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Synlett 2013; 24(5): 630-634
DOI: 10.1055/s-0032-1318301
letter
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Preparation of New N,N-Dialkyl-2-amino-1,1,2-triphenylethanol Catalysts and a Kinetic Resolution in the Addition of Diethylzinc to Flavene-3-carbaldehydes

Seock Yong Kang
Department of Chemistry and KFnSC, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea   Fax: +82(2)34365382   eMail: parkyong@konkuk.ac.kr
,
Jinho Baek
Department of Chemistry and KFnSC, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea   Fax: +82(2)34365382   eMail: parkyong@konkuk.ac.kr
,
Yi Kyung Ko
Department of Chemistry and KFnSC, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea   Fax: +82(2)34365382   eMail: parkyong@konkuk.ac.kr
,
Chan Im
Department of Chemistry and KFnSC, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea   Fax: +82(2)34365382   eMail: parkyong@konkuk.ac.kr
,
Yong Sun Park*
Department of Chemistry and KFnSC, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea   Fax: +82(2)34365382   eMail: parkyong@konkuk.ac.kr
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Publikationsverlauf

Received: 18. Dezember 2012

Accepted after revision: 01. Februar 2013

Publikationsdatum:
25. Februar 2013 (online)

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Abstract

Enantiopure N,N-dialkyl-(S)-2-amino-1,1,2-triphenyl­ethanols were prepared using a new synthetic methodology and tested for their ability to catalyze the enantioselective addition of diethylzinc to aldehydes. The structural modification of N-substituents of the catalysts led us to identify N-methyl-N-(S)-1-phenyl­ethyl-substituted 4d as an effective catalyst for the addition. Also disclosed is a kinetic resolution of racemic flavene-3-carbaldehydes with the chiral catalyst.

Key words

addition - asymmetric catalysis - chirality - enantioselectivity - kinetic resolution

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett. Included are detailed experimental procedures and characterization data (NMR spectra and HPLC chromatogram).
  • Supporting Information
 

  • References and Notes

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  • 6 Preparation of Chiral Catalyst 4d To a solution of 1:1 diastereomeric mixture of 2-bromo-2-phenylacetic acid (R)-pantolactone ester 2 in dry CH2Cl2 (0.1 M) at r.t. was added (S)-1-phenylethylamine (1.2 equiv), TBAI (1.0 equiv), and DIPEA (1.0 equiv). After the resulting reaction mixture was stirred at r.t. for 12 h, the solvent was evaporated, and the crude material was purified by column chromatography on silica gel to give 3d in 71% yield with 99:1 dr. To a solution of 3d in DMF at r.t., MeI (2.0 equiv) and DIPEA (1.2 equiv) were added slowly. The resulting reaction mixture was stirred at r.t. for 24 h. After the mixture was concentrated, the crude product was dissolved in anhyd THF. To the solution of the product was added a solution of PhMgBr (4.0 equiv). The reaction was then allowed to proceed at r.t. for 24 h. The reaction was quenched by the addition of 1 M aq HCl and extracted with EtOAc. The combined organic extracts were dried with anhyd MgSO4, filtered, and concentrated in vacuo. Chromatographic separation on silica gel afforded the chiral catalyst 4d with 41% yield. 1H NMR (400 MHz, CDCl3): δ = 7.25–6.87 (m, 20 H), 5.68 (s, 1 H), 4.98 (s, 1 H), 3.49 (q, J = 6.8 Hz, 1 H), 1.88 (s, 3 H), 1.15 (d, J = 6.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 149.7, 146.1, 142.6, 138.4, 131.0, 128.2, 128.1, 127.9, 127.5, 127.3, 127.0, 126.8, 126.4, 126.3, 125.4, 125.3, 79.1, 74.0, 59.8, 35.3, 15.5. HRMS: m/z calcd for C29H30NO [M+ + 1]: 408.2327; found: 408.2329.
  • 7 General Procedure for the Addition of Diethylzinc to Aldehydes Diethylzinc (1.0 M in toluene, 2.0 equiv) was added to a solution of chiral catalyst (0.05 equiv) and aldehyde (1.0 equiv) in t-BuOMe at 0 °C. The homogeneous solution was stirred at r.t. for 5 h (3 h for kinetic resolution). The reaction was quenched by addition of 1 M aq HCl and extracted with CHCl3. The combined organic extracts were dried with anhyd MgSO4, filtered, and concentrated in vacuo. Chromatographic separation on silica gel (eluent hexane–EtOAc) afforded the enantioenriched ethanols, and the enantioselectivity of the products was measured by HPLC with chiral columns using racemic material as a standard (eluent: i-PrOH in hexane; 0.5 mL/min, 217 nm UV detector)

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  • 12 The selectivity factor (s) was estimated using the equation, s = kS/kR = ln[(1 – C)(1 – ee)]/ln[(1 – C)(1 + ee)], where ee is the enantiomeric excess of unconverted aldehyde 5 and the conversion (C) determined by 1H NMR of reaction mixture.
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