Enantioselective One-Pot Rhodium-Catalyzed Cycloisomerization-Wittig Sequence to Chiral Functionalized 4-Alkyl 3-Alkylidene Tetrahydrofuran(on)es

Abstract

Alkyl and (hetero)aryl alkyne allyl alcohols can readily be transformed into chiral 4-alkyl 3-alkylidene tetrahydrofurans and tetrahydrofuranones bearing α,β-unsaturated carbonyl side chains in a one-pot fashion via an enantioselective rhodium-catalyzed ­cycloisomerization-Wittig olefination sequence in good yields (54-86%).

Key words

alkynes - catalysis - cyclization - rhodium - Wittig reactions

References and Notes

• For representative transition-metal-catalyzed cycloisomerization reactions, see the following. Pd:
• 1a Trost BM. Acc. Chem. Res.  1990,  23:  34 
• 1b Trost BM. Janssen Chim. Acta  1991,  9:  3 
• 1c Trost BM. Krische MJ. Synlett  1998,  1 
• Ru:
• 1d Trost BM. Chem. Ber.  1996,  129:  1313 
• 1e Trost BM. Toste FD. Tetrahedron Lett.  1999,  40:  7739 
• Ir:
• 1f Chatani N. Inoue H. Morimoto T. Muto T. Murai S. J. Org. Chem.  2001,  66:  4433 
• 1g Kezuka S. Okado T. Niou E. Takeuchi R. Org. Lett.  2005,  7:  1711 
• Ti:
• 1h Sturla SJ. Kablaoui NM. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  1976 
• Review:
• 1i Aubert C. Buisine O. Malacria M. Chem. Rev.  2002,  102:  813 
• Pd-catalyzed sequences:
• 2a Kressierer CJ. Müller TJJ. Tetrahedron Lett.  2004,  45:  2155 
• 2b Kressierer CJ. Müller TJJ. Synlett  2005,  1721 
• 2c Kressierer CJ. Müller TJJ. Org. Lett.  2005,  7:  2237 
• Ir-catalyzed sequence:
• 2d Kummeter M. Ruff CM. Müller TJJ. Synlett  2007,  717 
• 3 Kressierer CJ. Müller TJJ. Synlett  2004,  655 
• 4 Brummond K. McCabe JM. In Modern Rhodium-Catalyzed Organic Reactions   1st ed.:  Evans PA. Wiley-VCH; Weinheim: 2005.  p.151-171  
• 5a Cao P. Wang B. Zhang X. J. Am. Chem. Soc.  2000,  122:  6490 
• 5b Cao P. Zhang X. Angew. Chem. Int. Ed.  2000,  22:  4104 
• 6a Lei A. He M. Wu S. Zhang X. Angew. Chem. Int. Ed.  2002,  41:  3457 
• 6b Lei A. Waldkirch JP. He M. Zhang X. Angew. Chem. Int. Ed.  2002,  41:  4526 
• 6c Lei A. He M. Zhang X. J. Am. Chem. Soc.  2002,  124:  8198 
• 6d Lei A. He M. Zhang X. Tetrahedron Lett.  2005,  46:  1823 
• 7 Hashmi ASK. Haufe P. Rivas Nass A. Adv. Synth. Catal.  2003,  345:  1237 
• 8a Hashmi ASK. Haufe P. Rivas Nass A. Bats JW. Adv. Synth. Catal.  2004,  346:  421 
• 8b Hashmi ASK. Karch R. Rivas Nass A. Chemistry Today  2006,  24:  16 ; supplement
• 9 Lei A. He M. Zhang X. J. Am. Chem. Soc.  2003,  125:  11472 
• 10 Körber N. Müller TJJ. Chimica Oggi/Chemistry Today  2006,  24:  22 
• 11 Körber N. Rominger F. Müller TJJ. Adv. Synth. Catal.  2009,  351:  2921 

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Typical Procedure (4h, Table 1, Entry 8)
Under argon atmosphere [RhCl(cod)]₂ precursor (12.3 mg, 0.025 mmol) and (R)-BINAP ligand (31.1 mg, 0.05 mmol) were placed in a Schlenk tube. Then dried, degassed DCE
(4 mL) was added, and the solution was stirred for several minutes, until a dark red solution was formed. Then alkyne allyl alcohol 1d (218 mg 1.0 mmol) was added, the solution stirred for another minute, and finally the reaction was started by addition of AgBF₄ solution (1 mL, 0.05 mmol,
c 0.05 M, dissolved in DCE). The reaction was monitored by TLC and full conversion was observed after 5 min at r.t. Then ylide 3b (435 mg, 1.3 equiv, 1.3 mmol) was added. Again the reaction was monitored by TLC and full conver-sion was observed after 30 min at r.t. The mixture was poured into Et₂O (100 mL), filtered, and the solvents were removed in vacuo. The residual crude product was chroma-tographed on silica gel (n-hexane-Et₂O = 1:2; R _f  = 0.51) to give the analytically pure product 4h in form of a yellow solid (193 mg, 0.71 mmol, 71%); mp 57 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 2.34 (s, 3 H), 2.37-2.46 (m, 1 H), 2.52-2.62 (m, 1 H), 2.91-3.01 (m, 1 H), 3.60 (dd, ^² J = 8.7 Hz, ^³ J = 5.3 Hz, 1 H), 3.73 (s, 3 H), 3.95 (dd, ^² J = 8.7 Hz, ^³ J = 6.5 Hz, 1 H), 4.61-4.63 (m, 2 H), 5.90 (dt, ^³ J = 15.6 Hz, ^³ J = 1.5 Hz, 1 H), 6.33 (dd, ^³ J = 4.1 Hz, ^³ J = 2.1 Hz, 1 H), 6.93-7.03 (m, 3 H), 7.15 (d, ^³ J = 8.0 Hz, 2 H). ^¹³C NMR (75.5 MHz, CDCl₃): δ = 21.0 (CH₃), 35.9 (CH₂), 44.2 (CH), 51.4 (CH₃), 70.1 (CH₂), 71.8 (CH₂), 121.3 (CH), 122.7 (CH), 127.8 (CH), 129.2 (CH), 134.1 (C_quat), 136. 5 (C_quat), 142.6 (C_quat), 146.3 (CH), 166.6 (C_quat). IR (KBr pellet): ν = 3430 (br), 2944 (s), 2865 (m), 1718 (s), 1660 (s), 1513 (s), 1431 (m), 1343 (m), 1313 (m), 1296 (m), 1286 (m), 1221 (m), 1203 (m), 1163 (w), 1063 (s), 1041 (m), 979 (m), 935 (m), 880 (w), 810 (m), 521 (s) cm^-¹. UV/Vis (CH₂Cl₂): λ_max (ε) = 262 (20400), 272 nm(14800). MS (EI): m/z (%) = 272 (15) [M]⁺, 174 (14), 173 (100) [C₁₂H₁₃O]⁺, 145 (86) [C₁₀H₉O]⁺, 143 (14), 131 (19), 129 (23) [C₁₀H₉]⁺, 128 (17), 115 (11) [C₈H₈]⁺, 105 (38) [C₈H₉]⁺, 91 (7) [C₇H₇]⁺. HRMS: m/z calcd for C₁₇H₂₀O₃: 272.1412; found: 272.1399. Anal. Calcd (%) for C₁₇H₂₀O₃ (272.14): C, 74.97; H, 7.40. Found: C, 74.94; H, 7.42. (R)-Enantiomer: [α]_D ^²0 +9.3 (c 4.0 mg/mL, CHCl₃). Chiral HPLC: n-hexane-2-PrOH (95:5), 0.8 mL/min, 272 nm, t _R(major) = 17.1 min, t _R(minor) = 18.2 min; ee > 99%.

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CCDC 756431 (4e) and CCDC 756432 (4h) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK; fax:[phone]; or [e-mail]].