Katritzky Advances in Heterocyclic Chemistry

1. Auflage 2013
ISBN: 978-0-12-420209-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 111, 292 Seiten

Reihe: Advances in Heterocyclic Chemistry

Established in 1960, Advances in Heterocyclic Chemistry is the definitive serial in the area-one of great importance to organic chemists, polymer chemists and many biological scientists. Written by established authorities in the field, the comprehensive reviews combine descriptive chemistry and mechanistic insight and yield an understanding of how the chemistry drives the properties. - One of great importance to organic chemists, polymer chemists and many biological scientists - Written by established authorities in the field, the comprehensive reviews combine descriptive chemistry and mechanistic insight and yield an understanding of how the chemistry drives the properties

Autoren/Hrsg.

Katritzky, Alan R.

Leseproben

Chapter One

Formation and Reactivity of 5-Aminopenta-2,4-Dienals

Useful Intermediates for Nitrogen Heterocycles Synthesis

Bernard Delpech,    Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette Cedex, France,    E-mail: [e-mail]

Abstract

5-Aminopenta-2,4-dienals, and specially their ,-disubstituted derivatives (Zincke aldehydes), are known for more than a century but their chemistry has not been highly exploited until recently. They are the most frequently prepared via the ring opening of 1-(2,4-dinitrophenyl)pyridinium salts (Zincke salts) with amines.

As these compounds are bisvinylogous formamides, and therefore push–pull dienes, they can behave either as nucleophilic or electrophilic species, and can be used for the construction of nitrogen heterocycles. Vanderwal discovered conditions for intramolecular cycloadditions involving Zincke aldehydes and indoles, allowing the synthesis of natural heterocyclic products. A thermic rearrangement of Zincke aldehydes into () dienamides has also been developed and applied to achieve the synthesis of polycyclic lactams.

5-Alkylaminopenta-2,4-dienals have been postulated by Marazano as possible biosynthetic intermediates in the formation of marine alkaloids of the manzamine family, and biomimetic approaches toward the skeleton of some of these compounds were developed, based on this proposal.

Keywords

5-Aminopenta-2,4-dienal; Biomimetic synthesis; Biosynthetic proposal; Cycloaddition; Glutaconaldehyde; Pyridinium salt; Zincke aldehyde; Zincke salt

1 Introduction

This chapter concerns the synthesis and the reactivity of 5-aminopenta-2,4-dienals (also called Zincke aldehydes when these compounds are ,-disubstituted). This topic has been reviewed by Becher in 1980 (80S589) but the chemistry of such derivatives has been neglected for a long time. A revival concerning these species emerged, first in 1998, when Marazano envisioned them as possible biosynthetic intermediates in the formation of the marine alkaloids of the manzamine family (98JA8026). More recently, Vanderwal sparked the interest for Zincke aldehydes by developing attractive methodologies, such as cycloadditions or rearrangements, with applications in the field of heterocyclic natural products synthesis (11JOC9555, 12JOC17).

As 5-aminopenta-2,4-dienals result formally from the hydrolysis of pyridinium salts, as illustrated for the parent compound 1 (Scheme 1), pyridines and pyridinium salts play a pivotal role, either for the preparation or for some reactions of these derivatives. A big part of their reactivity can be attributed to the fact that they are bisvinylogous formamides belonging to the class of push–pull (or donor-acceptor) dienes with electron-donating (amino group) and electron-withdrawing (formyl group) substituents at both ends of the dienic moiety.

Scheme 1

The first compounds of this family were obtained at the beginning of the twentieth century by Zincke, via the opening of 1-(2,4-dinitrophenyl)pyridinium salts with amines (1904LA361, 1904LA296), and also by König (1904JPR105) via the treatment of pyridines with cyanogen bromide in the presence of an amine. Since that time, most of the 5-aminopenta-2,4-dienals have been prepared following the Zincke method and, therefore, the synthesis of these compounds is strongly related to the Zincke reaction (see Section 2).

The interest for aminopentadienals was revived when Marazano postulated that some of their ,4-dialkyl derivatives could be key intermediates in the biosynthetic pathway toward alkaloids isolated from marine sponges and belonging to the manzamine family (98JA8026, 02JOC1890, 03JOC8883, 05EJO1302, 10CEJ3594, 11CEJ9907). These species could result from the condensation of malonaldehyde with long chain 1,?-aminoaldehydes, (see Scheme 2 for a proposal concerning manzamine A).

Scheme 2

More recently, Vanderwal developed a base mediated intramolecular cycloaddition involving Zincke aldehydes (see Section 5.3), which was exploited in the synthesis of indolic natural products. He discovered also a thermal rearrangement of Zincke aldehydes (see Section 5.4) with interesting applications for the construction of polycyclic heterocyclic compounds.

The main object of this chapter concerns preparative methods for 5-aminopenta-2,4-dienals, some of their structural characteristics and the development of their chemistry, principally since the review of Becher (80S589). A special attention is focused on the use of these species as a tool toward the synthesis of heterocyclic compounds and natural products.

2 The Zincke Reaction

Zincke reported in 1904 that the treatment of 1-(2,4-dinitrophenyl)pyridinium chloride 2 with aniline gave 1-phenylpyridinium chloride via ring opening, amine exchange and cyclization (1904LA361, 1904LA296) (Scheme 3). This reaction, which has been reviewed (02OPP585, 05MI1), is interesting for the preparation of pyridinium salts, which cannot be easily obtained by alkylation of pyridines. The 1-(2,4-dinitrophenyl)pyridiniums chlorides (Zincke salts) are prepared by treatment of the corresponding pyridines with 1-chloro-2,4-dinitrobenzene. Applications of the Zincke reaction in the field of natural products synthesis, and particularly in order to access pyridinium macrocycles isolated from marine sponges, have been reported by Marazano (91JCS(CC)625, 93JOC2052, 94H811, 97JOC729, 98JA8026, 99JOC4528, 02JOC6474).

Scheme 3

The Zincke reaction is important in the context of the formation of 5-aminopenta-2,4-dienals if one looks at the intermediates and at the mechanism of this reaction, which can be considered as an internal SN(ANRORC) (Addition of the Nucleophile, Ring Opening and Ring Closure) (99AHC87, 81T3423). The first steps lead to the formation of a 5-aminopenta-2,4-dien-1-iminium chloride, often called König’s salt and which can be isolated, affording the pyridinium salt, generally by heating, via electrocyclization and elimination processes, as summarized in Scheme 4. The rate-determining step has been shown to be the electrocyclization (70JA5641, 70JA5646).

Scheme 4

As can be seen from the structure of the König’s salt, and also of the primary opened compound, its hydrolysis can lead to 5-phenylaminopenta-2,4-dienal. However, it is better to conduct the first step of the Zincke reaction with a secondary amine in order to avoid the formation of the pyridinium salt. This has been done by Zincke in 1905 (1905LA107) when he chose -methylaniline as the amine partner (Scheme 5).

Scheme 5

It is difficult to stop the opening of the Zincke salt at the stage of the incorporation of only one equivalent of amine, as shown in Scheme 6, the rate of formation of the symmetrical aminopentadieniminium 4 from 3 being greater than that of the opening of the Zincke salt 2 by the amine leading to 3 (74CCC2056).

Scheme 6

This observation is of consequence for the synthesis of aminopentadienals since two equivalents of the amine are generally required for the formation of the iminium derivative and one is lost in the hydrolytic step. Therefore, the basic hydrolysis of a König’s salt is not the best method in the case of expensive or highly functionalized amines.

It is interesting to note that the same aminopentadieniminium salt is obtained when the Zincke salt prepared from 3-picoline is treated first with diethylamine and then with butylamine or when the order of introduction of the amines is inverted (07JOC5916). There is no trace of the regioisomer with the methyl group close to the diethylamino one and the basic hydrolysis leads mostly to the ,-diethylaminopentadienal (Scheme 7).

Scheme 7

The major or exclusive formation of the compound with the substituent at position 2, by basic hydrolysis of an aminopentadieniminium salt, is a general phenomenon (see Section 3.2.2).

As can be deduced from the above considerations, the opening of a Zincke salt by an amine (first steps of the Zincke reaction) is a powerful method with the aim of preparing 5-aminopenta-2,4-dienals and has been intensively used for this purpose.

3 Preparation of 5-Aminopenta-2,4-Dienals

5-Aminopenta-2,4-dienals are generally obtained as the sole (,) geometric isomer, except for some derivatives that are -alkylated. The more the compounds are substituted (on the nitrogen and even at the carbons), the more they are stable.

3.1 The Parent Compound

Unsubstituted (,)-5-aminopenta-2,4-dienal (1) is a rather unstable compound, losing readily water to give pyridine, and its first preparative synthesis has been published in 1981 (81AGE881). After opening of a special pyridinium...