Diene RCM in the Presence of a Protected Alkyne

Abstract

Diene RCM reactions with Grubbs catalyst proceed in the presence of a terminal alkyne protected by TMS or dicobalt hexacarbonyl complex, and this reaction was used to synthesize a key intermediate for nakadomarin A (2).

Key words

nakadomarin A - ring-crosing olefin metathesis (RCM) - enyne metathesis - Grubbs catalyst - dicobalt hexacarbonyl complex

References

• For recent reviews on metathesis, see:
• 1a Armstrong SK. J. Chem. Soc., Perkin Trans. 1  1998,  371 
• 1b Fürstner A. Angew. Chem. Int. Ed.  2000,  39:  3013 
• 1c Trnka TM. Grubbs RH. Acc. Chem. Res.  2001,  34:  18 
• For recent reviews on enyne metathesis with ruthenium carbene complexes, see:
• 2a Poulsen CS. Madsen R. Synthesis  2003,  1:  1 
• 2b For examples with other transition metals, see: Katz TJ. Sivavec TM. J. Am. Chem. Soc.  1985,  107:  737 
• 2c Trost BM. Tanoury GJ. J. Am. Chem. Soc.  1988,  110:  1636 
• 2d Barrett AGM. Baugh SPD. Braddock DC. Flack K. Gibson VC. Giles MR. Marshall EL. Procopiou PA. White AJP. Williams DJ. J. Org. Chem.  1998,  63:  7893 
• 2e See also: Trost BM. Doherty GA. J. Am. Chem. Soc.  2000,  122:  3801 
• 2f Fürstner A. Szillat H. Stelzer F. J. Am. Chem. Soc.  2000,  122:  6785 
• 2g See also: Fürstner A. Stelzer F. Szillat H. J. Am. Chem. Soc.  2001,  123:  11863 
• 2h Chatani N. Inoue H. Morimoto T. Muto T. Murai S. J. Org. Chem.  2001,  66:  4433 
• 3a Kitamura T. Sato Y. Mori M. Adv. Synth. Catal.  2002,  344:  678 
• 3b Kinoshita A. Sakakibara N. Mori M. Tetrahedron  1999,  55:  8155 
• 4a For an example of diene ring-closing metathesis with a tungsten catalyst in the presence of an alkyne, see: Kim S.-H. Zuercher WJ. Bowden NB. Grubbs RH. J. Org. Chem.  1996,  61:  1073 
• 4b For an example of olefin cross metathesis with Grubbs catalyst in the presence of an alkyne, see: Ratnayake AS. Hemscheidt T. Org. Lett.  2002,  4:  4667 
• 5 Synthesis of medium-rings by diene metathesis using substrates having an inner dicobalt hexacarbonyl complex using Grubbs first generation catalyst or molybdenum carbene catalyst has been reported very recently: Young DGJ. Burlison JA. Peters U. J. Org. Chem.  2003,  68:  3494 
• 6 Kobayashi J. Watanabe D. Kawasaki N. Tsuda M. J. Org. Chem.  1997,  62:  9236 
• 8 Scholl M. Ding S. Lee CW. Grubbs RH. Org. Lett.  1999,  1:  953 
• 9 Under the forced conditions using 15 mol% of the catalyst, 3e gave 4e in 64% yield, and isomerization of vinylsilane to Z:E = 3:2 was observed. For an example of isomerization of olefin with second-generation Grubbs catalyst B, see: Lee CW. Grubbs RH. Org. Lett.  2000,  2:  2145 
• 10a For a recent example of decomplexation into an alkyne, see: Jones GB. Wright JM. Rush TM. Plourde GWII. Kelton TF. Mathews JE. Huber RS. Davidson JP. J. Org. Chem.  1997,  62:  9379 
• 10b For an example of reductive decomplexation into an alkene, see: Takai S. Ploypradith P. Hamajima A. Kira K. Isobe M. Synlett  2002,  588 

7

Nagata, T.; Nakagawa, M.; Nishida, A. J. Am. Chem. Soc. 2003, 125, in press.

11

A Typical Experimental Procedure for the Metathesis Reaction of 3c: Grubbs catalyst B (1.2 mg, 5 mol%) was added to a solution of 3c (20.4 mg, 28.7 mmol, Table [1] , entry 5) in CH₂Cl₂ 29 mL (1 mmol) which was not degassed under a dry argon atmosphere. The resulting solution was placed in a 50 °C oil bath. After 1.5 h, the starting material 3c was completely converted to the cyclized product 4c on TLC. The solution was concentrated under reduced pressure and purified by flash chromatography on silica gel to give 4c (18.8 mg, 98%) as a red oil.

12

Spectral data for 4c and 7b. 2-(1-Phenylsulfonylamino-5-hexynyl)-5,10-dioxa-5,6,9,10-tetrahydrobenzocyclooctene-dicobalt hexacarbonyl complex (4c): IR (KBr): n = 3067, 2929, 2521, 2090, 2048, 2021, 1577, 1497, 1446, 1350, 1300, 1267, 1168, 1116, 1020, 999, 838, 739, 723 cm^-1.
¹H NMR (400 MHz, CDCl₃): d = 1.55-1.68 (m, 4 H), 2.82 (t, J = 7.2 Hz, 2 H), 3.50 (t, J = 6.7 Hz, 2 H), 4.81 (d, J = 4.9 Hz, 2 H), 4.92 (d, J = 4.4 Hz, 2 H), 5.88 (dt, J = 11.0, 4.4 Hz, 1 H), 5.91 (dt, J = 11.0, 4.9 Hz, 1 H), 5.95 (s, 1 H), 6.59 (d, J = 2.7 Hz, 1 H), 6.68 (dd, J = 2.7, 8.5 Hz, 1 H), 6.87 (d, J = 8.5 Hz, 1 H), 7.46 (dd, J = 7.8, 7.8 Hz, 2 H), 7.57 (t, J = 7.8 Hz, 1 H), 7.60 (d, J = 7.8 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): d = 27.9, 28.4, 33.6, 50.3, 69.7, 70.7, 73.1, 96.6, 122.5, 122.9, 124.5, 127.7 (2 C), 128.7 (2 C), 128.9, 129.7, 132.6, 133.9, 138.1, 147.9, 148.0, 199.9 (6 C). LRMS (FAB): m/z = 684 [M + H]⁺. HRMS (FAB): Calcd for C₂₈H₂₄Co₂NO₁₀S [M + H]⁺ 683.9785. Found: 683.9781. (6aS,7aS,11aS,14bS)-13-(3-Butynyl)-9-(phenylsulfonyl)-3,4,6a,7,8,9,10,11,11a,14b-decahydrofuro[2¢¢3 ¢¢:3¢,4¢]pyri-do[3¢¢,4¢¢:1¢,5¢]cyclopenta[1¢,2¢:4,5]pyrrolo[1,2-a]azocin-1(2H)-one-dicobalt hexacarbonyl complex (7b): [a]²³ _D -38.8 (c 0.10, CHCl₃). IR (neat): n = 3063, 2927, 2856, 2091, 2049, 2015, 1651, 1462, 1409, 1543, 1268, 1199, 1161, 1092, 981, 740, 691 cm^{-1 1}H NMR (600 MHz, CDCl₃): d = 1.43-1.52 (m, 1 H), 1.69-1.77 (m, 1 H), 1.99-2.09 (m, 4 H), 2.22-2.30 (m, 1 H), 2.33-2.37 (m, 2 H), 2.58-2.65 (m, 2 H), 2.92 (t, J = 7.4 Hz, 2 H), 2.98-3.01 (m, 1 H), 3.01 (d, J = 12.7 Hz, 1 H), 3.15-3.26 (m, 2 H), 3.29-3.33 (m, 1 H), 3.51 (d, J = 12.7 Hz, 1 H), 4.55-4.58 (m, 1 H), 5.09 (s, 1 H), 5.46 (d, J = 12.1 Hz, 1 H), 5.73-5.79 (m, 1 H), 5.90 (s, 1 H), 5.97 (s, 1 H), 7.52 (dd, J = 7.7, 8.1 Hz, 2 H), 7.60 (t, J = 7.7 Hz, 1 H), 7.75 (d, J = 8.1 Hz, 2 H). ¹³C NMR (150 MHz, CDCl₃): d = 29.1, 30.9, 32.50, 32.55, 39.0, 43.08, 43.13, 49.7, 56.8, 59.7, 63.0, 73.4, 95.5, 103.4 (2 C), 127.4, 129.1 (2 C), 129.3 (2 C), 132.7, 133.8, 137.4, 155.5, 159.8, 173.3, 199.7 (6 C). LRMS (FAB): m/z = 777 [M + H]⁺. HRMS (FAB): Calcd for C₃₄H₃₁Co₂N₂O₁₀S [M + H]⁺ 777.0339. Found: 777.0363.