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DOI: 10.1055/s-2007-984880
Steric Promotion of the Intramolecular Pauson-Khand Reaction of Aryl Enynes
Publication History
Publication Date:
12 July 2007 (online)
Abstract
The intramolecular Pauson-Khand reaction of 1,8-enynes derived from salicylaldehyde derivatives has been investigated. Substrates derived from salicylaldehyde itself reacted poorly in this reaction, but related substrates containing ortho-tert-butyl substituents participated quite effectively and in many cases the cyclizations proceeded with high levels of diastereoselectivity.
Key words
organometallic - substituent effects - cyclization - stereoselectivity - cobalt-alkyne complexes
-
1a
Schore NE. Chem. Rev. 1988, 88: 1081 -
1b
Schore NE. Org. React. (N. Y.) 1991, 40: 1 -
1c
Schore NE. In Comprehensive Organometallic Chemistry II, Transition Metal Alkyne Complexes: Pauson-Khand Reaction Vol. 12:Hegedus LS. Pergamon; Oxford: 1995. p.703 -
1d
Geis O.Schmalz H.-G. Angew. Chem. Int. Ed. 1998, 37: 911 -
1e
Ingate ST.Marco-Contelles J. Org. Prep. Proced. Int. 1998, 30: 123 -
1f
Chung YK. Coord. Chem. Rev. 1999, 188: 297 -
1g
Brummond KM.Kent JL. Tetrahedron 2000, 56: 3263 -
1h
Gibson SE.Stevanazzi A. Angew. Chem. Int. Ed. 2003, 42: 1800 -
1i
Blanco-Urgoiti J.Anorbe L.Perez-Serrano L.Dominguez G.Perez-Castells J. Chem. Soc. Rev. 2004, 33: 32 -
1j
Gibson SE.Mainolfi N. Angew. Chem. Int. Ed. 2005, 44: 3022 -
1k
Struebing D.Beller M. Top. Organomet. Chem. 2006, 18: 165 - 2 For an excellent discussion of abnormal cyclization pathways and products, see:
Bonaga LVR.Krafft ME. Tetrahedron 2004, 60: 9795 - For related work with allenynes, see:
-
3a
Ahmar M.Chabanis O.Gauthier J.Cazes B. Tetrahedron Lett. 1997, 38: 5277 -
3b
Mukai C.Nomura I.Yamanishi K.Hanaoka M. Org. Lett. 2002, 4: 1755 -
3c
Brummond KM.Chen HF.Fisher KD.Kerekes AD.Rickards B.Sill PC.Geib SJ. Org. Lett. 2002, 4: 1931 -
3d
Mukai C.Nomura I.Kitagaki S. J. Org. Chem. 2003, 68: 1376 -
3e
Mukai C.Inagaki F.Yoshida T.Yoshitani K.Hara Y.Kitagaki S. J. Org. Chem. 2005, 70: 7159 -
3f
Mukai C.Hirose T.Teramoto S.Kitagaki S. Tetrahedron 2006, 61: 10983 - 4
Krafft ME.Fu Z.Bonaga VR. Tetrahedron Lett. 2001, 42: 1427 -
5a
Blanco-Urgoiti J.Casarrubios L.Pérez-Castells J. Tetrahedron Lett. 1999, 40: 2817 -
5b
Pérez-Serrano L.Blanco-Urgoiti J.Casarrubios L.Domínguez G.Pérez-Castells J. J. Org. Chem. 2000, 65: 3513 -
5c
Perez-Serrano L.Gonzalez-Perez P.Casarrubios L.Dominguez G.Perez-Castells J. Synlett 2000, 1303 -
5d
Blanco-Urgoiti J.Casarrubios L.Dominguez G.Perez-Castells J. Tetrahedron Lett. 2001, 42: 3315 -
5e
Perez-Serrano L.Casarrubios L.Dominguez G.Perez-Castells J. Chem. Commun. 2001, 2602 -
5f
Perez-Serrano L.Dominguez G.Perez-Castells J. J. Org. Chem. 2004, 69: 5413 -
6a
Lovely CJ.Seshadri H. Synth. Commun. 2001, 31: 2479 -
6b
Lovely CJ.Seshadri H.Wayland BR.Cordes AW. Org. Lett. 2001, 3: 2607 -
6c
Madu CE.Seshadri H.Lovely CJ. Tetrahedron 2007, 63: 5019 -
8a For a review of this area, see:
Sammes PG.Weller DJ. Synthesis 1995, 1205 -
8b Also see:
Jung ME.Piizzi G. Chem. Rev. 2005, 105: 1735 - 9 For another example of this abnormal regiochemistry, see:
Comer E.Rohan E.Deng L.Porco JA. Org. Lett. 2007, 9: 2123 -
10a
Shambayati S.Crowe WE.Schreiber SL. Tetrahedron Lett. 1990, 31: 5289 -
10b
Jeong N.Chung YK.Lee BY.Lee SH.Yoo S.-E. Synlett 1991, 204 - 11
Belanger DB.O’Mahony DJR.Livinghouse T. Tetrahedron Lett. 1998, 39: 7637 - 13 For a complementary approach to this type of ring system through the Pauson-Khand reaction, see:
Mohamed AB.Green JR.Masuda J. Synlett 2005, 1543 -
15a
Nicholas KM. Acc. Chem. Res. 1987, 20: 207 -
15b
Green JR. Curr. Org. Chem. 2001, 5: 809 -
15c
Teobald BJ. Tetrahedron 2002, 58: 4133 -
18a Thermodynamic study:
Connor RE.Nicholas KM. J. Organomet. Chem. 1977, 125: C45 -
18b Kinetic study:
Kuhn O.Rau D.Mayr H. J. Am. Chem. Soc. 1998, 120: 900 -
19a
Magnus P.Principe LM. Tetrahedron Lett. 1985, 26: 4851 -
19b
Magnus P.Principe LM.Slater MJ. J. Org. Chem. 1987, 52: 1483
References and Notes
Congested systems arising from the cyclization of internal alkynes and 2,2-disubstituted olefins were generally poor substrates in this reaction. See ref. 6c for further discussion of this issue.
12Our initial explanation of this change was that bulky silyl ether led to an increase in the reactive conformer population, resulting in enhanced cyclization yields. In other words, the silyl ether was serving as a type of steric buttressing element. However, our subsequent experience with related substrates suggests that this may be only one aspect that contributes to the increased yield. We subsequently observed that substrates containing a free propargylic hydroxyl group were prone to several types of side reactions, and its protection may lead to a reduction of these types of reactions.
14Control experiments suggest the diastereomer ratios are kinetically controlled, as the epimeric ketones do not appear to interconvert upon heating in toluene, or on treatment with Et3N, although at this point, we cannot rule out the possibility of a Co-catalyzed epimerization.
16It is also conceivable that the ionization and reduction take place prior to cyclization, and experiments to address this possibility are currently underway.
17It is quite likely that the active complexes (number and type of ligands) are not the same under oxidative and thermal conditions, and thus the differences observed under these two reaction conditions may not only be a result of the temperature differences, but of the precise identity of the active complex.
20The stereochemistry of the major cycloadducts was determined either through NOE experiments, or in the case of 39, by desilylation and comparison to exo-23, to which it was identical.
21Selected experimental procedures and selected characterization data. 4,6-Di-
tert
-butyl-2-(-3-phenyl-2-propynyl)-2-propenyloxybenzene (
19): Triethylsilane (1.24 g, 10.7 mmol) was added at r.t. to a solution of 16 (2.0 g, 5.3 mmol) in CH2Cl2 (10 mL) under a N2 atmosphere. Then trifluoroacetic acid (2.43 g, 21.3 mmol) was added and stirred for 20 min. The reaction mixture was quenched with aq NaHCO3 and extracted with CH2Cl2 (2 × 10 mL) to give a yellow liquid. The crude product was purified by flash chromatography (hexane-EtOAc, 95:5) to give 19 as a light yellow liquid (1.87 g, 98%). 1H NMR (500 MHz, CDCl3): δ = 7.52 (d, J = 2.5 Hz, 1 H), 7.44 (m, 2 H), 7.30 (d, J = 2.5 Hz, 1 H), 7.29 (d, J = 3.0 Hz, 3 H), 6.11 (ddt, J = 4.6, 11.0, 17.0 Hz, 1 H), 5.55 (dq, J = 1.8, 17.4 Hz, 1 H), 5.32 (dq, J = 1.8, 10.5 Hz, 1 H), 4.46 (dt, J = 1.8, 4.6 Hz, 2 H), 3.83 (d, J = 5.0 Hz, 2 H), 1.46 (s, 9 H), 1.38 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 153.6, 146.1, 142.0, 134.0, 131.7, 129.9, 128.3, 127.8, 125.5, 124.0, 123.2, 116.5, 88.7, 82.1, 74.1, 35.5, 34.7, 31.6, 31.3, 20.9. IR (neat): 2959, 2870, 1451, 1225, 991, 755 cm-1. HRMS (ESI): m/z [M + H]+ calcd for C26H33O: 361.2526; found: 361.2538.
General Procedure for the Oxidative PK Reaction (Procedure A): Co2(CO)8 (1.1 equiv) was added to a stirred solution of enyne in CH2Cl2 and under N2 at r.t. The reaction mixture was stirred for 5 h at r.t. The reaction mixture was cooled to 0 °C before NMO (12 equiv) was added in three portions at 30 min intervals and then left to stir for 2 h. The reaction mixture was then filtered through a pad of Celite and SiO2 (ca 1:1) and washed with EtOAc. After rotary evaporation, the crude product was purified by flash chromatography (hexane-EtOAc mixtures).
General Procedure for the Thermal PK Reaction (Procedure B): Co2(CO)8 (1.1 equiv) was added to a stirred solution of enyne in toluene and under N2 and stirred for 5 h at r.t. The reaction mixture was then heated at 70 °C under N2 for overnight. Workup and purification was identical to Procedure A.
6,8-Di-
tert
-butyl-1-phenyl-4,4a-dihydro-3
H
,10
H
-5-oxabenzo[
f
]azulen-2-one (
22): The PK cyclization was carried out according to the general Procedures A and B. The enyne 19 (130 mg, 0.36 mmol) was dissolved in the appropriate solvent (10 mL). Co2(CO)8 (136 mg, 0.40 mmol) and NMO (460 mg, 3.93 mmol) were added according to the general procedure. The crude product was purified by flash chromatography (hexane-EtOAc, 9:1) to afford 22 (60 mg, 43% using Procedure A and 64 mg, 46% using Procedure B) as a yellow solid; mp 160-162 °C. 1H NMR (500 MHz, CDCl3): δ = 7.46 (t, J = 7.8 Hz, 2 H), 7.40 (d, J = 2.8 Hz, 1 H), 7.34 (d, J = 2.8 Hz, 2 H), 7.30 (s, 1 H), 7.14 (s, 1 H), 4.67 (dd, J = 5.5, 11.5 Hz, 1 H), 3.91 (d, J = 12.8 Hz, 1 H), 3.76 (d, J = 12.8 Hz, 1 H), 3.54 (m, 1 H), 3.35 (t, J = 11.5 Hz, 1 H), 2.75 (dd, J = 7.1, 18.9 Hz, 1 H), 2.03 (dd, J = 2.8, 18.8 Hz, 1 H), 1.41 (s, 9 H), 1.35 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 205.5, 172.0, 156.8, 146.7, 141.9, 139.7, 131.3, 129.7, 129.6, 128.3, 128.2, 125.3, 123.0, 76.2, 44.1, 36.9, 36.7, 35.2, 34.7, 31.6, 30.7. IR (neat): 2958, 1705, 1474, 758 cm-1. HRMS (ESI): m/z [M + Na]+ calcd for C27H32O2Na: 411.2295; found: 411.2266.
6,8-Di-
tert
-butyl-10-hydroxy-1-phenyl-4,4a-dihydro-3
H
,10
H
-5-oxabenzo[
f
]azulen-2-one (
25): The PK cyclization of the enyne 16 (250 mg, 0.67 mmol) in the appropriate solvent (10 mL), was carried out following the general Procedures A and B. Co2(CO)8 (250 mg, 0.73 mmol) and NMO (1.22 g, 10.4 mmol) were added according to the general procedures. The crude product was purified by flash chromatography (silica gel, hexane-EtOAc, 90:10) to afford the reduced PK product 22 (142 mg, 55%) and the expected PK product 25 (70 mg, 26%) as a 1:1 mixture of epimers using Procedure A. Procedure B afforded only exo-25 (255 mg, 94%) as a light yellow solid; mp 171-173 °C. 1H NMR (500 MHz, CDCl3): δ = 7.46 (m, 3 H), 7.35 (d, J = 2.8 Hz, 1 H), 7.23 (m, 2 H), 7.14 (d, J = 2.8 Hz, 1 H), 5.49 (d, J = 9.2 Hz, 1 H), 4.61 (dd, J = 5.7, 11.5 Hz, 1 H), 4.09 (m, 1 H), 3.51 (t, J = 11.9 Hz, 1 H), 3.15 (d, J = 8.7 Hz, 1 H), 2.76 (dd, J = 6.9, 19.3 Hz, 1 H), 2.03 (dd, J = 2.8, 18.8 Hz, 1 H), 1.40 (s, 9 H), 1.32 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 205.3, 172.3, 156.3, 147.3, 142.8, 139.6, 133.0, 130.7, 129.6, 128.5, 128.3, 125.1, 125.0, 77.9, 73.7, 38.8, 36.7, 35.3, 34.7, 31.5, 30.7. IR (neat): 3435, 2959, 1702, 1598, 756 cm-1. HRMS (ESI): m/z [M + H]+ calcd for C27H33O3: 405.2424; found: 405.2425.
Some initial experiments with olefins with terminal substitution have been successful, but internal substitution is apparently not tolerated.