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Synthesis 2003(7): 0961-1008
DOI: 10.1055/s-2003-39171
REVIEW
© Georg Thieme Verlag Stuttgart ˙ New York

Recent Advances in Asymmetric [3,3]-Sigmatropic Rearrangements

Udo Nubbemeyer
Institut für Organische Chemie und Abteilung für Lehramtskandidaten, Fachbereich Chemie und Pharmazie, Johannes Gutenberg-Universität, Duesbergweg 10-14, 55099 Mainz, Germany
Fax: +49(6131)3924533; e-Mail: nubbemey@mail.uni-mainz.de;
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Publication History

Received 3 December 2002
Publication Date:
09 May 2003 (online)

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Abstract

The synthesis of new complex structures is still a challenge in preparative organic chemistry. Focusing on the generation of defined stereogenic centers, the [3,3]-sigmatropic rearrangements are known as reliable reactions. Always, a highly ordered transition state must be passed through, which allows the shift of chiral information from the reactant into the nascent product. Generally, the complete [1,3]- and, frequently, the [1,4]-chirality transfer enables one to predict the configuration of the new centers.

This review focuses on Claisen and Cope rearrangements, which adopt the chiral information via a so termed asymmetric induction. This means, that the directing chiral subunit is placed outside of the six centers of the rearrangement system being reorganized during the course of the [3,3]-sigmatropic reaction.

Reviewing the literature since 1995, enantioselective Claisen rearrangements have been widely investigated. The unique sense of the reaction allows the conversion of an easily accessible C atom-heteroatom bond into a new C-C bond making this rearrangement useful for constructing complex molecules. In contrast, the Cope rearrangement is reversible. One crucial requirement is to force the process to completion with respect to the desired product. Hence ‘enantioselective Cope rearrangements’ are always included as one step in a reaction cascade to guarantee the unique sense of the process. Analyzing such reactions in more detail, the chirality-inducing step is run prior to the Cope rearrangement. Thus, the [3,3]-sigma­tropic rearrangement is conducted under the well-known [1,3]-chirality transfer conditions.

  • 1 Introduction

  • 2 Asymmetric Claisen Rearrangements: Classification

  • 3 Remote Stereocontrol in Claisen Rearrangements

  • 3.1 Stereogenic Center at C1

  • 3.2 Stereogenic Center at C6

  • 3.3 Stereogenic Center in Other Positions

  • 4 Auxiliary Control in Claisen Rearrangements

  • 4.1 Auxiliary Attached to Position X

  • 4.2 Auxiliary Attached to Position Y

  • 4.3 Auxiliary Attached to Position Z

  • 4.4 Miscellaneous

  • 5 Chiral Metal Complex Directed Claisen Rearrangements

  • 6 Enantioselective Catalyzed Claisen Rearrangements

  • 7 Asymmetric Cope Rearrangements

  • 7.1 Remote Stereocontrol in Cope Rearrangements

  • 7.2 Auxiliary Control in Cope Rearrangements

  • 7.3 Catalyst Control in Cope Rearrangements

  • 8 Summary

Key words

asymmetric Claisen rearrangement - Cope rearrangement - chiral auxiliary - chiral metal complex - chiral catalyst

21

For the discussion of a stepwise reaction mechanism see chapter 6 and the literature cited therein.

31

The Ireland-type rearrangements are characterized by metal enolates bearing chiral ligands. These reactions are discussed in chapter 5 (vide infra).

38

The reversibility had been proven by subjecting the pure product to the reaction conditions resulting in the Claisen reactant and potentially some other diastereomers.

51

The use of Hünig’s base resulted in a disappointing yield of only 36%. Barton’s base: pentaisopropylguanidine.

53

The boron ester formation was crucial for the Claisen rearrangement to proceed. In the absence of an o-OH group the reaction failed. The o-OH group could be replaced by a carboxylic acid function but such conversion resulted a lower yield and a decreased enantioselectivity. Additionally some p-product was isolated.

56

However this special variant did obviously not suffer from any von Braun type degradation or from any [2+2]-cycloadditions as reported in previous publications and references cited therein).

59

Reacting non-symmetric enol ethers the palladium-catalyzed version preferentially gave the less-substituted vinyl systems. The rearrangement passed through a boat-like transition state. In contrast the proton-catalyzed reaction gave the higher substituted vinylether and the thermal rearrangement (100 °C) passed through a chair-like transition state. Regio- and stereochemistry could be influenced by a careful choice of the reaction conditions. For the discussion of a two-step reaction mechanism see Overman amidate rearrangements. [67]

63

The rhodium catalyst did not influence the Claisen rearrangement step.

77

The 3,5-rearrangement can be described as an iminium salt olefin addition and a subsequent fragmentation (cation stabilization). No new stereogenic center was constructed.

83

n-BuLi was found to be the base of choice to induce the anionic amino Cope rearrangements. Experiments using alternative strong bases such as LDA and KHMDS failed.

86

In contrast to the Oppolzer sultams the corresponding Evans auxiliary gave only moderate chiral induction of about 50% de building-up the new stereogenic center.

93

For a mechanistic discussion concerning the stereochemical outcome of the asymmetric catalyzed cyclopropanation see the original references.