Intramolecular Cyclocarbonylation of Cyclopropylidenyl Aldehydes Mediated by Molybdenum Carbonyl Complex

Abstract

A novel procedure for the synthesis of cis-bicyclic spirocyclopropanelactones from cyclopropylidenyl aldehydes via the molybdenum-mediated cyclocarbonylation is described. The use of (C₇H₈)Mo(CO)₃ with DMSO to promote the reaction results in an efficient and convenient protocol for the three-component assembly in high yields.

aldehydes - carbonyl complexes - cyclizations - cyclopropane - molybdenum

References

For excellent discussions, see:

1a Ojima I. Tzamarioudaki M. Li Z. Donovan R. Chem Rev.  1996,  96:  635 

1b Lautens M. Klute W. Tam W. Chem. Rev.  1996,  96:  49 

1c Trost BM. Toste FD. Pinkerton AB. Chem. Rev.  2001,  101:  2067 

1d Aubert C. Buisine O. Malacria M. Chem. Rev.  2002,  102:  813 

For general discussions, see:

2a Transition Metals for Organic Synthesis   Vol I:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998. 

2b Transition Metals for Organic Synthesis   Vol II:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998. 

3a Kablaoui NM. Buchwald SL. J. Am. Chem. Soc.  1995,  117:  6785 

3b Kablaoui NM. Buchwald SL. J. Am. Chem. Soc.  1996,  118:  3182 

3c Kablaoui NM. Hick FA. Buchwald SL. J. Am. Chem. Soc.  1996,  118:  5818 

3d Kablaoui NM. Hick FA. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  4424 

4a Crowe WE. Vu AT. J. Am. Chem. Soc.  1996,  118:  1557 

4b Mandal SM. Amin SR. Crowe WE. J. Am. Chem. Soc.  2001,  123:  6457 

5 Trost BM. Acc. Chem. Res.  2002,  35:  695 

6 Chatani N. Morimoto T. Fukumoto Y. Murai S. J. Am. Chem. Soc.  1998,  120:  5335 

7a Yu C.-M. Yoon S.-K. Baek K. Lee J.-Y. Angew. Chem. Int. Ed.  1998,  37:  2392 

7b Yu C.-M. Kim Y.-M. Kim J.-M. Synlett  2003,  1518 

8a Kang S.-K. Hong Y.-T. Lee J.-H. Kim W.-Y. Lee I. Yu C.-M. Org. Lett.  2003,  5:  2813 

8b Kang S.-K. Kim K.-J. Hong Y.-T. Angew. Chem. Int. Ed.  2002,  41:  1584 

8c Kang S.-K. Kim K.-J. Yu C.-M. Hwang J.-W. Do Y.-K. Org. Lett.  2001,  3:  2851 

9 For a review see: Goti A. Cordero FM. Brandi A. In Small Ring Compounds in Organic Synthesis V   de Meijere A. Springer; Berlin: 1996.  p.1-98  

10a Stolle A. Becker H. Salauen J. de Meijere A. Tetrahedron Lett.  1994,  35:  3521 

10b Takano S. Inomata K. Ogasawara K. J. Chem. Soc., Chem. Commun.  1992,  169 

11 Ang KH. Braese S. Steinig AG. Meyer FE. Liebaria A. Voigt K. de Meijere A. Tetrahedron  1996,  52:  11503 

12a Estieu K. Paugam R. Ollivier J. Salauen L. J. Org. Chem.  1997,  62:  8276 

12b Ferrara M. Cordero FM. Goti A. Brandi A. Estieu K. Paugam R. Ollivier J. Salaun J. Eur. J. Org. Chem.  1999,  2725 

12c Pisaneschi F. Cordero FM. Goti A. Paugam R. Ollivier J. Brandi A. Salaun J. Tetrahedron: Asymmetry  2000,  11:  897 

13 For a review see: Gibson SE. Stevenazzi A. Angew. Chem. Int. Ed.  2003,  42:  1800 ; and references cited therein

14a Jeong N. Lee SJ. Tetrahedron Lett.  1993,  34:  4027 

14b Brummond KM. Kerekes AD. Wan H. J. Org. Chem.  2002,  67:  5156 

15

General Procedure: A flame-dried sealed tube containing C₇H₈Mo(CO)₃ (152.0 mg, 0.56 mmol) was evacuated and carefully purged with argon three times and then charged with 3a (103.0 mg, 0.37 mmol) in dry toluene (3 mL). Freshly distilled DMSO (0.27 mL, 289 mg, 3.80 mmol) was then added at 20 °C. After stirring at 20 °C for 1 h, the reaction mixture was heated and allowed to proceed at 90 °C for 5 h. The resulting mixture was treated with EtOAc. The combined organics were washed with H₂O (3 ×) and brine (1 ×). The organic layer was dried over anhyd MgSO₄, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (EtOAc-hexane, 1:1) to give 4a (83.0 mg, 0.27 mmol, 73%) as a colorless oil: R_f = 0.37 (EtOAc-hexane, 1:1).

16

¹H NMR and ¹³C NMR data: Compound 4a: ¹H NMR (500 MHz, CDCl₃): δ = 1.03 (dt, 2 H, J = 3.1, 5.6 Hz), 1.31 (dt, 2 H, J = 3.1, 8.2 Hz), 2.45 (s, 3 H), 2.82 (ddd, 1 H, J = 3.9, 8.2, 7.6 Hz), 3.06 (dd, 1 H, J = 7.6, 10.4 Hz), 3.19 (dd, 1 H, J = 3.9, 10.4 Hz), 3.22 (dd, 1 H, J = 5.3, 11.5 Hz), 3.61 (d, 1 H, J = 11.5 Hz), 5.06 (ddd, 1 H, J = 0.6, 5.3, 8.2 Hz), 7.35 (d, 2 H, J = 8.2 Hz), 7.69 (d, 2 H, J = 8.2 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 178.6, 144.6, 132.1, 130.1, 128.2, 79.7, 54.6, 52.3, 44.1, 24.8, 21.8, 18.4, 13.0. Compound 4b: ¹H NMR (500 MHz, CDCl₃): δ = 1.29 (d, 3 H, J = 6.7 Hz), 2.42 (s, 3 H), 2.42 (dd, 1 H, J = 3.7, 6.8 Hz), 3.73 (dq, 1 H, J = 3.7, 6.7 Hz), 3.74 (dd, 1 H, J = 4.5, 13.2 Hz), 3.86 (dd, 1 H, J = 0.8, 13.2 Hz), 5.01 (ddd, 1 H, J = 0.8, 4.5, 6.8 Hz), 7.30 (d, 2 H, J = 8.2 Hz), 7.70 (d, 2 H, J = 8.2 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 177.8, 144.3, 135.6, 130.1, 127.4, 80.3, 61.2, 53.3, 53.1, 25.4, 22.0, 21.8, 18.6, 12.2. Compound 4c: ¹H NMR (500 MHz, CDCl₃): δ = 0.83 (ddd, 1 H, J = 4.5, 7.3, 9.6 Hz), 1.03 (s, 3 H), 1.06 (ddd, 1 H, J = 4.5, 7.3, 10.1 Hz), 1.11 (ddd, 1 H, J = 4.5, 7.3, 9.6 Hz), 1.31 (ddd, 1 H, J = 4.5, 7.3, 10.1 Hz), 2.45 (s, 3 H), 2.97 (d, 1 H, J = 10.1 Hz), 3.09 (d, 1 H, J = 10.1 Hz), 3.45 (dd, 1 H, J = 1.7, 11.9 Hz), 3.58 (dd, 1 H, J = 5.3, 11.9 Hz), 4.56 (dd, 1 H, J = 1.7, 5.3 Hz), 7.35 (d, 2 H, J = 8.2 Hz), 7.68 (d, 2 H, J = 8.2 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 178.4, 144.5, 132.6, 130.1, 128.0, 86.2, 58.4, 53.7, 47.4, 28.9, 21.8, 20.6, 14.0, 12.3. Compound 4d: (major) ¹H NMR (500 MHz, CDCl₃): δ = 0.99 (m, 1 H), 1.05 (m, 2 H), 1.33 (m, 1 H), 1.45 (d, 3 H, J = 6.8 Hz), 2.44 (s, 3 H), 2.84 (ddd, 1 H, J = 5.6, 6.2, 7.9 Hz), 3.37 (dd, 1 H, J = 4.5, 7.9 Hz), 3.40 (dd, 1 H, J = 4.5, 6.2 Hz), 4.13 (dq, 1 H, J = 6.2, 7.3 Hz), 4.87 (dd, 1 H, J = 5.6, 7.3 Hz), 7.34 (d, 2 H, J = 8.2 Hz), 7.71 (d, 2 H, J = 8.2 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 178.7, 144.4, 133.7, 130.1, 127.5, 86.5, 62.1, 51.6, 43.6, 25.6, 21.8, 18.7, 17.9, 12.1. Compound 4d (minor) ¹H NMR (500 MHz, CDCl₃): δ = 0.88 (m, 1 H), 1.05 (m, 2 H), 1.18 (m, 1 H), 1.37 (d, 3 H, J = 6.7 Hz), 2.42 (s, 3 H), 2.63 (ddd, 1 H, J = 5.1, 6.5, 7.9 Hz), 3.19 (dd, 1 H, J = 7.9, 11.0 Hz), 3.20 (dd, 1 H, J = 5.1, 11.0 Hz), 3.68 (dq, 1 H, J = 6.7, 11.0 Hz), 4.66 (dd, 1 H, J = 6.5, 11.0 Hz), 7.31 (d, 2 H, J = 8.2 Hz), 7.69 (d, 2 H, J = 8.2 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 177.7, 144.3, 135.1, 130.1, 128.0, 82.8, 60.2, 52.6, 42.0, 24.9, 21.8, 18.2, 15.2, 12.8. Compound 4e: ¹H NMR (500 MHz, CDCl₃): δ = 1.05 (m, 2 H), 1.25 (t, 3 H, J = 7.0 Hz), 1.26 (t, 3 H, J = 7.0 Hz), 1.27 (m, 1 H), 1.35 (m, 1 H), 2.24 (dd, 1 H, J = 9.3, 13.8 Hz), 2.43 (dd, 1 H, J = 6.2, 13.8 Hz), 2.66 (dd, 1 H, J = 2.5, 14.9 Hz), 2.72 (dd, 1 H, J = 5.9, 14.9 Hz), 2.76 (ddd, 1 H, J = 6.2, 7.0, 9.3 Hz), 5.11 (ddd, 1 H, J = 2.5, 5.9, 7.0 Hz), 4.18 (q, 2 H, J = 7.0 Hz), 4.20 (q, 2 H, J = 7.0 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 179.5, 171.4, 170.7, 82.4, 62.2, 60.6, 44.8, 41.3, 38.7, 26.5, 18.9, 14.2, 12.7.