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Synlett 2020; 31(06): 627-631
DOI: 10.1055/s-0037-1610746
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© Georg Thieme Verlag Stuttgart · New York

Stereodivergent Metal-Catalyzed Allene Cycloisomerizations

Ryan D. Reeves
a   Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, USA   Email: schomakerj@chem.wisc.edu
,
Caitlin N. Kinkema
b   Blueprint Medicines, 45 Sidney Street, Cambridge, MA 02139, USA
,
Eleanor M. Landwehr
a   Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, USA   Email: schomakerj@chem.wisc.edu
,
Logan E. Vine
a   Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, USA   Email: schomakerj@chem.wisc.edu
,
Jennifer M. Schomaker∗
a   Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, USA   Email: schomakerj@chem.wisc.edu
› Author AffiliationsThis work was funded by the University of Wisconsin and the National Institutes of Health (NIH, Grant No. R01GM111412). The NMR facilities at University of Wisconsin-Madison are funded by the National Science Foundation (NSF, Grant No. CHE-1048642 and CHE-0342998), and the National Institutes of Health (NIH, Grant No. S10 OD012245), as well as a generous gift from Paul J. and Margaret M. Bender. The Thermo Q ExactiveTM Plus Orbi mass spectrometer is supported by the National Institutes of Health (NIH, Grant No. S10 1S10OD020022-1).
Further Information

Publication History

Received: 02 November 2019

Accepted after revision: 20 December 2019

Publication Date:
04 February 2020 (online)

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Published as part of the ISySyCat2019 Special Issue

Abstract

Metal-catalyzed allene cycloisomerizations provide rapid entry into five-membered carbocyclic frameworks, a common motif in natural products and pharmaceuticals. While both Au(I) and Pd(0)-catalyzed allene cycloisomerizations give 5-endo-dig cyclization, Pd prefers the syn diastereomer in contrast to the anti isomer observed with Au. The change in stereoselectivity is proposed to arise from buildup of A1,3 strain during the key carbopalladation step to furnish the cycloisomerized products in moderate to good dr with yields comparable to Au(I) catalysts.

Key words

allene - cycloisomerization - cyclopentene - Conia-ene - carbopalladation - carbocycle

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610746.
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  • 15 Pd(0)-Catalyzed Cycloisomerization of Allenes – General Procedure A flame-dried screw top vial was charged with Pd2dba3 (11.0 mg, 0.012 mmol, 0.05 equiv) and dppm (9.2 mg, 0.024 mmol, 0.10 equiv) in a glove box. The vial was sealed with a septum and removed from the glove box, and anhydrous THF (1.2 mL) was added. The resulting orange solution was stirred at room temperature under an N2 atmosphere for 15 min before a solution of lactone 1h (66.0 mg, 0.24 mmol, 1.00 equiv) in anhydrous THF (1.2 mL) was added, followed by the addition of NaOMe (15.2 mg, 0.28 mmol, 1.20 equiv). The septum was replaced with a screw top, and the resulting suspension was heated to 70 °C and stirred at this temperature for 12 h. After stirring was complete, the solution was cooled to room temperature and quenched by the addition of aqueous NH4Cl (15 mL) and extracted with 3 × 15 mL portions of EtOAc. The combined organics were dried over Na2SO4 and the volatiles removed in vacuo to afford the crude cyclization products. The crude material was purified via flash column chromatography on silica gel using a gradient of 0–20% EtOAc in hexanes to give 33.6 mg (0.12 mmol, 50% isolated yield) of cyclopentene 2h as a pale-yellow oil. 1H NMR (500 MHz, CDCl3): δ (major diastereomer) = 5.61 (dt, J = 3.1, 1.6 Hz, 1 H), 4.24 (d, J = 9.0 Hz, 1 H), 4.05 (d, J = 9.1 Hz, 1 H), 3.76 (s, 3 H), 3.16 (t, J = 6.9 Hz, 1 H), 1.95–1.85 (m, 1 H), 1.69 (t, J = 1.5 Hz, 3 H), 1.49–1.22 (m, overlapping signals, 7 H), 1.28 (s, 3 H), 0.89 (ddd, J = 8.7, 4.4, 2.1 Hz, 3 H); δ (minor diastereomer) = 5.41 (q, J = 1.7 Hz, 1 H), 4.27 (d, J = 9.0 Hz, 1 H), 3.94 (d, J = 9.0 Hz, 1 H), 3.79 (s, 3 H), 3.46 (dddd, J = 9.7, 5.8, 2.8, 1.8 Hz, 1 H), 1.86–1.76 (m, 1 H), 1.66 (dd, J = 2.7, 1.5 Hz, 3 H), 1.50–1.22 (m, overlapping signals, 7 H), 1.07 (s, 3 H), 0.89 (ddd, J = 8.8, 4.4, 2.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 177.0, 173.9, 169.0, 167.2, 140.1, 138.3, 130.3, 129.4, 72.5, 71.7, 65.7, 65.3, 59.7, 57.6, 52.7, 52.3, 50.2, 47.8, 32.4, 31.9, 31.9, 29.1, 28.6, 27.6, 22.6, 22.6, 17.7, 16.4, 14.1, 14.0, 11.9, 11.8. HRMS (ESI): m/z calcd for C16H24O4 [M + H]+: 281.1747; found: 281.1744.