Studies towards the Synthesis of Lindenene: Unexpected Stereochemical Outcome of an Intramolecular Cyclopropanation Reaction and Synthesis of (±)-epi-Lindenene and (±)-iso-Lindenene

Abstract

Investigation towards the synthesis of the furanosesqui­terpene Lindenene using an intramolecular cyclopropanation reaction gave unexpected ring-junction isomerisation products. These products were elaborated to (±)-epi-lindenene and (±)-iso-lindenene.

furanosesquiterpene - Hagemann’s ester - cyclopropanation - isomerisation - Julia-Kocienski methylenation

References and Notes

<A NAME="RD25507ST-1">1</A> Takeda K. Ishii H. Tozyo T. J. Chem. Soc. C  1969,  1920 

<A NAME="RD25507ST-2">2</A> Zhang W. Guo Y.-W. Mollo E. Cimino G. Chin. J. Nat. Med.  2003,  1:  13 

<A NAME="RD25507ST-3">3</A> Stellfeld T. Bhatt U. Kalesse M. Org. Lett.  2004,  6:  3889 

<A NAME="RD25507ST-4">4</A> Kametani T. Tsubuki M. Nemoto H. J. Org. Chem.  1980,  45:  4391 

<A NAME="RD25507ST-5">5</A> Friedrich D. Bohlmann F. Tetrahedron  1988,  44:  1369 

<A NAME="RD25507ST-6A">6a</A> Hagiwara H. Uda H. J. Chem. Soc., Perkin Trans. 1  1984,  91 

<A NAME="RD25507ST-6B">6b</A> Honan MC. Tetrahedron Lett.  1985,  26:  6393 

<A NAME="RD25507ST-7A">7a</A> Danheiser RL. Miller RF. Brisbois RG. Park SZ. J. Org. Chem.  1990,  55:  1959 

<A NAME="RD25507ST-7B">7b</A> Danheiser RL. Miller RF. Brisbois RG. Org. Synth., Coll. Vol. IX  1998,  197 

<A NAME="RD25507ST-7C">7c</A> Danheiser RL. Okamoto I. Lawlor MD. Lee TW. Org. Synth.  2003,  80:  160 

<A NAME="RD25507ST-8">8</A> Reissig H.-U. Reichelt I. Kunz T. Org. Synth., Coll. Vol. IX  1998,  573 

<A NAME="RD25507ST-9">9</A> Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis for Diazo Compounds   Wiley; New York: 1998. 

<A NAME="RD25507ST-10A">10a</A> Lightner DA. Gurst JE. Organic Conformational Analysis and Stereochemistry from Circular Dichroism Spectroscopy   Wiley-VCH; New York: 2000.  p.173-230  ; and references therein

<A NAME="RD25507ST-10B">10b</A> Gordon HL. Freeman S. Hudlicky T. Synlett  2005,  2911 

<A NAME="RD25507ST-11">11</A> Matsubara S. Sugihara M. Utimoto K. Synlett  1998,  313 

<A NAME="RD25507ST-12">12</A>

Spectral data for epi-lindenene (12): IR (thin film): 3075, 3005, 2923, 1658, 1451, 1088, 868 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.65-0.71 (1 H, m), 0.89-0.93 (1 H, m), 1.13 (3 H, s, CH₃), 1.47-1.51 (1 H, m), 1.84-1.90 (1 H, m), 1.94 (3 H, s, CH₃), 2.00-2.03 (1 H, m), 2.41-2.43 (1 H, m), 2.44-2.47 (2 H, m), 2.61 (1 H, d, J = 11.5 Hz), 4.48 (1 H, s, R₂C=CH₂), 4.91 (1 H, s, R₂C=CH₂), 7.03 (1 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 8.19, 10.35, 15.93, 21.73, 23.33, 30.67, 34.12, 39.60, 41.09, 101.52, 114.16, 119.47, 136.96, 148.48, 152.56. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₈NaO: 237.1250; found: 237.1250.

<A NAME="RD25507ST-13">13</A>

Spectral data for iso-lindenene (13): ¹H NMR (400 MHz, CDCl₃): δ = 0.64-0.70 (1 H, m), 0.88 (3 H, s, CH₃), 0.89-0.95 (1 H, m), 1.44-1.49 (1 H, m), 1.85-1.89 (1 H, m), 1.93 (3 H, s, CH₃), 1.96-2.00 (2 H, m), 2.47-2.52 (2 H, m), 2.66 (1 H, d, J = 15.5 Hz), 4.66 (1 H, s, R₂C=CH₂), 4.98 (1 H, s), 7.09 (1 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 8.10, 9.92, 17.96, 20.24, 23.10, 28.27, 34.62, 40.74, 42.04, 102.34, 117.37, 119.75, 137.55, 151.34, 152.21. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₈NaO: 237.1250; found: 237.1250.

<A NAME="RD25507ST-14">14</A> Aïssa C. J. Org. Chem.  2006,  71:  360