The Use of Sodium Chlorite in the Direct Synthesis of Glycidic Amides: 
Enantiopure Synthesis of Both Enantiomers of Norbalasubramide

Lilia Fuentes; Mireya Hernández-Juarez; Joel L. Terán; Leticia Quintero; Fernando Sartillo-Piscil

doi:10.1055/s-0032-1316893

Synlett, Table of Contents

Synlett 2013; 24(7): 878-882
DOI: 10.1055/s-0032-1316893

letter

The Use of Sodium Chlorite in the Direct Synthesis of Glycidic Amides: Enantiopure Synthesis of Both Enantiomers of Norbalasubramide

Lilia Fuentes

Centro de Investigación de la Facultad de Ciencias Químicas y Centro de Química del ICUAP, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, San Manuel 72570, Puebla, México Fax: +52(222)2454972 Email: fernando.sartillo@correo.buap.mx

,

Mireya Hernández-Juarez

Centro de Investigación de la Facultad de Ciencias Químicas y Centro de Química del ICUAP, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, San Manuel 72570, Puebla, México Fax: +52(222)2454972 Email: fernando.sartillo@correo.buap.mx

,

Joel L. Terán

Centro de Investigación de la Facultad de Ciencias Químicas y Centro de Química del ICUAP, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, San Manuel 72570, Puebla, México Fax: +52(222)2454972 Email: fernando.sartillo@correo.buap.mx

,

Leticia Quintero*

Centro de Investigación de la Facultad de Ciencias Químicas y Centro de Química del ICUAP, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, San Manuel 72570, Puebla, México Fax: +52(222)2454972 Email: fernando.sartillo@correo.buap.mx

,

Fernando Sartillo-Piscil*

Centro de Investigación de la Facultad de Ciencias Químicas y Centro de Química del ICUAP, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, San Manuel 72570, Puebla, México Fax: +52(222)2454972 Email: fernando.sartillo@correo.buap.mx

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Abstract

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Abstract

Recently, the first direct method for preparing 2,3-epoxyamides (glycidic amides) was disclosed. Now in this letter, the enantiopure synthesis of both enantiomers of norbalasubramide featuring this synthetic method is reported. To this end, chiral N-allyltryptamine 12 was prepared and transformed into an inseparable mixture of diastereomeric epoxyamides 13a/13b, which were submitted to intramolecular cyclization with Cu(OTf)₂ to afford a separable mixture of eight-membered ring lactams 14a and 14b. Finally, after removal of the protective group and the chiral auxiliary an enantiopure synthesis of the title compounds was completed.

Key words

2,3-epoxyamides - glycidic amides - tandem oxidation - sodium chlorite - balasubramide - norbalasubramide

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References

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11 General Procedure for the Tandem Oxidation of Allyamines; tert-Butyl-3-[2-{3-phenyl-N-[(S)-1-phenylethyl]oxirane-2-carboxamido}ethyl]-1H-indole-1-carboxylate (13a/13b): Allylamine 12 (4.00 g, 8.32 mmol) and NaH₂PO₄·2H₂O (12.98 g, 83.22 mmol) were dissolved in a mixture of t-BuOH–THF–H₂O (7:3:3; 108 mL), the reaction mixture was then stirred vigorously at r.t. for 15 min after which time the solution was cooled to 0 °C followed by the addition of 2-methylbut-2-ene (58.37 g, 832.22 mmol) and the sequential addition of NaClO₂ (6.02 g, 66.58 mmol) dissolved in H₂O (10 mL). The reaction mixture was stirred for 8 h, then phases were separated and the aqueous phase was extracted with EtOAc (3 × 25 mL). The combined organic phases were dried over Na₂SO₄ and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel to give an inseparable mixture of diastereomeric epoxyamides 13a and 13b in a 50:50 ratio as a pale yellow oil (2.97 g, 70%); [α]_D ²⁰ –23.9 (c = 1.0, CH₂Cl₂). NMR data is reported as a mixture of diastereoisomers and E/Z rotamers. ¹H NMR (400 MHz, CDCl₃): δ = 1.60 (d, J = 6.8 Hz), 1.64 (s), 1.66 (d, J = 6.4 Hz), 2.30–2.41 (m), 2.56–2.64 (m), 2.70–2.78 (m), 2.87–2.99 (m), 3.23–3.35 (m), 3.38–3.61 (m), 3.66 (dd, J = 3.6, 1.6 Hz), 3.79 (dd, J = 6.0, 2.0 Hz), 4.19 (ddd, J = 20.8, 11.6, 1.6 Hz), 5.33 (q, J = 6.8 Hz), 5.39 (q, J = 6.8 Hz), 6.13 (app quint., J = 7.2 Hz), 6.75 (d, J = 7.8 Hz), 6.88–7.03 (m), 7.18–7.45 (m), 8.04 (br). ¹³C NMR (100 MHz, CDCl₃): δ = 16.5, 18.3, 18.5, 23.9, 24.2, 26.7, 26.8, 28.1, 28.1, 43.4, 43.5, 44.0, 44.0, 51.8, 51.9, 54.7, 54.9, 57.4, 57.5, 57.9, 58.0, 58.1, 58.3, 83.3, 83.6, 115.0, 115.2, 115.3, 116.4, 117.9, 118.2, 119.3, 119.3, 122.4, 122.4, 123.0, 123.0, 123.1, 124.3, 124.4, 125.5, 125.6, 126.7, 127.1, 127.8, 127.9, 127.9, 128.0, 128.1, 128.6, 128.7, 128.8, 129.6, 130.3, 135.2, 135.3, 135.4, 139.2, 139.8, 140.0, 149.4, 149.7, 166.5, 166.6, 166.7. HRMS (FAB): m/z [M + H]⁺ calcd for C₃₂H₃₅N₂O₄: 511.2597; found: 511.2550.
12 General Procedure for the Intramolecular Ring Opening: To a solution of 13a/13b (2.00 g, 3.91 mmol) in anhyd MeCN (45 mL) at r.t. was added Cu(OTf)₂ (0.28 g, 0.78 mmol) dissolved in anhyd MeCN (5 mL). The reaction mixture was stirred for 30 min before H₂O (15 mL) was added. The phases were separated and the aqueous phase was extracted with EtOAc (3 × 25 mL). The organic phase was dried over Na₂SO₄, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel or recrystallized with EtOAc–hexane to give 14a (0.80 g, 40%) and 14b (0.84 g, 42%). (5S,6R)-tert-Butyl-5-hydroxy-4-oxo-6-phenyl-3-[(S)-1-phenylethyl]-3,4,5,6-tetrahydro-1H-azocino[5,4-b]indole-7(2H)-carboxylate (14a): Obtained as a white solid (0.80 g, 40%); mp 185–186 °C; [α]_D ²⁰ –32.6 (c = 1.0, CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 1.45 (d, J = 6.8 Hz, 3 H), 1.53 (s, 9 H), 2.98–3.15 (m, 2 H), 3.30 (dt, J = 14.0, 9.6 Hz, 1 H), 3.60 (dd, J = 14.0, 9.6 Hz, 1 H), 3.97 (d, J = 9.2 Hz, 1 H), 4.89 (t, J = 9.6 Hz, 1 H), 5.29 (d, J = 9.6 Hz, 1 H), 5.98 (q, J = 6.8 Hz, 1 H), 6.51–6.60 (m, 3 H), 6.74–6.77 (m, 2 H), 6.96–7.00 (m, 1 H), 7.18–7.30 (m, 7 H), 7.98 (d, J = 8.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 15.9, 23.0, 28.0, 39.5, 51.6, 51.9, 73.1, 84.2, 114.4, 115.5, 117.3, 122.5, 123.8, 126.8, 126.9, 127.0, 127.6, 128.0, 128.7, 129.1, 136.0, 136.5, 138.0, 139.6, 149.9, 174.8. HRMS (FAB): m/z [M + H]⁺ calcd for C₃₂H₃₅N₂O₄: 526.2597; found: 511.2613. (5R,6S)-tert-Butyl-5-hydroxy-4-oxo-6-phenyl-3-[(S)-1-phenylethyl]-3,4,5,6-tetrahydro-1H-azocino[5,4-b]indole-7(2H)-carboxylate (14b): Obtained as a pale yellow oil (0.84 g, 42%); [α]_D ²⁰ +17.6 (c = 1.0, CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 0.68 (d, J = 6.8 Hz, 3 H), 1.51 (s, 9 H), 2.92–3.43 (m, 4 H), 3.92 (d, J = 9.6 Hz, 1 H), 4.85 (t, J = 9.6 Hz, 1 H), 5.28 (d, J = 9.2 Hz, 1 H), 5.84 (q, J = 6.8 Hz, 1 H), 6.99–7.58 (m, 13 H), 7.94–8.19 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 15.3, 23.1, 28.0, 40.6, 51.4, 51.4, 73.1, 84.4, 114.6, 116.0, 117.2, 122.6, 124.2, 126.8, 127.2, 127.4, 128.1, 128.4, 128.5, 129.1, 136.0, 137.1, 139.5, 140.0, 149.8, 174.6. HRMS (FAB): m/z [M + H]⁺ calcd for C₃₂H₃₅N₂O₄: 526.2597; found: 511.2610.
13 Jacquemard U, Béneteau V, Lefoix M, Routier S, Mérour J.-Y, Coudert G. Tetrahedron 2004; 60: 10039
14 N-Boc Deprotection: To a solution of lactam 14a (0.40 g, 0.78 mmol) in anhyd THF (2 mL) at r.t. was added TBAF (7.83 mmol, 1.0 M solution). The reaction mixture was refluxed for 5 h. Then, the mixture was cooled to r.t., H₂O was added (5 mL), the phases were separated and the aqueous phase was extracted with EtOAc (2 × 15 mL). The combined organic phases were dried over Na₂SO₄ and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel, and then recrystallized in CH₂Cl₂–hexane to give the corresponding product. (5S,6R)-5-Hydroxy-6-phenyl-3-[(S)-1-phenylethyl]-2,3,5,6-tetrahydro-1H-azocino[5,4-b]indol-4(7H)-one (15a): obtained as a white solid (0.25 g, 79%); mp 231–267 °C (decomp.); [α]_D ²⁰ –7.1 (c = 1.0, CH₂Cl₂). The NMR data is reported as a mixture of rotamers. ¹H NMR (400 MHz, CDCl₃): δ = 1.47 (d, J = 7.2 Hz), 1. 57 (d, J = 7.2 Hz), 1.99 (br), 2.95 (ddd, J = 16.0, 9.6, 4.0 Hz), 3.11 (dt, J = 16.0, 8.4 Hz), 3.39 (ddd, J = 14.4, 9.6, 8.0 Hz), 3.69 (ddd, J = 14.8, 8.8, 4.0 Hz), 4.28 (d, J = 9.6 Hz), 4.98 (d, J = 9.6 Hz), 5.88 (q, J = 7.2 Hz), 5.94 (q, J = 7.2 Hz), 6.34 (s), 6.53–6.59 (m), 6.82–6.91 (m), 7.04–7.08 (m), 7.15–7.34 (m), 8.40 (br), 8.55 (br). ¹³C NMR (100 MHz, CDCl₃): δ =16.0, 23.1, 40.3, 42.6, 51.2, 52.4, 53.0, 72.3, 106.5, 110.2, 110.3, 110.7, 117.7, 118.6, 119.0, 121.5, 122.6, 122.9, 127.0, 127.0, 127.2, 127.5, 127.7, 127.8, 128.2, 128.4, 128.4, 128.5, 128.8, 133.8, 134.0, 135.4, 135.5, 135.7, 138.0, 138.2, 139.4, 139.8, 140.2, 169.9, 174.9. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₇H₂₇N₂O₂: 411.2073; found: 411.2060. (5R,6S)-5-Hydroxy-6-phenyl-3-[(S)-1-phenylethyl]-2,3,5,6-tetrahydro-1H-azocino[5,4-b]indol-4(7H)-one (15b): obtained as a white solid (0.38 g, 80%); mp 147–150 °C; [α]_D ²⁰ –1.2 (c = 1.0, CH₂Cl₂). The NMR data is reported as a mixture of rotamers. ¹H NMR (400 MHz, CDCl₃): δ = 0.78 (d, J = 6.8 Hz), 1.59 (d, J = 7.2 Hz), 3.03–3.20 (m), 3.20–3.30 (m), 3.39–3.53 (m), 3.87 (d, J = 8.8 Hz), 4.27 (d, J = 8.8 Hz), 4.95 (t, J = 8.8 Hz, 1 H), 5.83 (q, J = 6.8 Hz, 1 H), 5.99 (q, J = 6.8 Hz), 7.13–7.36 (m), 7.51–7.54 (m), 8.02 (s), 8.20 (s). ¹³C NMR (100 MHz, CDCl₃): δ = 15.6, 23.4, 41.0, 41.3, 51.6, 51.9, 53.5, 72.3, 106.8, 110.7, 110.8, 117.3, 118.7, 119.2, 119.4, 119.5, 121.9, 123.0, 127.3, 127.4, 127.5, 127.5, 127.8, 128.3, 128.5, 128.6, 128.9, 132.9, 134.3, 135.3, 135.7, 137.9, 139.4, 139.9, 140.0, 169.6, 174.7. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₇H₂₇N₂O₂: 411.2073; found: 411.2079.
15 Birch Debenzylation: A solution of 15b (0.26 g, 0.63 mmol) in anhyd THF (2 mL) was added dropwise to a deep blue solution of Li (0.030 g, 4.38 mmol) in condensed NH₃ (ca. 5 mL) at –78 °C. The reaction mixture was allowed to stir for 3 h at –78 °C before H₂O (3 mL) was added. The mixture was extracted with EtOAc, dried with Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, and recrystallized in CH₂Cl₂–hexane to afford the corresponding product. (–)-Norbalasubramide: obtained as a white solid (0.15 g, 79%); mp 251–255 °C (decomp.); [α]_D ²⁰ –2.9 (c = 0.2, CHCl₃); [α]_D ²⁰ –3.8 (c = 0.5, MeOH), {[α]_D ²⁰ –2.5 (c = 0.2, CHCl₃); see ref. 16}. ¹H NMR (400 MHz, CDCl₃): δ = 3.19–3.40 (m, 4 H), 3.60–3.71 (m, 1 H), 4.20 (d, J = 9.2 Hz, 1 H), 4.88 (d, J = 9.2 Hz, 1 H), 7.10 (ddd, J = 8.8, 7.2, 1.6 Hz, 2 H), 7.20–7.41 (m, 6 H), 7.44–7.63 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 23.8, 40.1, 52.6, 71.9, 106.2, 110.8, 117.2, 119.0, 121.6, 127.2, 128.1, 128.3, 128.5, 134.2, 135.5, 140.0, 176.9. (+)-Norbalasubramide: obtained as a white solid (0.14 g, 76%); mp 251–255 °C (decomp.); [α]_D ²⁰ +3.7 (c = 0.5, MeOH).
16 Zheng C, Li Y, Yang Y, Wang H, Cui H, Zhang J, Zhao G. Adv. Synth. Catal. 2009; 351: 1685

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