RSS-Feed abonnieren
DOI: 10.1055/s-2006-942447
N-Heterocyclic Carbene-Catalyzed Conjugate Umpolung for the Synthesis of γ-Butyrolactones
Publikationsverlauf
Publikationsdatum:
07. Juli 2006 (online)
![](https://www.thieme-connect.de/media/synthesis/200614/lookinside/thumbnails/10.1055-s-2006-942447-1.jpg)
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
- 1
Seebach D. Angew. Chem., Int. Ed. Engl. 1979, 18: 239 - 2 For example the use of deprotonated dithianes as masked carbonyl anion synthons has become a very popular stoichiometric approach, see:
Seebach D.Corey EJ. J. Org. Chem. 1975, 40: 231 -
3a
Eisch JJ. J. Organomet. Chem. 1995, 500: 101 -
3b
Pohl M.Lingen B.Müller M. Chem. Eur. J. 2002, 8: 5288 -
4a
Wöhler F.Liebig J. Ann. Pharm. 1832, 3: 249 -
4b
Lapworth A. J. Chem. Soc. 1903, 83: 995 -
4c
Breslow R. J. Am. Chem. Soc. 1958, 80: 3719 -
5a
Stetter H.Kuhlmann H. Org. React. 1991, 40: 407 -
5b
Stetter H.Kuhlmann H. Chem. Ber. 1976, 109: 2890 - For excellent reviews, see:
-
6a
Ahlbrecht H.Beyer U. Synthesis 1999, 365 -
6b
Hoppe D. Angew. Chem., Int. Ed. Engl. 1984, 23: 932 -
6c
Westiuk N. Tetrahedron 1983, 39: 205 - See also:
-
6d
Hoppe D.Zschage O. Angew. Chem., Int. Ed. Engl. 1989, 28: 69 -
6e
Zschage O.Hoppe D. Tetrahedron 1992, 48: 5657 - For N-heterocyclic carbene catalyzed conjugate Umpolung and related reactions, see:
-
7a
Chow KY.-K.Bode JW. J. Am. Chem. Soc. 2004, 126: 8126 -
7b
Reynolds NT.Read de Alaniz J.Rovis T. J. Am. Chem. Soc. 2004, 126: 9518 -
7c
Burstein C.Glorius F. Angew. Chem. Int. Ed. 2004, 43: 6205 -
7d
Sohn SS.Rosen EL.Bode JW. J. Am. Chem. Soc. 2004, 126: 14370 -
7e
He M.Bode JW. Org. Lett. 2005, 7: 3131 -
7f
Sohn SS.Bode JW. Org. Lett. 2005, 7: 3873 -
7g
Chan A.Scheidt K. A. Org. Lett. 2005, 7: 905 -
7h
Reynolds NT.Rovis T. J. Am. Chem. Soc. 2005, 127: 16406 -
7i
Zeitler K. Org. Lett. 2006, 8: 637 - Very recently, the formation of spiro γ-butyrolactones by conjugate Umpolung using cyclic 1,2-diketones as the electrophiles was reported:
-
7j
Nair V.Vellalath S.Poonoth M.Mohan R.Suresh E. Org. Lett. 2006, 8: 507 - For N-heterocyclic carbene catalyzed transesterification reactions, see:
-
8a
Grasa GA.Kissling RM.Nolan SP. Org. Lett. 2002, 4: 3583 -
8b
Grasa GA.Guveli T.Singh R.Nolan SP. J. Org. Chem. 2003, 68: 2812 -
8c
Singh R.Kissling RM.Letellier M.-A.Nolan SP. J. Org. Chem. 2004, 69: 209 -
8d
Singh R.Nolan SP. Chem. Commun. 2005, 5456 -
8e
Nyce GW.Lamboy JA.Connor EF.Waymouth RM.Hedrick JL. Org. Lett. 2002, 4: 3587 -
8f
Connor EF.Nyce GW.Myers M.Mock A.Hedrick JL. J. Am. Chem. Soc. 2002, 124: 914 -
8g
Nyce GW.Glauser T.Connor EF.Mock A.Waymouth RM.Hedrick JL. J. Am. Chem. Soc. 2003, 125: 3046 - For a related amidation, see:
-
8h
Schmidt MA.Movassaghi M. Org. Lett. 2005, 7: 2453 - For the N-heterocyclic carbene catalyzed kinetic resolution of alcohols, see:
-
9a
Suzuki Y.Yamauchi K.Muramatsu K.Sato M. Chem. Commun. 2004, 2770 -
9b
Kano T.Sasaki K.Maruoka K. Org. Lett. 2005, 7: 1347 - For N-heterocyclic carbene catalyzed benzoin condensations, see:
-
10a
Enders D.Niemeier O.Balensiefer T. Angew. Chem. Int. Ed. 2006, 45: 1463 -
10b
Enders D.Niemeier O. Synlett 2004, 2111 -
10c
Enders D.Kallfass U. Angew. Chem. Int. Ed. 2002, 41: 1743 -
10d
Hachisu Y.Bode JW.Suzuki K. J. Am. Chem. Soc. 2003, 125: 8432 -
10e
Hachisu Y.Bode JW.Suzuki K. Adv. Synth. Catal. 2004, 346: 1097 - See also:
-
10f
Dudding T.Houk KN. Proc. Natl. Acad. Sci. U.S.A. 2004, 101: 5770 -
10g
Pesch J.Harms K.Bach T. Eur. J. Org. Chem. 2004, 2025 - For N-heterocyclic carbene catalyzed Stetter reactions, see:
-
11a
Kerr MS.Read de Alaniz J.Rovis T. J. Am. Chem. Soc. 2002, 124: 10298 -
11b
Kerr MS.Rovis T. J. Am. Chem. Soc. 2004, 126: 8876 -
11c
Read de Alaniz J.Rovis T. J. Am. Chem. Soc. 2005, 127: 6284 -
11d
Mattson AE.Bharadwaj AR.Scheidt KA. J. Am. Chem. Soc. 2004, 126: 2314 -
11e
Liu Q.Rovis T. J. Am. Chem. Soc. 2006, 128: 2552 -
11f
Braun RU.Zeitler K.Müller TJJ. Org. Lett. 2001, 3: 3297 -
11g
Bharadwaj AR.Scheidt KA. Org. Lett. 2004, 6: 2465 -
11h
Myers MC.Bharadwaj AR.Milgram BC.Scheidt KA. J. Am. Chem. Soc. 2005, 127: 14675 - For some other N-heterocyclic carbene catalyzed reactions, see:
-
12a
Suzuki Y.Toyota T.Imada F.Sato M.Miyashita A. Chem. Commun. 2003, 1314 -
12b
Song JJ.Tan Z.Reeves JT.Gallou F.Yee NK.Senanayake CH. Org. Lett. 2005, 7: 2193 -
12c
Song JJ.Gallou F.Reeves JT.Tan Z.Yee NK.Senanayake CH. J. Org. Chem. 2006, 71: 1273 -
12d
Duong HA.Cross MJ.Louie J. Org. Lett. 2004, 6: 4679 -
12e
Mattson AE.Scheidt KA. Org. Lett. 2004, 6: 4363 -
12f
Fischer C.Smith SW.Powell DA.Fu GC. J. Am. Chem. Soc. 2006, 128: 1472 - For the stoichiometric use of N-heterocyclic carbenes as reagents, see:
-
13a
Nair V.Bindu S.Sreekumar V.Rath NP. Org. Lett. 2003, 5: 665 -
13b
Rigby JH.Wang Z. Org. Lett. 2002, 4: 4289 -
13c
Enders D.Breuer K.Raabe G.Runsink J.Teles JH. Liebigs Ann. Chem. 1996, 2019 -
13d
Nair V.Bindu S.Sreekumar V. Angew. Chem. Int. Ed. 2004, 43: 5130 -
13e
Ma C.Yang Y. Org. Lett. 2005, 7: 1343 - For excellent reviews on N-heterocyclic carbenes in organocatalysis, see:
-
14a
Enders D.Balensiefer T. Acc. Chem. Res. 2004, 37: 534 -
14b
Johnson JS. Angew. Chem. Int. Ed. 2004, 43: 1326 -
14c
Christmann M. Angew. Chem. Int. Ed. 2005, 44: 2632 -
14d
Zeitler K. Angew. Chem. Int. Ed. 2005, 44: 7506 - For general reviews on N-heterocyclic carbenes, see:
-
14e
Herrmann WA. Angew. Chem. Int. Ed. 2002, 41: 1291 -
14f
Herrmann WA.Köcher C. Angew. Chem., Int. Ed. Engl. 1997, 36: 2162 -
14g
Arduengo AJ.Krafczyk R. Chem. Unserer Zeit 1998, 32: 6 -
14h
Bourissou D.Guerret O.Gabbaï FP.Bertrand G. Chem. Rev. 2000, 100: 39 -
14i
Perry M. C.Burgess K. Tetrahedron: Asymmetry 2003, 14: 951 -
14j
Cesar V.Bellemin-Laponnaz S.Gade L. H. Chem. Soc. Rev. 2004, 33: 619 - For excellent reviews on modern organocatalysis, see:
-
15a
Seayad J.List B. Org. Biomol. Chem. 2005, 3: 719 -
15b
Dalko PI.Moisan L. Angew. Chem. Int. Ed. 2004, 43: 5138 -
15c
Dalko PI.Moisan L. Angew. Chem. Int. Ed. 2001, 40: 3726 -
15d
Berkessel A.Gröger H. Asymmetric Organocatalysis VCH; Weinheim: 2004. -
19a
Glorius F.Altenhoff G.Goddard R.Lehmann C. Chem. Commun. 2002, 2704 - For the successful application of these ligands in the Suzuki cross-coupling of sterically hindered aryl chlorides, see:
-
19b
Altenhoff G.Goddard R.Lehmann CW.Glorius F. Angew. Chem. Int. Ed. 2003, 42: 3690 -
19c
Altenhoff G.Goddard R.Lehmann CW.Glorius F. J. Am. Chem. Soc. 2004, 126: 15195 - 21 For lactones in natural products, see:
Seitz M.Reiser O. Curr. Opin. Chem. Biol. 2005, 9: 285 - For the first step of the synthesis of aldehyde 23, see:
-
22a
Boatman S.Harris TM.Hauser CR. J. Org. Chem. 1965, 30: 3321 - For the Heck reaction methodology used in the second step, see:
-
22b
Battistuzzi G.Cacchi S.Fabrizi G. Org. Lett. 2003, 5: 777 - 23
Stott K.Keeler J.Van Q N.Shaka AJ. J. Magn. Reson. 1997, 125: 302 - 24
Pearson AJ.Mesaros EF. Org. Lett. 2002, 4: 2001 -
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.
References
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.
17The 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: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk.
18Bode 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.
20Crotonaldehyde and α-methylcinnamaldehyde were reported to be unreactive under the conditions employed by Bode et al.: ref. 7 of ref. 7d.