N-Heterocyclic Carbene-Catalyzed Conjugate Umpolung for the Synthesis of γ-Butyrolactones

Abstract

The N-heterocyclic carbene-catalyzed conjugate Umpolung of differently substituted α,β-unsaturated aldehydes, e. g. cinnamaldehydes, α-methylcinnamaldehydes, and crotonaldehydes, is described. Coupling of these compounds with a variety of electrophilic aldehydes and ketones results in the selective formation of highly substituted β- and γ-butyrolactones.

Key words

carbenes - Umpolung - lactones - heterocycles - cyclization

References

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• 25a

  Lehmann, C. W. private communication to the Cambridge Structural Database (2004), deposition numbers CCDC-246600 and 250238.

• 25b

  Harms, K. private communication to the Cambridge Structural Database (2006), deposition numbers CCDC-603356 and 603357.

16

Under a different set of reaction conditions (t-BuOH, DBU, THF) and using two equivalents of electrophilic aldehyde, Bode et al. reported improved yields: ref. 7d.

17

The stereochemistry of the lactones 1, 7, 12, and 20 was assigned by X-ray and NMR analysis. The ¹H NMR data for the lactone ring hydrogens of 1a-h is very similar within the cis and trans series. The stereochemistry of the products 1 was therefore assigned by comparison of the NMR data for these compounds with that of cis-1d, whose structure was unequivocally established by X-ray structural analysis. The stereochemistry of lactones 7, 12, and 20 was assigned in an analogous manner. CCDC-246600 (cis-1d), CCDC-250238 (u-7b), CCDC-603356 (12c-I) and CCDC-603357 (20c-II) contain the crystallographic data (excluding structure factors) for this paper. [25] This data can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone]; e-mail: [e-mail].

18

Bode et al. found that when using cis-cinnamaldehyde the same stereochemical outcome as with trans-cinnamaldehyde was observed. Moreover, stopping the reaction of cis-cinnamaldehyde prior to completion a significant amount of trans-cinnamaldehyde was observed, showcasing the importance of homoenolate resonance structure IIb: ref. 7d.

20

Crotonaldehyde and α-methylcinnamaldehyde were reported to be unreactive under the conditions employed by Bode et al.: ref. 7 of ref. 7d.