Synthesis of(+)‐(2S, 6S)‐trans‐α‐Irone and of(‐)‐(2S, 6S)‐trans‐γ‐Irone

Abstract

A 3 :I mixture of (+)-(2S,6S)-trans-a -irone ((+)-1) and (-)-(2S,6S)-rrans-y-irone ((-)-2) has been synthesized with ca. 70% e.e. by the ene reaction of (-)-(S)-3 and but-3-yn-2-one.

Enantioselective Total Synthesis of (+)-(2R,6R)-trans-γ-Irone

“…The high optical purity of (+)-(2 R ,6 R )- 1 was verified by HPLC (column, Chiralcel OD-H, 25 cm × 0.46 cm, i.d. ), and the [α] 25 D +59.4 ( c = 1.2, CH 2 Cl 2 ) is in good agreement with the literature value, which is [α] 25 D −43.3 ( c = 0.8, CH 2 Cl 2 ) for (−)- 1 with a reported 70% ee.…”

“…In 1 H NMR, these rearranged products, which we did not investigate fully, were characterized by a multiplet (bis-allylic hydrogen) at 2.90 ppm.The same isomerization has been reported using ZnCl 2 or ZnBr 2 as Lewis acid and starting from a substituted cyclohexene …”

“…Accordingly, this pair of protons must reside in close proximity; this is uniquely accommodated by A . The preference of molecules related to 6 (or 7 ) to adopt a conformation with a pseudoaxial side chain has been reported in the literature. 2d,, In the same experiment, the NOE effect for vinylic H 7 ‘ and equatorial H 5 ‘ (Chart , B ) established the Z configuration of the double bond in the minor vinylsilane 7 . Further, heating the mixture ( 6 + 7 ) in acetonitrile with a catalytic amount of p -toluenesulfinic acid (TsH), according to the procedure described in the literature for protodesilylation of vinylsilanes, provided (+)- trans -γ-irone ( 1 ) as the only product in 82% yield (Scheme 1, path a).…”

“…The natural occurrence of trans -γ-irone ( 1 ) has recently been demonstrated . Four synthetic routes to the racemate (±)- 1 can be found in the literature, but only one route for (+)-(2 R ,6 R )- 1 and one for (−)-(2 S ,6 S )- 1 have been reported. , These two enantioselective syntheses offer only a moderate enantiomeric excess and lack complete stereo- and/or regioselectivity. In the first synthetic approach, (+)- 1 has to be isolated from its Z -isomer (∼5:1) by chromatography, and, in the second, (−)- 1 is obtained as a 1:3 mixture containing a majority of (+)- trans -α-irone- 2 .…”

“…In a first attempt, based on analogy with the literature, the ZnI 2 -catalyzed H-ene reaction of (+)- 5 with but-3-yn-2-one was investigated. This reaction furnished a mixture of two main products ( 6 + 7 ) and small amounts (9:1) of isomeric derivatives, showing that, prior to the H-ene reaction, a partial isomerization must have taken place .…”