841 18-12 TheWittig Reaction 843... 

CHAPTER 7 CHAPTER 8 CHAPTER 10 CHAPTER 11 CHAPTER 15 CHAPTER 17 CHAPTER 18 Acid-Catalyzed Dehydration of an Alcohol 313 Electrophilic Addition to Alkenes 330 Grignard Reactions 443 The Williamson Ether Synthesis 500 The Diels-Alder Reaction 684 Electrophilic Aromatic Substitution 757 Nucleophilic Additions to Carbonyl Groups 841 Formation of Imines 851 Formation of Acetals 856... 

The reaction has two steps nucleophilic addition of cyanide, followed by protonation of the anion. In fact, this is a general feature of all nucleophilic additions to carbonyl groups. 

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