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Synlett 2016; 27(09): 1379-1382
DOI: 10.1055/s-0035-1561397
DOI: 10.1055/s-0035-1561397
letter
Enantioselective β-Alkylation of Aldehydes through an Organocatalyzed C–C Bond-Scission Reaction
Further Information
Publication History
Received: 26 December 2015
Accepted after revision: 22 January 2016
Publication Date:
01 March 2016 (online)
Abstract
A novel organocatalyzed C–C bond-scission reaction of saturated aldehydes containing a suitable leaving group at the β-position was used for the in situ formation of iminium intermediates, which were then captured by nucleophiles to achieve a direct enantioselective β-alkylation of aldehydes. Within short reaction times, the corresponding β-alkylated aldehyde products were obtained in high yields (48–87%) and with excellent enantioselectivities (84–98%).
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561397.
- Supporting Information
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References and Notes
- 1 Ahrendt KA, Borths CJ, MacMillan DW. C. J. Am. Chem. Soc. 2000; 122: 4243
- 2 List B, Lerner RA, Barbas CF. III. J. Am. Chem. Soc. 2000; 122: 2395
- 3a Berkessel A, Groeger H. Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in Asymmetric Synthesis. Wiley-VCH; Weinheim: 2005
- 3b Mukherjee S, Yang JW, Hoffmann S, List B. Chem. Rev. 2007; 107: 5471
- 3c Erkkilä A, Majander I, Pihko PM. Chem. Rev. 2007; 107: 5416
- 3d Enantioselective Organocatalysis: Reactions and Experimental Procedures. Dalko PI. Wiley-VCH; Weinheim: 2007
- 4a Zhang S.-L, Xie H.-X, Zhu J, Li H, Zhang X.-S, Li J, Wang W. Nat. Commun. 2011; 2: 211 ; doi: 10.1038/ncomms1214
- 4b Hayashi Y, Itoh T, Ishikawa H. Angew. Chem. Int. Ed. 2011; 50: 3920
- 4c Zeng X, Ni Q, Raabe G, Enders D. Angew. Chem. Int. Ed. 2013; 52: 2977
- 4d Zhao Y.-L, Wang Y, Hu X.-Q, Xu P.-F. Chem. Commun. 2013; 7555
- 5a Pirnot MT, Rankic DA, Martin DB. C, MacMillan DW. C. Science 2013; 339: 1593
- 5b Terrett JA, Clift MD, MacMillan DW. C. J. Am. Chem. Soc. 2014; 136: 6858
- 5c Petronijević FR, Nappi M, MacMillan DW. C. J. Am. Chem. Soc. 2013; 135: 18323
-
6 Mo J, Shen L, Chi YR. Angew. Chem. Int. Ed. 2013; 52: 8588
- 7a Notz W, Tanaka F, Barbas CF. III. Acc. Chem. Res. 2004; 37: 580
- 7b List B. Acc. Chem. Res. 2004; 37: 548
- 7c Córdova A. Acc. Chem. Res. 2004; 37: 102
- 7d Barbas CF. III. Angew. Chem. Int. Ed. 2008; 47: 42
- 7e Moyano A, Rios R. Chem. Rev. 2011; 111: 4703
- 7f Silvi M, Arceo E, Jurberg ID, Cassani C, Melchiorre P. J. Am. Chem. Soc. 2015; 137: 6120
- 8 Beeson TD, Mastracchio A, Hong J, Ashton K, MacMillan DW. C. Science 2007; 316: 582
-
9a Zhao X, Ruhl KE, Rovis T. Angew. Chem. Int. Ed. 2012; 51: 12330
-
9b Mo J, Yang R, Chen X, Tiwari B, Chi YR. Org. Lett. 2013; 15: 50
- 10a Jakobsen HJ, Lawesson S.-O, Marshall JT. B, Schroll G, Williams DH. J. Chem. Soc. B 1966; 940
- 10b Tiwari B, Zhang J, Chi YR. Angew. Chem. Int. Ed. 2012; 51: 1911
- 11 For an example of Michael addition of malonates to trans-cinnamaldehydes catalyzed by similar catalysts, see: Brandau S, Landa A, Franzen J, Marigo M, Jorgensen KA. Angew. Chem. Int. Ed. 2006; 45: 4305
- 12 The product was previously obtained through an amine-catalyzed tandem Michael/aldol reaction, see: Rueping M, Kuenkel A, Tato F, Bats JW. Angew. Chem. Int. Ed. 2009; 48: 3699
- 13 β-Alkylation Reaction; General Procedure A mixture of the appropriate malonate ester 8 (0.30 mmol, 3.0 equiv) and LiOH·H2O (4.2 mg, 0.10 mmol, 1.0 equiv) in CH2Cl2 (0.4 mL) was stirred at r.t. for 5 min. Catalyst 4a (3.2 mg, 0.01 mmol, 10 mol%) and aldehyde 3 (0.1 mmol, 1.0 equiv) were then added, and the mixture was stirred at r.t. until the reaction was complete. The mixture was directly transferred onto a silica gel column and purified by column chromatography (hexane–EtOAc) to give the pure product 9. Diethyl [(1R)-3-Oxo-1-phenylpropyl]malonate (9a) Colorless oil; yield: 25.3 mg (87%); [α]D 24 –38.1 (c 1.0, CHCl3; 96% ee). 1H NMR (500 MHz, CDCl3): δ = 9.60 (s, 1 H), 7.30–7.20 (m, 5 H), 4.21 (q, J = 7.0 Hz, 2 H), 4.03–3.99 (m, 1 H), 3.95 (q, J = 7.0 Hz, 2 H), 3.72 (d, J = 10 Hz, 1 H), 2.96–2.85 (m, 2 H), 1.26 (t, J = 7.0 Hz, 3 H), 1.00 (t, J = 7.0 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 200.0, 168.0, 167.4, 139.8, 128.7, 128.1, 127.5, 61.8, 61.4, 57.5, 47.4, 39.5, 14.0, 13.7. The enantiomeric excess of 9a was determined by chiral-stationary-phase HPLC analysis using a ChiralPak AD-H column (80:20 hexanes–i-PrOH at 0.5 mL/min; λ = 220 nm), major enantiomer: tR = 17.9 min; minor enantiomer: tR = 22.3 min.
- 14 We thank one of the referees for pointing out this important aspect.
For reviews, see:
For selected reviews, see:
Previously, β-scission of C–C bond of enamines has only been observed in their mass spectra via their radical cations, see:
For an example of amine-catalyzed oxidative α-scission of aldehydes, see: