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Synlett 2008(4): 535-538  
DOI: 10.1055/s-2008-1032083
LETTER
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Tandem Diels-Alder Macrocyclizations Starting from Sorbyl or Sorboyl Derivatives

Klaus Banert*, Patrick Schumann
Organic Chemistry, Chemnitz University of Technology, Straße der Nationen 62, 09107 Chemnitz, Germany
Fax: +49(371)53121229; e-Mail: klaus.banert@chemie.tu-chemnitz.de;
Further Information

Publication History

Received 26 November 2007
Publication Date:
12 February 2008 (online)

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Abstract

A novel class of diastereomeric macrocycles was synthesized via tandem Diels-Alder reactions of prochiral double sorbyl or sorboyl derivatives and short-bridged bis-1,2,4-triazoline-3,5-diones.

Key words

diastereoselectivity - Diels-Alder - macrocycles - sorbyl and sorboyl derivatives - 1,2,4-triazoline-3,5-dione

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General Procedure for Macrocyclizations
A flask is charged with CH2Cl2 (800-1400 ml) as a diluting agent. Dichloromethane often contains 2-methylbut-2-ene as a stabilizer which undergoes ene reaction when it is treated with TAD derivatives. Therefore, it must be removed before using larger amounts of CH2Cl2, e.g. by the addition of a few drops of bromine. Furthermore, the flask is equipped with two dropping funnels containing 15-50 mM solutions of bis-TAD 2 and bisdiene 1. Both solutions are simultaneously added dropwise at r.t. into the vigorously stirred solvent at such a rate that only a faint pink color can be observed (normally 3-5 h). After complete addition, the reaction mixture is concentrated in vacuo and chromatographed on silica gel to yield colorless solids.
Spectroscopic Data of rac -3ac, rac -3ad, and meso -3ad
rac-3ac (both enantiomers): mp 168 °C (dec.) (CHCl3). IR (CCl4): ν = 2254 (w, CºN), 1765 (m), 1710 (vs, C=O) cm-1. 1H NMR (400 MHz, CDCl3, CHCl3 = 7.26 ppm): δ = 5.99 (ddd, 3 J = 10.4 Hz, J = 5.6, 2.4 Hz, 2 H, =CHCHMe), 5.70 (ddd, J = 10.4 Hz, 3 J = 2.4 Hz, J = 1.6 Hz, 2 H, =CHCHCH2), 4.48 (m, 2 H, CHCH2), 4.21 (q, 3 J = 6.8 Hz, 2 H, CHMe), 3.89 (AA′BB′ spin system, 2 H, NCH 2CH 2N), 3.71 (AA′BB′ spin system, 2 H, NCH 2CH 2N), 3.32 [dd, ï2 Jï = 15.6 Hz, 3 J = 3.6 Hz, 2 H, CH 2C(CN)2CH 2], 2.32 [dd, ï2 Jï = 15.6 Hz, 3 J = 2.8 Hz, 2 H, CH 2C(CN)2CH 2], 1.67 (d, 3 J = 6.8 Hz, 6 H, Me). 13C NMR (100 MHz, CDCl3 = 77.00 ppm): δ = 155.0 (s, NC=O), 151.3 (s, NC=O), 128.5 (d), 124.0 (d), 114.5 (s, CN), 48.3 (d), 53.3 (d), 40.0 (t), 37.4 (t), 33.7 [s, C(CN)2], 20.4 (q). ESI-HRMS: m/z [M + K]+ calcd for C21H22N8O4: 489.1396; found: 489.1387. Anal. Calcd for C21H22N8O4·CHCl3: C, 46.37; H, 4.07; N, 19.66. Found: C, 46.65; H, 3.96; N, 19.70.
rac-3ad (both enantiomers): mp 76 °C (CH2Cl2-acetone). IR (CDCl3): ν = 1764 (s), 1710 (vs, C=O) cm-1. 1H NMR (400 MHz, CDCl3, CHCl3 = 7.26 ppm): δ = 5.88 (ddd, 3 J = 10.4 Hz, J = 4.4, 2.0 Hz, 2 H, =CH), 5.67 (br d, J = 10.4 Hz, 2 H, =CH), 4.46-4.20 (m, 4 H, OCH2 and CHMe), 4.43 (m, 2 H, CHCH2O), 3.99 (AA′BB′ spin system, 2 H, NCH 2CH 2N), 3.62 (AA′BB′ spin system, 2 H, NCH 2CH 2N), 3.52 (br d, ï2 Jï = 9.2 Hz, 2 H, CH2O), 3.40 (br d, ï2 Jï = 8.6 Hz, 2 H, CH2O), 2.93 (br d, ï2 Jï = 8.6 Hz, 2 H, CH2O), 1.42 (d, 3 J = 6.4 Hz, 6 H, CHMe), 0.80 (s, 6 H, CMe2). 13C NMR (100 MHz, CDCl3 = 77.00 ppm): δ = 153.8 (br s, NCO), 151.5 (s, NCO), 127.3 (d), 123.4 (d), 76.3 (t, OCH2), 70.1 (t, OCH2), 55.9 (d), 49.3 (d), 36.8 (br t, NCH2), 36.3 (s, CMe2), 22.3 (q, CMe 2), 18.2 (q, CHMe). ESI-HRMS: m/z [M + K]+ calcd for C23H32N6O6: 527.2015; found: 527.1997. Anal. Calcd for C23H32N6O6: C, 56.55; H, 6.60; N, 17.20. Found: C, 56.38; H, 6.45; N, 17.11.
Compound meso-3ad: mp 69 °C (CH2Cl2-acetone). IR (CDCl3): ν = 1763 (s), 1707 (vs, C=O) cm-1. 1H NMR (400 MHz, CDCl3, CHCl3 = 7.26 ppm): δ = 5.89 (ddd, 3 J = 10.4 Hz, J = 4.4, 2.0 Hz, 2 H, =CH), 5.81 (ddd, 3 J = 10.4 Hz, J = 2.0, 1.6 Hz, 2 H, =CH), 4.52 (qd, 3 J = 6.4 Hz, J = 1.6 Hz, 2 H, CHMe), 4.19 (m, 2 H, CHCH2O), 3.92 (dd, J = 10.0, 6.0 Hz, 2 H, CHCH 2O), 3.76-3.85 (m, 6 H, therein AA′BB′ spin system, 4 H, NCH2 and CHCH 2 O), 3.41 (br d, ï2 Jï = 9.0 Hz, 2 H, CH2O), 3.16 (br d, ï2 Jï = 9.0 Hz, 2 H, CH2O), 1.38 (d, 3 J = 6.4 Hz, 6 H, CHMe), 0.85 (s, 3 H, CMe 2), 0.81 (s, 3 H, CMe 2). 13C NMR (100 MHz, CDCl3 = 77.00 ppm): δ = 155.5 (br s, NCO). 150.9 (s, NCO), 126.9 (d), 123.8 (d), 76.5 (t, OCH2), 71.4 (br t, OCH2), 48.7 (d), 56.0 (d), 37.6 (t, NCH2), 36.6 (s, CMe2), 22.2 (q, CMe 2), 21.9 (q, CMe 2), 18.3 (q, CHMe). ESI-HRMS: m/z [M + K]+ calcd for C23H32N6O6: 527.2015; found: 527.2005. Anal. Calcd for C23H32N6O6: C, 56.55; H, 6.60; N, 17.20. Found: C, 56.52; H, 6.54; N, 17.18.

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A diluted solution of 1g (1 equiv) in CH2Cl2 was treated with 4-phenyl-1,2,4-triazoline-3,5-dione (0.8 equiv) in CH2Cl2 at r.t. After evaporation of the solvent, NMR analysis of the crude product revealed only a mixture of 1g and the PTAD-sorbyl adduct, which was isolated by flash chromatography in 69% yield as a colorless solid.
[(5S,8S)-8-Methyl-1,3-dioxo-2-phenyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]methyl (2E,4E)-hexa-2,4-dienoate (both enantiomers): mp (CH2Cl2-acetone): 117 °C. IR (CDCl3): ν = 1770 (w), 1712 (vs, C=O), 1426 (m), 1243 (m) cm-1. 1H NMR (400 MHz, CDCl3, CHCl3 = 7.26 ppm): δ = 7.52 (m, 2 H, 3-PhCH), 7.46 (m, 2 H, 2-PhCH), 7.36 (tt, J = 7.2, 1.2 Hz, 1 H, 4-PhCH), 7.25 (dd, J = 15.2, 10.8 Hz, 1 H, =CH), 6.04-6.20 (m, 2 H, =CH), 5.92 (ddd, J = 10.8, 3.2, 1.6 Hz, 1 H, =CH), 5.76 (ddd, J = 10.8, 4.0, 2.0 Hz, 1 H, =CH), 5.23 (dd, J = 15.6, 0.4 Hz, 1 H, =CHCO2), 4.74 (m, 1 H, CHCH2O), 4.65 (dd, ï2 Jï = 11.6 Hz, J = 4.0 Hz, 1 H, CH2O), 4.43-4.50 (m therein dd at 4.48 ppm, ï2 Jï = 11.6 Hz, J = 4.8 Hz, 2 H, CH2O and CHMe), 1.83 (d, J = 6.0 Hz, 3 H, =CHMe), 1.55 (d, J = 6.8 Hz, 3 H, CHMe). 13C NMR (100 MHz, CDCl3 = 77.00 ppm): δ = 166.6 (s, CO2), 152.3 (s, NCO), 151.3 (s, NCO), 146.2 (d), 140.2 (d), 131.1 (s, i-Ph), 129.7 (d), 129.6 (d), 129.0 (d), 128.0 (d), 125.6 (d), 120.9 (d), 117.8 (d), 62.4 (t, OCH2), 53.0 (d, chiral center), 51.0 (d, chiral center), 19.4 (q), 18.7 (q). Anal. Calcd for C20H21N3O4: C, 65.38; H, 5.76; N, 11.44. Found: C, 65.18; H, 5.94; N, 11.41.