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Synlett 2008(15): 2303-2308  
DOI: 10.1055/s-2008-1078169
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Rhodium(I)-Catalyzed Cycloisomerization Reaction of Yne-Allenamides: An Approach to Cyclic Enamides

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

Received 24 February 2008
Publication Date:
28 August 2008 (online)

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Abstract

In this paper, we demonstrate a successful conversion of alkynyl allenamides to triene-containing heterocycles via a rhodium(I)-catalyzed cycloisomerization reaction.

Key words

cycloisomerization - cyclocarbonylation - allenamide - enamide - Diels-Alder

15

General Procedure for the Copper-Catalyzed Coupling Protocol to Prepare an Allenamide - Preparation of 3-(3-Methylbuta-1,2-dienyl)-4-(pent-2-ynyl)oxazolidin-2-one (1b)
A flame-dried 25 mL round-bottom flask was charged with oxazolidinone 8b (0.321 g, 2.10 mmol), copper(I) thiophene-2-carboxylate (CuTC, 0.040 g, 0.21 mmol), BaO (0.643 g, 4.20 mmol), and Cs2CO3 (1.367 g, 4.20 mmol). After flushing with nitrogen, toluene (15 mL) was added, followed by DMEDA (45 µL, 0.42 mmol), then 1-iodo-3-methylbuta-1,2-diene (500 µL, 4.20 mmol). The flask was covered with aluminum foil and heated at 50 ˚C for 20 h. The reaction was then cooled to r.t., filtered through a short pad of Celite, and concentrated in vacuo. The residue was purified by column chromatography [SiO2, eluting with 95% to hexanes-EtOAc (1:1), 5% Et3N] to afford the allenamide 1b (0.363 g, 79%) as a pale yellow oil.
¹H NMR (300 MHz, CDCl3): δ = 6.57 (sept, J = 2.6 Hz, 1 H), 4.43 (app t, J = 8.7 Hz, 1 H), 4.32 (dd, J = 8.8, 4.3 Hz, 1 H), 3.97-3.90 (m, 1 H), 2.54-2.47 (m, 2 H), 2.20-2.11 (m, 2 H), 1.83 (d, J = 2.6 Hz, 3 H), 1.80 (d, J = 2.6 Hz, 3 H), 1.12 (t, J = 7.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 191.5, 155.5, 108.9, 93.0, 85.3, 72.8, 67.1, 53.8, 22.3, 22.0, 21.8, 14.2, 12.5. IR (neat): 1968, 1757 cm-¹. MS: m/z (%) = 220 (10), 219 (50), 204 (31), 190 (68), 152 (88), 108 (87), 81 (100), 67 (92). HRMS (EI): m/z calcd for C13H17NO2 [M+]: 219.1259; found: 219.1259.

16

General Procedure for the Alder-ene Reaction - Preparation of (7 Z )-7-Ethylidene-7,7a-dihydro-6-(prop-1-en-2-yl)pyrrolo[1,2- c ]oxazol-3(1 H )-one (15b)
To a flame-dried test tube equipped with a magnetic stirring bar was added allenamide 14b (0.022 g, 0.12 mmol). The test tube was evacuated and charged with nitrogen (3×). Then, toluene (4.4 mL) was added followed by addition of [Rh(CO)2Cl]2 (0.002 g, 0.01 mmol). The reaction mixture was stirred at r.t. for 3.5 h and upon completion, the light yellow-brown solution was chromatographed [SiO2, hexanes-EtOAc (4:1)] to give the desired cross-conjugated triene 15b (0.016 g, 72% yield). ¹H NMR (300 MHz, CDCl3): δ = 6.67 (s, 1 H), 5.76 (qd, J = 7.2, 3.1 Hz, 1 H), 5.21-5.11 (m, 3 H), 4.84 (app t, J = 8.5 Hz, 1 H), 4.24 (app t, J = 8.7 Hz, 1 H), 1.93 (s, 3 H), 1.68 (dd, J = 7.1, 1.8 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 157.4, 140.1, 135.8, 130.3 130.0, 116.5, 115.0, 70.7, 61.6, 23.3, 16.0. IR (neat): 1772 cm-¹. MS: m/z (%) = 191 (30), 146 (46), 132 (61), 117 (47), 91 (36), 86 (64), 84 (100). HRMS (EI): m/z calcd for C11H13NO2 [M+]: 191.0946; found: 191.0952.

17

( Z )-7,8,9,9a-Tetrahydro-7-methylene-6-vinyl-oxazolo[3,4- a ]azepin-3-(1 H )-one (17a)
Following the general procedure for the Alder-ene reaction, 17a was obtained in 12% yield. ¹H NMR (300 MHz, CDCl3): δ = 6.62 (s, 1 H), 6.32 (dd, J = 17.1, 10.6 Hz, 1 H), 5.33 (dd, J = 17.1, 1.4 Hz, 1 H), 5.24 (br s, 1 H), 5.06 (dd, J = 10.6, 1.4 Hz, 1 H), 5.06 (s, 1 H), 5.05 (s, 1 H), 4.50 (app t, J = 8.4 Hz, 1 H), 4.20-4.10 (m, 1 H), 3.94 (app t, J = 8.4 Hz, 1 H), 2.71-2.65 (m, 1 H), 2.38-2.29 (m, 1 H), 2.16-2.08 (m, 1 H), 1.88-1.77 (m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 156.4, 142.0, 136.5, 126.3, 123.7, 117.9, 114.4, 68.4, 56.9, 35.1, 34.1. IR (neat): 1755, 1640 cm-¹. MS: m/z (%) = 191 (87), 176 (46), 158 (54), 157 (30), 129 (45), 105 (100), 104 (42). HRMS (EI): m/z calcd for C11H13NO2 [M+]: 191.0946; found: 191.0947.

18

General Procedure for the Pauson-Khand Reaction - Preparation of Enone 18a To a flame-dried test tube equipped with a magnetic stirring bar was added allenamide 16d (0.009 g, 0.04 mmol). The test tube was evacuated and charged with carbon monoxide (3×), then toluene (5.2 mL) was added followed by [Rh(CO)2Cl]2 (0.002 g, 0.004 mmol). The reaction mixture was heated at 85 ˚C for 1 h. Upon completion of the reaction (TLC), the mixture was cooled to r.t. and chromatographed [SiO2, hexanes-EtOAc (1:1)] to give 18a as an oil (dr, 3:1, 0.008 g, 75% yield).
Major diastereomer: ¹H NMR (300 MHz, CDCl3): δ = 6.68 (s, 1 H), 4.60 (app t, J = 8.3 Hz, 1 H), 4.19-4.09 (m, 1 H), 3.96 (dd, J = 10.0, 8.5 Hz, 1 H), 3.25 (dt, J = 18.4, 3.2 Hz, 1 H), 2.86-2.76 (m, 2 H), 2.61 (ddd, J = 17.1, 12.8, 3.5 Hz, 1 H), 2.09 (dt, J = 14.1, 4.0 Hz, 1 H), 2.00-1.86 (m, 1 H), 1.24 (d, J = 7.2 Hz, 6 H), 1.20 (d, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 206.6, 159.8, 155.2, 146.5, 123.0, 117.8, 67.6, 58.6, 44.6, 29.2, 28.4, 25.7, 20.3, 20.1, 16.0. IR (neat): 1760, 1682, 1651 cm-¹. MS: m/z (%) = 261 (62), 246 (100), 232 (16), 218 (47), 174 (6). HRMS (EI): m/z calcd for C15H19NO3 [M+]: 261.1365; found: 261.1361.

20

Diels-Alder Reaction - Preparation of Tetracyclic Compound 19 To a solution of triene 2b (0.006 g, 0.03 mmol) in toluene (0.5 mL) was added N-phenylmaleimide (0.005 g, 0.03 mmol). The reaction mixture was heated at 75 ˚C for 5 h then, after cooling to r.t. was chromatographed [SiO2, hexanes-EtOAc, (1:1)] to give the product 19 as a white solid (0.008 g, 75% yield). ¹H NMR (300 MHz, CDCl3): δ = 7.46-7.34 (m, 3 H), 7.11-7.08 (m, 2 H), 5.49 (t, J = 7.5 Hz, 1 H), 4.60 (dd, J = 9.0, 5.8 Hz, 1 H), 4.40 (t, J = 7.4 Hz, 1 H), 4.35-4.34 (m, 1 H), 4.11 (dd, J = 11.5, 7.8 Hz, 1 H), 3.95-3.84 (m, 1 H), 3.27 (ddd, J = 8.9, 7.1, 1.7 Hz, 1 H), 2.77 (dd, J = 14.5, 1.7 Hz, 1 H), 2.69 (dd, J = 12.7, 3.2 Hz, 1 H), 2.40-2.32 (m, 1 H), 2.17-2.07 (m, 2 H), 2.02 (s, 3 H), 1.87 (t, J = 12.3 Hz, 1 H), 1.00 (t, J = 7.5 Hz, 3 H). ¹³C NMR (75 MHz, CD2Cl2): δ = 178.5, 176.7, 157.4, 134.8, 132.5, 130.4, 130.2, 129.3, 128.9, 128.6, 127.1, 69.6, 57.0, 52.8, 40.1, 39.3, 32.3, 28.9, 22.6, 21.7, 14.3. IR (neat): 1746, 1706 cm-¹. MS: m/z (%) = 393 (40), 392 (100), 377 (10), 333 (17), 219 (31), 190 (90), 91 (45). HRMS (EI): m/z calcd for C23H24N2O4 [M+]: 392.1736; found: 392.1719.