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

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

References and Notes

• 1 For a recent review, see: Brummond KM. Loyer-Drew JA. C-C Bond Formation (Part 1) by Addition Reactions: Alder-Ene Reaction, In Comprehensive Organometallic Chemistry III   Vol. 10:  Crabtree RH. Mingos MP. Ojima I. Elsevier; Oxford: 2007.  Chap. 10.12.
• 2a Brummond KM. Chen H. Sill P. You L. J. Am. Chem. Soc.  2002,  124:  15186 
• 2b Brummond KM. Mitasev B. Org. Lett.  2004,  6:  2245 
• 2c Subsequently a similar finding was reported: Shibata T. Takesue Y. Kadowaki S. Takagi K. Synlett  2003,  268 
• For example, see:
• 3a Brummond KM. You L. Tetrahedron  2005,  61:  6180 
• 3b Mitasev B. Yan B. Brummond KM. Heterocycles  2006,  70:  367 ; and references cited therein
• For an enamide cycloisomerization, see:
• 4a Trost BM. Pedregal C. J. Am. Chem. Soc.  1992,  114:  7292 
• 4b Arisawa M. Terada Y. Theeraladanon C. Takahashi K. Nakagawa M. Nishida A. J. Organomet. Chem.  2005,  690:  5398 
• For preparation of cyclic enamides and natural products containing cyclic enamides, see:
• 5a Kinderman SS. Maarseveen JHV. Schoemaker HE. Hiemstra H. Rutjes FPJT. Org. Lett.  2001,  3:  2045 
• 5b Klapars A. Campos KR. Chen C.-Y. Volante RP. Org. Lett.  2005,  7:  1185 
• 5c Zhang X. Zhang Y. Huang J. Hsung RP. Kurtz KCM. Oppenheimer J. Petersen ME. Sagamanova IK. Shen L. Tracey MR. J. Org. Chem.  2006,  71:  4170 
• 5d Toumi M. Couty F. Evano G. Angew. Chem Int. Ed.  2007,  46:  572 
• 5e Yet L. Chem. Rev.  2003,  103:  4283 ; and references cited therein
• 6 For an example, see: Zhang W. Zhang X. Angew. Chem. Int. Ed.  2006,  45:  5515 
• 7 O’Donnell MJ. Plot RL. J. Org. Chem.  1982,  47:  2663 
• 8 Ni Y. Amarasinghe KKD. Ksebati B. Montgomery J. Org. Lett.  2003,  5:  3771 
• 9a Garner P. Park JM. J. Org. Chem.  1987,  52:  2361 
• 9b Koskinen AMP. Otsomaa LA. Tetrahedron  1997,  53:  6473 
• 9c Roush WR. Hunt JA. J. Org. Chem.  1995,  60:  798 
• 10a Seyferth D. Marbor RS. Hilbert P. J. Org. Chem.  1971,  36:  1379 
• 10b Ohira S. Synth. Commun.  1989,  19:  561 
• 11a Crisp GT. Jiang Y.-L. Pullman PJ. Savi CD. Tetrahedron  1997,  53:  17489 
• 11b Meffre P. Gauzy L. Branquet E. Durand P. Goffic FL. Tetrahedron  1996,  52:  11215 
• 11c Meffre P. Gauzy L. Perdigues C. Desanges-Levecque F. Branquet E. Durand P. Goffic FL. Tetrahedron Lett.  1995,  36:  877 
• 12 Trost BM. Stiles DT. Org. Lett.  2005,  7:  2117 
• 13 Shen L. Hsung RP. Zhang Y. Antoline JE. Zhang X. Org. Lett.  2005,  7:  3081 
• 14 For a recent review, see: Wei L.-L. Xiong H. Hsung RP. Acc. Chem. Res.  2003,  36:  773 ; and references cited therein
• 19 Xiong H. Hsung RP. Wei L.-L. Berry CR. Mulder JA. Stockwell B. Org. Lett.  2000,  2:  2869 

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.