Cyclization of humulene by means of mercury(II) salts. Transannular 1,6-hydride shift in the course of the reaction
✍ Scribed by Shunjiro Misumi; Toshikazu Ohtsuka; Hisanobu Hashimoto; Yasufumi Ohfune; Haruhisa Shirahama; Takeshi Matsumoto
- Publisher
- Elsevier Science
- Year
- 1979
- Tongue
- French
- Weight
- 219 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
In the biosynthesis of illudoids, cyclization of the precursor, humulene (L), is believed to be initiated by attack of proton at the 9,10-double bond of Ltto yield protoilludyl ca;;on(z) [Fig 11. On the other2h;yd, in vitro cyclization reactions of humulene hitherto reported are, except examples by us, ' invariably started by attack of an electrophile at the 6,7-double bond. We described in previous papers humulene cyclization employing mercuric acetate 3, (THF-H20(l/l)/rt, then NaBH4) to 3,6-seco-protoilludane derivatives tand 2. Similarly, treatment with mercuric nitrate (AcOH-H20(2/1)/0+60 "C, then NaBH4) afforded 5-g. 2) Structures of these products suggested that they are formed through the initial attack of Hg++ at the 9,lO bond. 3) The unusual in vitro reaction courses to these compounds have now been shown more complex than appearance. Reduction of the above described intermediary mercurated products from humulene with NaBD4 furnished five deuterated ethers (4,d3, 5,dl, s2, 7d2 and 8dl). Mass spectra indicated the number of incorporated deuterium atoms ( M+=225, 221, 240, 240 and 221 respectively) and location of deuterium atoms was determined on the basis of cmr and pmr spectra as well as some reactions. Comparison of cmr spectra [Table] of deuterated and undeuterated pyranoid 12 4$ R,=H, R2=R3=D g, R,=D 4d3 R,=R2=R3=D !M,R,=D 1) HdN03)2 No. 1 37 oxidation of a-pinene. 5) Absence of deuter double demercuration process i-5 (Fig 3). by the fact that 2 and 5 can be isolated by ium at C-13 of 5, can be explained by assuming a Intervention ofL in the HgN03 reaction is supported quenching the reaction by neutralization (3N NaOH) of the reaction mixture before raising the temperature to 60 'C. A remarkable difference between the pyranoid and furanoid deuterated products is distribution pattern of the deuterium atoms in these compounds, particularly at C-10. While the furanoid group (6d2, 7,d2 and 8d,) carries deuterium at C-10, no deuterium was found at that position in pyranoid products. This can be explained by difference between conformations of the two groups of ethers as follows. In both cases oxymercuration of humulene affords at first ethereal compound L bearing mercury at C-10 as an intermediate. Considering the conformation of 9_ (E_b) obtained by X-ray crystallographic analysis, 3) E_can take a conformation E, in which C-5 and C-10 are close enough to allow the 1,6-hydride shift (Fig 4, course c). Attack of the deuteride at C-5 with concurrent 1,6-hydride shift would give 4,d3, while elimination Of HgX at C-6 accompanied by the 1,6-hydride shift would yield the olefinic ether z, (course d). On the other hand in the corresponding conformer La (or 5) ofI (or g), formed by route a or b (Fig 3), steric situation is different and the 1,6-hydride shift would be difficult. The C-10 deuterated products would thus be formed. The course of the cyclization reactions can thus be summarized as shown in Fig 3. So far as we are aware, 1,6-hydride shift has been only rarely observed. 6) All these cyclization reactions required empirically 3 equivalents of the mercuric salt. This observation coincides with the above proposed reaction paths.
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