Cobalt(I)-Catalysed Neutral Diels-Alder Reactions of Nitrogen-Functionalised Alkynes

Abstract

Imide, sulfimide and amide type protection of nitrogen-functionalised alkynes proofed to be effective protective groups tolerated in cobalt(I)-catalysed Diels-Alder reactions of 1,3-dienes.

alkynes - cobalt - Diels-Alder reaction - 1,3-diene - imides

References

1 Hilt G. Korn TJ. Smolko KI. Synlett  2003,  241 

2

The addition of zinc and zinc iodide leads to an activation of the cobalt pre-catalyst. After a zinc induced reduction step of the Co(II) complex to a Co(I) species and halide abstractions by the mild Lewis acid (ZnI₂) the active catalyst [Co(dppe)]⁺ is formed.

3a Hilt G. Smolko KI. Angew. Chem. Int. Ed.  2003,  42:  2795 ; Angew. Chem. 2003, 115, 2901

3b Hilt G. Lüers S. Synthesis  2003,  1784 

3c Hilt G. Lüers S. Harms K. J. Org. Chem.  2004,  69:  624 

3d Hilt G. Smolko KI. Lotsch BV. Synlett  2002,  1081 

4 A nitro group inhibited the cobalt-catalysed Diels-Alder reaction (see ref. 2c). Nitrogen containing groups also inhibited the cobalt-catalysed hydrovinylation reactions see: Hilt G. Lüers S. Synthesis  2002,  609 ; and unpublished results

For recent applications of propargylic amines in cycloadditions see:

5a Motoda D. Kinoshita H. Shinokubo H. Oshima K. Angew. Chem. Int. Ed.  2004,  43:  1860 ; Angew.Chem. 2004, 116, 1896

5b Fernandez de la Pradilla R. Baile R. Tortosa M. Chem. Commun.  2003,  2476 

5c Varela JA. Castedo L. Saa C. Org. Lett.  2003,  5:  2841 

5d Shibata T. Takasaku K. Takesue Y. Hirata N. Takagi K. Synlett  2002,  1681 

5e Gilbertson SR. DeBoef B. J. Am. Chem. Soc.  2002,  124:  8784 

5f Evans PA. Robinson JE. Baum EW. Fazal AN. J. Am. Chem. Soc.  2002,  124:  8782 

5g Wang B. Cao P. Zhang X. Tetrahedron Lett.  2000,  41:  8041 

5h Rahm A. Rheingold AL. Wulff WD. Tetrahedron  2000,  56:  4951 

5i Paik S.-J. Son SU. Chung YK. Org. Lett.  1999,  1:  2045 

5j Wender PA. Smith TE. J. Org. Chem.  1996,  61:  824 

6 Hilt G. du Mesnil F.-X. Tetrahedron Lett.  2000,  41:  6757 

7

In various reactions involving propargylic ethers, the yields decreased dramatically. On the other hand, using the symmetrical bis-propargylic ether 1,4-dimethoxy-2-butyne the yields were excellent in most cases. See ref. 3.

8

For the Sonogashira reaction the alkyne (1 equiv), iodo benzene (1.2 equiv), Pd(PPh₃)₂Cl₂ (5 mol%), CuI (5 mol%) and Et₃N (5.0 equiv) were stirred in CH₂Cl₂ overnight. The yields of 65-85% were not optimised.

9

Typical Procedure: Synthesis of 2-(4,5-Dimethyl-biphenyl-2-ylmethyl)-isoindole-1,3-dione (Table 2, Entry 1).
To a solution of the protected amine (5, 393 mg, 1.50 mmol) in CH₂Cl₂ (7 mL) were subsequently added Co(dppe)Br₂ (92.6 mg, 0.15 mmol, 10 mol%), Zn (49 mg, 0.75 mmol, 50 mol%), ZnI₂ (239 mg, 0.75 mmol, 50 mol%), and 2,3-dimethyl-1,3-butadiene (0.25 mL, 2.26 mmol, 1.5 equiv). The resulting mixture was stirred overnight at ambient temperature. Then the mixture was filtered (pentane-Et₂O = 1:1) over a short pad of silica gel and concentrated under reduced pressure to give an oily residue that was immediately dissolved in benzene and treated with DDQ (409 mg, 1.80 mmol). An orange precipitate appeared almost immediately. After 2 h the reaction mixture was filtered over a short pad of silica gel (pentane-Et₂O = 1:1), concentrated under reduced pressure and purified by column chromatog-raphy over silica gel (pentane-Et₂O = 2:1) to give the product of type 6 (406 mg, 1.20 mmol, 80%) as a white solid.
¹H NMR (300 MHz, CDCl₃): δ = 7.99 (dd, 2 H, J = 3.1, 5.5 Hz), 7.86 (dd, 2 H, J = 3.1, 5.4 Hz), 7.60 (d, 4 H, J = 3.9 Hz), 7.52 (m, 1 H), 7.20 (d, 2 H, J = 6.6 Hz), 4.90 (s, 2 H), 2.41 (d, 6 H, J = 6.7 Hz). ¹³C NMR (75.5 MHz, CDCl₃): δ = 168.5, 141.2, 139.5, 136.4, 136.0, 134.3, 132.6, 131.9, 131.2, 129.8, 128.7, 128.6, 127.4, 123.6, 39.6, 19.9, 19.7. IR (KBr): 1769, 1708, 1396, 1105, 944, 720, 701 cm^-1. MS (EI): m/z = 341 [M⁺], 281, 253, 194, 165, 105, 77. HRMS (CI): m/z calcd for C₂₃H₁₉NO₂: 341.1416; found: 341.1418.

10 Hilt G. Korn TJ. Tetrahedron Lett.  2001,  42:  2783