Synthesis of Functionalized Δ3-Pyrrolines via a Ag(I)-Catalyzed Cyclization of Amino Acid Derived Allenes

Branko Mitasev; Kay M. Brummond

doi:10.1055/s-2006-949624

LETTER

Synthesis of Functionalized Δ³-Pyrrolines via a Ag(I)-Catalyzed Cyclization of Amino Acid Derived Allenes

Branko Mitasev, Kay M. Brummond*
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Fax: +1(412)6248611; e-Mail: kbrummon@pitt.edu;

Abstract

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Abstract

Diversity-oriented synthesis (DOS) of a collection of novel, highly functionalized Δ³-pyrrolines has been accomplished by a AgNO₃-catalyzed cyclization reaction of allenic amino acids that proceeds with transfer of chiral information. A new mode of cyclization of allenic benzoyl-protected amines in the Ag(I)-catalyzed reaction leading to oxazines was observed.

Key words

pyrrolines - allene - cyclization - silver catalysis - amino acid - oxazine

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References

References and Notes

<A NAME="RS09206ST-1A">1a</A> Burke MD. Schreiber SL. Angew. Chem. Int. Ed. 2004, 43: 46

<A NAME="RS09206ST-1B">1b</A> Schreiber SL. Science 2000, 287: 1964

<A NAME="RS09206ST-1C">1c</A> Beeler AB. Schaus SE. Porco JA. Curr. Opin. Chem. Biol. 2005, 9: 277

<A NAME="RS09206ST-1D">1d</A> Tan DS. Nat. Chem. Biol. 2005, 1: 74

<A NAME="RS09206ST-2A">2a</A> Brummond KM. Mitasev B. Org. Lett. 2004, 6: 2245

<A NAME="RS09206ST-2B">2b</A> Brummond KM. Chen HF. Mitasev B. Casarez AD. Org. Lett. 2004, 6: 2161

<A NAME="RS09206ST-2C">2c</A> Brummond KM. Curran DP. Mitasev B. Fischer S. J. Org. Chem. 2005, 70: 1745

<A NAME="RS09206ST-3">3</A> Brummond KM. Chen D. Org. Lett. 2005, 7: 3473

<A NAME="RS09206ST-4A">4a</A> O’Hagen D. Nat. Prod. Rep. 2000, 17: 435

<A NAME="RS09206ST-4B">4b</A> Dohty P. Dickson JG. Flanigan TP. Walsh FS. J. Neurochem. 1985, 44: 1259

<A NAME="RS09206ST-4C">4c</A> Anderson WK. Milowsky AS. J. Med. Chem. 1987, 30: 2144

<A NAME="RS09206ST-4D">4d</A> Johnson JH. Phillipson DW. Kahle AD. J. Antibiot. 1989, 42: 1184

<A NAME="RS09206ST-4E">4e</A> Kimura T. Sato Y. Mori M. Tetrahedron 2004, 60: 9649

<A NAME="RS09206ST-4F">4f</A> Donohoe TJ. Sintim HO. Sisangia L. Harling JD. Angew. Chem. Int. Ed. 2004, 43: 2293

<A NAME="RS09206ST-5A">5a</A> Omura S. Matsuzaki K. Fujimoto T. Kosuge K. Furuya T. Fujita S. Nakagawa A. J. Antibiot. 1991, 41: 117

<A NAME="RS09206ST-5B">5b</A> Kainic Acid as a Tool in Neurobiology McGeer EG. Olney JW. McGeer PL. Raven Press; New York: 1978.

<A NAME="RS09206ST-5C">5c</A> Achenbach TV. Slater EP. Brummerhop H. Bach T. Müller R. Antimicrob. Agents Chemother. 2000, 44: 2794

<A NAME="RS09206ST-6A">6a</A> Huck BR. Gellman SH. J. Org. Chem. 2005, 70: 3353

<A NAME="RS09206ST-6B">6b</A> Taylor CM. Hardre R. Edwards PJB. J. Org. Chem. 2005, 70: 1306

<A NAME="RS09206ST-6C">6c</A> Ooi T. Miki T. Marouka K. Org. Lett. 2005, 7: 191

<A NAME="RS09206ST-6D">6d</A> Bisang C. Weber C. Inglis J. Sciffer CA. van Gunsteren WF. Jelesaron I. Bosshard HR. Robinson JA. J. Am. Chem. Soc. 1995, 117: 7904

<A NAME="RS09206ST-7A">7a</A> Hoffmann-Röder A. Krause N. Org. Lett. 2001, 3: 2537

<A NAME="RS09206ST-7B">7b</A> Marshall JA. Wang X.-j. J. Org. Chem. 1991, 56: 4913

<A NAME="RS09206ST-7C">7c</A> Marshall JA. Pinney KG. J. Org. Chem. 1993, 58: 7180

<A NAME="RS09206ST-7D">7d</A> Marshall JA. Bartley GS. J. Org. Chem. 1994, 59: 7169

<A NAME="RS09206ST-8A">8a</A> Prasad JS. Liebeskind LS. Tetrahedron Lett. 1988, 29: 4253

<A NAME="RS09206ST-8B">8b</A> Fox DNA. Gallagher T. Tetrahedron 1990, 46: 4697

<A NAME="RS09206ST-8C">8c</A> Ohno H. Toda A. Miwa Y. Taga T. Osawa E. Yamaoka Y. Fujii N. Ibuka T. J. Org. Chem. 1999, 64: 2992

<A NAME="RS09206ST-9A">9a</A> Dieter RK. Yu H. Org Lett. 2001, 3: 3855

<A NAME="RS09206ST-9B">9b</A> Morita N. Krause N. Org. Lett. 2004, 6: 4121

<A NAME="RS09206ST-10">10</A> Kazmaier U. Görbitz CH. Synthesis 1996, 1489

<A NAME="RS09206ST-11">11</A> Castelhano A. Horne S. Taylor G. Billedeau R. Krantz A. Tetrahedron 1988, 44: 5451

A mixture of 10a and 10b (10a:10b = 2.2:1) was resubmitted to the reaction conditions (11a, AgBF₄ 0.2 equiv, DCE, 0.1 M, 65 °C, 6 h). The ratio of 10a:10b after the reaction was consistent with no detectable isomerization of the oxazines.

<A NAME="RS09206ST-12B">12b</A> For a relevant observation related to the cyclization of α-hydroxy allenes, see: Aurrecoechea JM. Solay M. Tetrahedron 1998, 54: 3851

Isolated yields were ca. 60-70%. The NMR yield was determined by performing the reaction in acetone-d ₆ with mesitylene as an internal standard.

A mechanistic depiction of the chirality transfer in this reaction has been presented in ref. 9b.

The crystallographic data (cif file) were submitted to the Cambridge Crystallographic Data Centre (CCDC 607952).

Sample Procedure for Benzamide Deprotection.
Et₃OBF₄ (Meerwein’s reagent) was prepared as described previously [16b] and stored as a 1.0 M solution in CH₂Cl₂. Benzamide 1a (6.32g, 25.8 mmol) was dissolved in CH₂Cl₂ (250 mL) and Et₃OBF₄ (129 mL, 129.0 mmol of a 1.0 M solution in CH₂Cl₂) was added via cannula under N₂ atmosphere. The reaction mixture was heated to reflux for 2 h when the formation of ethyl imidate was complete. The solvent was then removed under vacuum, and the resulting brown residue was dissolved in THF (100 mL) and H₂O (100 mL) and glacial AcOH (5 mL) was added. The reaction mixture was stirred at r.t. for 12 h. Upon completion of the hydrolysis, HCl (300 mL of a 1.0 M solution) was added and the aqueous layer was extracted with Et₂O (3 × 100 mL) to remove all non-amine organic impurities. The aqueous layer was then carefully basified using NaHCO₃ to prevent foaming and extracted with Et₂O (3 × 150 mL). The organic layer was dried over MgSO₄, and concentrated under vacuum to afford a colorless oil which was purified by column chromatography (gradient elution, 5:1 to 1:1 hexanes-EtOAc, v/v) to afford 12a (2.81 g, 77%).

<A NAME="RS09206ST-16B">16b</A> Org. Synth., Coll. Vol. V Springer; Berlin: 1973. p.1080

Sample Procedure for AgNO ₃ -Catalyzed Cyclization. In a 100-mL round-bottomed flask equipped with a stirring bar, the allenic amine 12d (1.86 mmol, 1 equiv) was added, followed by acetone (36 mL). The flask was then wrapped in aluminum foil to limit exposure to light, sealed with a rubber septum and N₂ was bubbled through the stirred solution for 5 min. Then, AgNO₃ (0.37 mmol, 0.2 equiv) was weighed in the dark and added to the solution and the reaction mixture was stirred for 1 h at r.t. Upon completion, the acetone was removed under vacuum, and the crude residue was redissolved in CH₂Cl₂ (100 mL). The light brown solution was washed with sat. aq NaHCO₃ (2 × 50 mL), then dried over MgSO₄ and concentrated under vacuum to afford the 3-pyrroline 13d in quantitative yield.
Compound 13d: ¹H NMR (300 MHz, CDCl₃): δ = 7.45-7.20 (m, 5 H), 5.92 (dd, J = 5.8, 1.5 Hz, 1 H), 5.86 (dd, J = 5.7, 1.4 Hz, 1 H), 4.08-4.01 (m, 1 H), 3.79 (s, 3 H), 3.35 (d, J = 14.0 Hz, 1 H), 3.09 (d, J = 14.0 Hz, 1 H), 1.11 (d, J = 6.6 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 175.1, 136.7, 136.0, 130.0, 129.8, 127.7, 126.3, 77.0, 60.6, 52.0, 45.4, 22.0. IR (thin film): 3350, 2957, 1734, 1455, 1257 cm^-1. MS: m/z (%) = 232 (25), 172 (80), 141 (75), 108 (57), 51 (100). HRMS (EI): m/z calcd for C₁₂H₁₄N [M - 59⁺]: 172.1126; found: 172.1133.

Sample Procedure for N-Acylation. To a solution of the amine 13d (1.03 mmol, 1 equiv) in CHCl₃ (20 mL) was added Et₃N (3.09 mmol, 3 equiv) and acetyl chloride (2.06 mmol, 2 equiv) at r.t., under N₂ atmosphere. The reaction mixture was stirred for 2 h. The solution was then diluted with CHCl₃ (100 mL), and washed with sat. aq NaHCO₃ (50 mL), sat. aq NH₄Cl (50 mL), dried over MgSO₄ and concentrated under vacuum. Purification by flash chromatography (gradient elution, 4:1 to 1:1 hexane-EtOAc, v/v) afforded the N-acylated 3-pyrroline 14a in 61% yield.
Compound 14a: ¹H NMR (300 MHz, CDCl₃): δ = 7.20-7.15 (m, 3 H), 7.01-6.98 (m, 2 H), 5.59 (0.5 ABq, J = 8.0 Hz, 1 H), 5.56 (0.5 ABq, J = 8.0 Hz, 1 H), 3.95 (d, J = 13.8 Hz, 1 H), 3.89 (q, J = 6.3 Hz, 1 H), 3.74 (s, 3 H), 3.11 (d, J = 13.8 Hz, 1 H), 2.01 (s, 3 H), 1.29 (d, J = 6.2 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.6, 168.8, 136.3, 133.6, 130.5, 127.7, 127.4, 126.2, 77.3, 61.6, 52.5, 37.1, 22.4, 21.0. IR (thin film): 3067, 1732, 1643, 1409 cm^-1. MS: m/z (%) = 273 (8), 214 (10), 172 (29), 140 (100), 91 (70). HRMS (EI): m/z calcd for C₁₄H₁₆NO: [M - 59⁺]: 214.1232; found: 214.1231.

Sample Procedure for Methyl Ester Hydrolysis. To a solution of the methyl ester 14a (0.24 mmol, 1 equiv) in THF (3 mL) was added H₂O (3 mL), followed by LiOH·H₂O (10 equiv) at r.t., and the homogeneous reaction mixture was stirred for 8 h. Upon completion, the reaction mixture was acidified with 1 M HCl and extracted with EtOAc (2 × 50 mL). Upon removal of solvent under vacuum the desired acid was obtained in quantitative yield and sufficient purity to be used in the next step.

Sample Procedure for the Preparation of Amides 15a-f. To a solution of the carboxylic acid (0.077 mmol, 1 equiv) in CH₂Cl₂ (2 mL) at r.t., under N₂ atmosphere, were added the amine (0.16 mmol, 2.1 equiv), 4-(dimethylamino)pyridine (0.084 mmol, 1.1 equiv), 1-hydroxybenzothiazole (0.084 mmol, 1.1 equiv) and 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide HCl (0.16 mmol, 2.1 equiv) in this order. The reaction was stirred at r.t. for 2 h, and then diluted with EtOAc (75 mL). The solution was washed with sat. aq NH₄Cl, 1 M HCl and brine, then dried over MgSO₄ and concentrated under vacuum. Purification by flash chroma-tography (gradient elution, 3:1 to 1:1 hexane-EtOAc, v/v) afforded 15a in 95% yield.
Compound 15a ¹H NMR (300 MHz, CDCl₃): δ = 8.12 (br s, 1 H), 7.27-7.05 (m, 5 H), 5.91 (dd, J = 6.3, 1.8 Hz, 1 H), 5.59 (dd, J = 6.3, 2.0 Hz, 1 H), 4.15 (dd, J = 18.2, 5.9 Hz, 1 H), 4.00 (d, J = 13.8 Hz, 1 H), 4.03-3.98 (m, 1 H), 3.98 (dd, J = 18.2, 4.9 Hz, 1 H), 3.75 (s, 3 H), 3.18 (d, J = 13.8 Hz, 1 H), 2.11 (s, 3 H), 1.30 (d, J = 6.3 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.1, 171.3, 170.3, 135.9, 130.6, 130.3, 130.2, 127.6, 126.5, 79.9, 62.9, 52.2, 41.4, 37.5, 23.2, 22.0. IR (thin film): 3428, 2952, 1752, 1654, 1396 cm^-1. MS: m/z (%) = 330 (25), 299 (15), 214 (91), 172 (75), 91 (100). HRMS (EI): m/z calcd for C₁₈H₂₂N₂O₄ [M⁺]: 330.1580; found: 330.1584.