Protecting Group Effects on the Efficiency of the Ruthenium-Catalyzed Alder-Ene Reaction

Abstract

The efficiency of the ruthenium-catalyzed Alder-ene reaction of hydroxy alkenes depends heavily on the nature of the O-protecting groups employed, as well as the length of the carbon spacer between the hydroxy and alkene group.

Key words

Alder-ene reaction - ruthenium catalysis - O-protecting groups

References

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• For examples of internal coordination directing β-hydrogen elimination in Alder-ene reactions:
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• 8a

  For CpRu(η⁶-anisole)BF₄: ¹H NMR (d ₆-acetone): δ = 5.51 (s, 5 H, CpH), 6.13-6.53 (m, 5 H, ArH).

• 8b Volkenau NA. Bolesova IN. Shulpina LS. Kitaigorodskii AN. Kravtsov DM. J. Organomet. Chem.  1985,  288:  341 

2

(1 Z ,4 E )-( R )-1-Trimethylsilyl-2-(2′-methyl-3′- tert -butyldiphenylsilyloxy)-6-acetoxy-1,4-hexadiene. CpRu(MeCN)₃PF₆ (39 mg, 0.090 mmol) under Ar was treated with an acetone solution (2 mL) of 1-acetoxy-3-butene (170 mg, 1.5 mmol) and (R)-1-(trimethylsilyl)-4-methyl-5-(tert-butyldiphenylsilyloxy)-1-pentyne (123 mg, 0.300 mmol). The yellow solution was stirred at r.t. for 20 h. The reaction mixture was passed through a short plug of silica and concentrated in vaccuo. The residue was purified by column chromatography (increasing polarity from 1% to 10% EtOAc in petroleum spirit), which gave the title compound (134 mg, 0.256 mmol, 85% yield) as a colorless oil. R_f (11% EtOAc in petroleum spirit): 0.67. [α]_D ²⁵ +1.1 (c 6.7, CH₂Cl₂). MS (ES+): m/z (%) = 463.28 (100) [M - OAc], 540.32 (23) [M + NH₄ ⁺], 545.29 (33) [M + Na⁺], 561.26 (12) [M + K⁺], 655.20 (33) [M + Cs⁺]. HRMS (ES+): m/z [M + Na⁺] calcd for C₃₁H₄₆O₃NaSi₂: 545.2883; found: 545.2904. ¹H NMR (300 MHz, CDCl₃): δ = 0.06 [9 H, s, (CH₃)₃Si], 0.86 (3 H, d, J = 6.0 Hz, CH₃CH), 1.06 [9 H, s, (CH₃)₃CSi], 1.82-2.02 (2 H, m, CH₃CH and CHCH₂C=), 2.05 [3 H, s, CH₃C(O)O], 2.27 (1 H, dd, J = 12.9, 4.8 Hz, CH₃CH), 2.74 (2 H, d, J = 6.6 Hz, =CHCH₂CH=), 3.47 (2 H, d, J = 6.0 Hz, CH₂OSi), 4.52 (2 H, d, J = 6.3 Hz, CH₂OAc), 5.23 (1 H, s, TMSCH), 5.54 (1 H, dt, J = 15.3, 6.3 Hz, AcOCH₂CH=CH), 5.73 (1 H, dt, J = 15.6, 6.9 Hz, AcOCH₂CH=CH), 7.36-7.44 (6 H, m, SiPh), 7.62-7.68 (4 H, m, SiPh). ¹³C NMR (75 MHz, CDCl₃): δ = 0.8 (CH₃), 16.4 (CH₃), 19.5 (C), 21.2 (CH), 27.2 (CH₃), 34.2 (CH₃), 39.6 (CH₂), 41.8 (CH₂), 65.3 (CH₂), 69.5 (CH₂), 125.8 (CH), 126.8 (CH), 127.8 (CH), 129.8 (CH), 134.1 (C), 134.3 (CH), 135.9 (CH), 155.3 (C), 171.0 (C=O).

4

Whilst there are examples of other processes occurring when β-hydrogen elimination is inhibited,⁵ under the mild conditions employed only starting materials are recovered.