Synlett 2012; 23(10): 1427-1445
DOI: 10.1055/s-0031-1290982
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© Georg Thieme Verlag Stuttgart · New York

Stereocontrolled Synthesis of Functionalized Spirocyclic Compounds Based on Claisen Rearrangement and its Application to the Synthesis of Spirocyclic Sesquiterpenes and Pyrrolidinoindoline Alkaloids

Atsuo Nakazaki
a  Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya-shi, Aichi 464-8601, Japan
,
Susumu Kobayashi*
b  Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan, Fax: +81(4)71213671   Email: kobayash@rs.noda.tus.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 03 December 2011

Accepted after revision: 27 December 2011

Publication Date:
24 May 2012 (online)


Abstract

Spirocyclic scaffolds are embedded in many biologically active natural compounds, including candidates for medicines, perfumes and agricultural chemicals. Therefore, the development of efficient synthetic methods directed at those structures is strongly in demand. To this end, we have recently developed synthetic methodologies for two different spirocyclic frameworks, spiro[4.5]decanes and spirocyclic oxindoles, based on the Claisen rearrangement.

We have developed the Claisen rearrangement protocol by which bicyclic 2-(alkenyl)dihydropyrans with functionality at the 4-position can be transformed into spiro[4.5]decanes in good-to-excellent yields with excellent stereoselectivities. We applied this method to a concise total synthesis of several biologically active spirocyclic sesquiterpenes.

Related Claisen rearrangement in alkenyl pyranoindole systems can also be achieved. Thus, a one-pot intramolecular Ullmann coupling (IUC)/Claisen rearrangement sequence from 2-iodoindoles was found to provide spirocyclic oxindoles in good yields with excellent stereoselectivities. We applied this sequence to the synthesis of pyrrolidinoindoline alkaloids.

1 Introduction

2 Reported Claisen Rearrangement of 2-(Alkenyl)dihydro­pyran Systems

3 Claisen Rearrangement of Multi-Functionalized 2-(Alkenyl)dihydropyran Systems

3.1 Synthetic Strategy for Spiro[4.5]decanes

3.2 Synthesis of Claisen Substrates and their Rearrangement

3.3 Claisen Rearrangement in 2-(Z-Alkenyl)dihydropyran Systems

4 Application to the Synthesis of Spirocyclic Sesquiterpenes

4.1 Synthesis of Racemic Vetivane Sesquiterpenes

4.2 Synthesis of Racemic Gleenol and Axenol

4.3 Asymmetric Synthesis of (+)-α-Vetispirene and (–)-Agarospirol

4.4 Stereocontrolled Synthesis of (–)-Gleenol

4.5 Solvent Effects in the Claisen Rearrangement of 2-(Alkenyl)dihydropyrans

4.6 Stereocontrolled Synthesis of the Antimalarial Sesquiterpene, (+)-Axisonitrile-3

5 Claisen Rearrangement in Pyranoindoles Providing Spirocyclic Oxindoles

5.1 Synthetic Strategy for Spirocyclic Oxindoles

5.2 One-Pot Intramolecular Ullmann Coupling (IUC)/Claisen Rearrangement

6 Application to the Synthesis of Pyrrolidinoindoline Alkaloids; Synthesis of (–)-Flustramine B

7 Conclusion

 
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