Highly Enantioselective Direct
Aldol Reactions Catalyzed by Proline Derivatives Based
on a Calix[4]arene Scaffold in the Presence of
Water

Zheng-Yi Li; Jia-Wen Chen; Leyong Wang; Yi Pan

doi:10.1055/s-0029-1217710

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2009(14): 2356-2360
DOI: 10.1055/s-0029-1217710

LETTER

Highly Enantioselective Direct Aldol Reactions Catalyzed by Proline Derivatives Based on a Calix[4]arene Scaffold in the Presence of Water

Zheng-Yi Li^a, Jia-Wen Chen^a, Leyong Wang*^a, Yi Pan*^b
^a Key Laboratory of Mesoscopic Chemistry of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. of China
Fax: +86(25)83317761; e-Mail: lywang@nju.edu.cn;
^b State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, P. R. of China
e-Mail: yipan@nju.edu.cn;

Further Information

Publication History

Received 3 April 2009
Publication Date:
31 July 2009 (online)

Abstract
Full Text
References
Supplementary Material

Buy Article Permissions and Reprints All articles of this category

Abstract

A series of proline-derived organocatalysts based on a calix[4]arene scaffold have been developed to catalyze direct aldol reactions in the presence of water. Under the optimal conditions, high yields (up to >99%), good enantioselectivities (up to >99% ee) and diastereoselectivities (up to 90:10) were obtained.

Key words

proline - calix[4]arene - organocatalyst - aldol reaction - water

Supporting Information

References and Notes

1a Breslow R. Acc. Chem. Res. 2004, 37: 471

Search in Google Scholar
1b Lindström UM. Chem. Rev. 2002, 102: 2751

Search in Google Scholar
1c Li C.-J. Chem. Rev. 2005, 105: 3095

Search in Google Scholar
1d Pirrung MC. Chem. Eur. J. 2006, 12: 1312

Search in Google Scholar
1e Blackmond DG. Armstrong A. Coombe V. Wells A. Angew. Chem. Int. Ed. 2007, 46: 3798

Search in Google Scholar
1f Lindström UM. Andersson F. Angew. Chem. Int. Ed. 2006, 45: 548

Search in Google Scholar
1g Jung Y. Marcus RA. J. Am. Chem. Soc. 2007, 129: 5492

Search in Google Scholar
2a Berkessel A. Gröger H. Asymmetric Organocatalysis Wiley-VCH; Weinheim / Germany: 2005.
2b Dean SM. Greenberg WA. Wong C.-H. Adv. Synth. Catal. 2007, 349: 1308

Search in Google Scholar
3a Mlynarski J. Paradowska J. Chem. Soc. Rev. 2008, 37: 1502

Search in Google Scholar
3b Brogan AP. Dickerson TJ. Janda KD. Angew. Chem. Int. Ed. 2006, 45: 8100

Search in Google Scholar
4a Hayashi Y. Sumiya T. Takahashi J. Gotoh H. Urushima T. Shoji M. Angew. Chem. Int. Ed. 2006, 45: 958

Search in Google Scholar
4b Hayashi Y. Aratake S. Okano T. Takahashi J. Sumiya T. Shoji M. Angew. Chem. Int. Ed. 2006, 45: 5527

Search in Google Scholar
4c Aratake S. Itoh T. Okano T. Usui T. Shoji M. Hayashi Y. Chem. Commun. 2007, 2524
4d Hayashi Y. Aratake S. Itoh T. Okano T. Sumiya T. Shoji M. Chem. Commun. 2007, 957
4e Aratake S. Itoh T. Okano T. Nagae N. Sumiya T. Shoji M. Hayashi Y. Chem. Eur. J. 2007, 13: 10246

Search in Google Scholar
5a Mase N. Nakai Y. Ohara N. Yoda H. Takabe K. Tanaka F. Barbas CF. J. Am. Chem. Soc. 2006, 128: 734

Search in Google Scholar
5b Ramasastry SSV. Albertshofer K. Utsumi N. Barbas CF. Org. Lett. 2008, 10: 1621

Search in Google Scholar
6 Huang J. Zhang X. Armstrong DW. Angew. Chem. Int. Ed. 2007, 46: 9073

Crossref Search in Google Scholar
7 Maya V. Raj M. Singh VK. Org. Lett. 2007, 9: 2593

Crossref Search in Google Scholar
8a Zhu M.-K. Xu X.-Y. Gong L.-Z. Adv. Synth. Catal. 2008, 350: 1390

Search in Google Scholar
8b Zhao J.-F. He L. Jiang J. Tang Z. Cun L.-F. Gong L.-Z. Tetrahedron Lett. 2008, 49: 3372

Search in Google Scholar
9 Guizzetti S. Benaglia M. Raimondi L. Celentano G. Org. Lett. 2007, 9: 1247

Crossref PubMed Search in Google Scholar
10 Wu Y. Zhang Y. Yu M. Zhao G. Wang S. Org. Lett. 2006, 8: 4417

Crossref Search in Google Scholar
11 Zu L. Xie H. Li H. Wang J. Wang W. Org. Lett. 2008, 10: 1211

Crossref PubMed Search in Google Scholar
12 Giacalone F. Gruttadauria M. Meo PL. Riela S. Noto R. Adv. Synth. Catal. 2008, 350: 2747

Crossref Search in Google Scholar
13 Zheng C. Wu Y. Wang X. Zhao G. Adv. Synth. Catal. 2008, 350: 2690

Crossref Search in Google Scholar
14a Zhang S.-P. Fu X.-K. Fu S.-D. Pan J.-F. Catal. Commun. 2009, 10: 401

Search in Google Scholar
14b Zhang S.-P. Fu X.-K. Fu S.-D. Tetrahedron Lett. 2009, 50: 1173

Search in Google Scholar
15a Shimizu S. Kito K. Sasaki Y. Hirai C. J. Chem. Soc., Chem. Commun. 1997, 1629
15b Shimizu S. Suzuki T. Shirakawa S. Sasaki Y. Hirai C. Adv. Synth. Catal. 2002, 344: 370

Search in Google Scholar
15c Nomura E. Taniguchi H. Kawaguchi K. Otsuji Y. Chem. Lett. 1991, 2167
15d Nomura E. Taniguchi H. Kawaguchi K. Otsuji Y. J. Org. Chem. 1993, 58: 4709

Search in Google Scholar
15e Taniguchi H. Nomura E. Chem. Lett. 1988, 1773
15f Komiyama M. Isaka K. Shinkai S. Chem. Lett. 1991, 937
16 Xu Z.-X. Li G.-K. Chen C.-F. Huang Z.-T. Tetrahedron 2008, 64: 8668

Crossref Search in Google Scholar
17 Gutsche CD. Iqbal M. Org. Synth. 1990, 68: 234

Search in Google Scholar
18 Dondoni A. Marra A. Scherrmann M.-C. Casnati A. Sansone F. Ungaro R. Chem. Eur. J. 1997, 3: 1774

Crossref Search in Google Scholar
25a Paradowska J. Stodulski M. Mlynarski J. Adv. Synth. Catal. 2007, 349: 1041

Search in Google Scholar
25b Ma G.-N. Zhang Y.-P. Shi M. Synthesis 2007, 197

19

Analytical data for compound 1: Yield: 47%. White solid, mp 233-235 ˚C. [α]_D ^²6 +21.6 (c = 1.0, CHCl₃). ^¹H NMR (300 MHz, DMSO-d ₆): δ = 1.11 [s, 9H, C(CH₃)₃], 1.16 [s, 18H, 2 × C(CH₃)₃], 1.17 [s, 9H, C(CH₃)₃], 3.34 (d, J = 8.1 Hz, 2H, CH₂), 3.40-3.47 (m, 4H, ArCH₂Ar), 3.34 (d, J = 12.3 Hz, 2H, NCH₂), 4.03-4.09 (m, 4H, ArCH₂Ar), 4.37-4.43 (m, 2H, NCHCO + OCH), 4.59 (s, 1H, NH), 6.98-7.22 (m, 8H, ArH). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 31.4, 31.7, 32.6, 34.1, 34.3, 36.4, 51.0, 60.5, 84.1, 125.2, 126.1, 126.5, 128.2, 128.4, 130.2, 130.4, 133.6, 133.8, 143.0, 146.4, 148.3, 148.6, 148.9, 150.8, 171.8. IR (KBr): 3440, 2959, 2869, 1629, 1485, 1364, 1299, 1262, 1204, 1031, 909, 874, 802 cm^-¹. Anal. Calcd for C₄₉H₆₃NO₆: C, 77.23; H, 8.33; N, 1.84. Found: C, 77.52; H, 8.06; N, 1.65. ESI-MS: m/z (%) = 762 (8) [M + 1]⁺, 784 (100) [M + Na]⁺.

20

Analytical data for compound 2: Yield: 78%. White solid, mp 261-263 ˚C. [α]_D ^²6 +43.0 (c = 1.0, CHCl₃). ^¹H NMR (300 MHz, CD₃OD): δ = 1.07 [s, 18H, 2 × C(CH₃)₃], 1.24 [s, 18H, 2 × C(CH₃)₃], 2.72 (m, 2H, CH₂), 2.84-2.90 (m, 2H, CH₂), 3.35-3.48 (m, 4H, ArCH₂Ar), 3.68-3.74 (m, 2H, NCH₂), 4.17-4.38 (m, 8H, NCH₂ + ArCH₂Ar + OCH), 4.65-4.69 (m, 2H, NCHCO), 5.08 (s, 2H, NH), 7.05-7.16 (m, 8H, ArH). ^¹³C NMR (75 MHz, CDCl₃): δ = 30.8, 31.5, 33.7, 51.2, 60.0, 85.1, 124.8, 124.9, 125.5, 125.9, 127.9, 128.0, 128.5, 131.0, 131.1, 131.7, 141.9, 146.5, 149.9, 173.6, 173.7. IR (KBr): 3448, 2961, 2868, 1632, 1485, 1393, 1362, 1300, 1203, 1124, 1035, 979, 873 cm^-¹. Anal. Calcd for C₅₄H₇₀N₂O₈: C, 74.11; H, 8.06; N, 3.20. Found: C, 74.32; H, 7.86; N, 3.45. ESI-MS: m/z (%) = 898 (100) [M + Na]⁺.

21

Analytical data for compound 3: Yield: 96%. White solid, mp 137-139 ˚C. [α]_D ^²7 -6.7 (c = 8.5, CHCl₃). ^¹H NMR (300 MHz, CDCl₃): δ = 0.82 [s, 9H, C(CH₃)₃], 0.94 [s, 9H, C(CH₃)₃], 1.06 (t, J = 7.2 Hz, 3H, CH₃), 1.25 [s, 9H, C(CH₃)₃], 1.31 [s, 9H, C(CH₃)₃], 1.58-1.72 (m, 2H, CH₂), 1.81-1.98 (m, 2H, CH₂), 2.43-2.52 (m, 1H, CH₂), 2.65-2.82 (m, 1H, CH₂), 3.21-3.34 (m, 4H, ArCH₂Ar), 3.58 (br s, 2H, ArOCH₂), 3.91-3.96 (m, 2H, NCH₂), 4.01-4.28 (m, 4H, ArCH₂Ar), 4.39-4.51 (m, 2H, OCH + NCHCOO), 6.53-6.81 (m, 4H, ArH), 6.98-7.06 (m, 4H, ArH). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.0, 19.3, 33.7, 33.8, 34.9, 59.7, 84.0, 124.8, 125.1, 125.3, 125.7, 125.8, 127.0, 127.3, 128.2, 128.4, 131.5, 132.1, 132.2, 141.4, 146.3, 146.8, 149.3, 149.4, 150.2, 173.1. IR (KBr): 3441, 2960, 2870, 1717, 1635, 1485, 1392, 1362, 1300, 1201, 1123, 1026, 872 cm^-¹. Anal. Calcd for C₅₃H₇₁NO₆: C, 77.81; H, 8.75; N, 1.71. Found: C, 77.42; H, 8.96; N, 1.45. ESI-MS: m/z (%) = 818 (23) [M + 1]⁺, 840 (100) [M + Na]⁺.

22

Analytical data for compound 4: Yield: 75%. White solid, mp 157-159 ˚C. [α]_D ^²7 -31.3 (c = 1.0, CHCl₃). ^¹H NMR (300 MHz, CDCl₃): δ = 0.84 [s, 9H, C(CH₃)₃], 0.87 [s, 9H, C(CH₃)₃], 0.91 (t, J = 7.2 Hz, 3H, CH₃), 1.27 [s, 9H, C(CH₃)₃], 1.29-1.31 (m, 5H, CH₂), 1.32 [s, 9H, C(CH₃)₃], 1.46-1.51 (m, 2H, CH₂), 1.60-1.65 (m, 1H, CH₂), 1.80-1.94 (m, 2H, CH₂), 2.33 (t, J = 7.5 Hz, 2H, OOCCH₂), 2.71-2.93 (m, 2H, CH₂), 3.23-3.39 (m, 4H, ArCH₂Ar), 3.76 (d, J = 13.5 Hz, 2H, NCH₂), 3.99-4.16 (m, 4H, ArCH₂Ar), 4.01-4.48 (m, 2H, OCH + NCHCOO), 5.50 (s, 1H, OH), 5.63 (s, 1H, OH), 6.57-7.08 (m, 8H, ArH). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.1, 22.5, 24.9, 29.0, 29.1, 30.7, 30.8, 31.3, 31.4, 31.6, 33.8, 35.5, 49.0, 59.9, 84.3, 124.8, 125.0, 125.3, 126.0, 126.9, 127.3, 127.6, 127.7, 129.0, 130.7, 131.0, 131.4, 132.0, 141.8, 142.0, 142.2, 147.0, 148.0, 148.3, 149.7, 149.9, 172.0, 173.3, 178.0. IR (KBr): 3520, 2957, 2868, 1761, 1634, 1485, 1363, 1301, 1204, 1139, 1122, 1037, 873 cm^-¹. Anal. Calcd for C₅₇H₇₇NO₇: C, 77.08; H, 8.74; N, 1.58. Found: C, 77.34; H, 8.46; N, 1.35. ESI-MS: m/z (%) = 888 (26) [M + 1]⁺, 910 (100) [M + Na]⁺.

23

General procedure for asymmetric aldol reactions: Catalyst 1 (2 mol%) was added to a suspension of aldehyde (1.0 mmol) and ketone (3.0 mmol) in water (324 µL, 18 mmol) at room temperature. The mixture was allowed to stir for the given time, then ethyl acetate (10 mL) and anhydrous MgSO₄ (0.6 g) were added. After filtration, the solvent was evaporated under vacuum and the crude products were purified by flash chromatography (hexane-EtOAc). The anti/syn ratio (diastereoselectivity) and enantiomeric excess (enantioselectivity) were determined by chiral HPLC analysis (see ref 24).

24

Compound 7a: Yield: 73%; Ratio anti/syn = 90:10. HPLC conditions: Daicel Chiralpak AD-H column; i-PrOH-Hexane, 5:95; flow rate 1.0 mL/min; λ = 254 nm; 20 ˚C. anti-Diastereomer: t _R(major) = 60.2 min and t _R(minor) = 43.5 min; 98% ee. For further data on 7 and HPLC spectra, see Supporting Information.