Reactions and Syntheses

In the Organic Chemistry Laboratory

Lutz F. Tietze,Theophil Eicher,Ulf Diederichsen,Andreas Speicher,Nina Schützenmeister

• Publisher: Wiley-VCH
• Year: 2015
• ISBN:
  9783527688746
• Edition: 2
• Topic: Naturwissenschaften
• Subtopic: Physikalische & theoretische Chemie

The second edition of this classic text book has been completely revised, updated, and extended to include chapters on biomimetic amination reactions, Wacker oxidation, and useful domino reactions. The first-class author team with long-standing experience in practical courses on organic chemistry covers a multitude of preparative procedures of reaction types and compound classes indispensable in modern organic synthesis. Throughout, the experiments are accompanied by the theoretical and mechanistic fundamentals, while the clearly structured sub-chapters provide concise background information, retrosynthetic analysis, information on isolation and purification, analytical data as well as current literature citations. Finally, in each case the synthesis is labeled with one of three levels of difficulty. An indispensable manual for students and lecturers in chemistry, organic chemists, as well as lab technicians and chemists in the pharmaceutical and agrochemical industries.

Chapter 1
C–C Bond Formation

C–C bond formations are essential for the construction of the backbone of any organic compound, and their mechanistic description can be used as a general tool for their classification. Thus, in Sections 1.1–1.8, the focus is on transformations in which nucleophilic, electrophilic, radical, and pericyclic reactions as well as reactions mediated by organometallics and transition-metal compounds play the decisive role.

In Section 1.1, examples are given of nucleophilic additions to the carbonyl group of aldehydes, ketones, and derivatives of carboxylic acids (esters, anhydrides, etc.) as well as addition to acceptor-substituted olefins (Michael addition) and carbonyl olefination. In Section 1.2, alkylation reactions of aldehydes, ketones, carboxylic acids, and β-dicarbonyl compounds at their α- and γ-positions are described. In Section 1.3, reactions of the aldol and Mannich type and in Section 1.4, electrophilic and nucleophilic acylation reactions are depicted. Section 1.5 deals with reactions of alkenes proceeding via carbenium ions and Section 1.6 with transition-metal-catalyzed reactions such as the Heck reaction and Suzuki–Miyaura, Sonogashira, and metathesis reactions. In Section 1.7, pericyclic reactions such as cycloadditions, electrocyclic transformations, and sigmatropic reactions, and, finally, in Section 1.8 some basic radical reactions are described. Further transition-metal-catalyzed transformations such as the Wacker oxidation are described in Chapters 2 and 5.

1.1 Nucleophilic Addition to Aldehydes, Ketones, Carboxylic Acid Derivatives (Esters, Anhydrides), and α,β-Unsaturated Carbonyl Compounds; Carbonyl Olefination

1.1.1 (E)-4-Acetoxy-2-methyl-2-butenal

Topics:

Preparation of a C5-building block for vitamin A synthesis Allylic alcohols from ketones and vinyl Grignard compounds Acetylation of an allyl alcohol with allylic inversion Kornblum oxidation R–CH2–X → R–CH=O

(a) General

(E)-2-Methyl-2-butenal bearing an acetoxy group at the 4-position can be regarded as a functional isoprene unit and is used as a C₅-building block for the synthesis of terpenes by carbonyl olefination [1]. Thus, in the classical industrial vitamin A synthesis of BASF (cf. Section 4.1.5), (E)-4-acetoxy-2-methyl-2-butenal (1) is combined with the C₁₅-ylide 2 in a Wittig reaction to give vitamin A acetate 3:

Retrosynthesis of the target molecule 1 can be conducted in two directions (A/B) via the intermediates 4/5 and further by allylic inversions to allyl alcohols 6/7. These should result from the acetone derivatives 8/9 either by addition of allyl metals or by ethynylation followed by partial hydrogenation of the primarily formed acetylenic alcohols (approaches I/II). Both approaches I and II have been described in Refs [2, 3].

App...