Nezukone

Oxygenated dienes are exceptional substrates for vinylcarbenoids [78]. In order to avoid side-products derived from zwitterionic intermediates, nonpolar solvents are typically employed. A short synthesis of nezukone 57 highhghts the utiHty of the [3-1-4] cycloaddition for the synthesis of tropones (Scheme 14.4). The cycloaddition between the oxygenated butadiene 55 and 52 generates the cycloheptadiene 56 in 67% yield [78]. Treatment of 56 with Meli followed by acid-induced dehydration completes a very short synthesis of nezukone 57. 

The substituted cycloheptane monoterpenes, also called tropones. Eu-carvone 60, nezukone (4-isopropyl-2,4,6-cycloheptatrienone) 61 and y-thujaplicin 62 (Structure 4.14) most probably arise by an unknown ring expansion of the cyclohexane skeleton. 

Secondary halides react with magnesium tributyltin chloride followed by chromium trioxide in pyridine to give good yields of ketones. In one notable example, the carbonyl group of the troponoid, nezukone, was introduced using this methodology (equation 42)361. 

The iron carbonyl-promoted [3 + 4] cycloaddition of bromo-ketones to. 1,3-dienes provides a convenient way, via 2-oxyallyIs, of synthesizing tropones and hence thujaplicins. The synthesis of nezukone (154 X = H)253 has been reported from a,a,a, a -tetrabromoacetone and 3-isopropylfuran. Similarly, from 2-isopropylfuran, /3-thujaplicin (154 X = OH) has been synthesized from the corresponding tropone by known methods, and a-thujaplicin synthesis requires isopropyl substitution in the ketone moiety.254 Karahanaenone (155) is a minor product from pyrolysis of the benzoate (156).149... 

The examples shown in Scheme 2 illustrate (a) a method for RsC— Br -> RzO or R3C—OH and (b) dialkyladve enone transposition as shown in essence in equation (2). The sequence R2CH—Cl R2CH—Sn -> R20 was crucial in a synthesis of the troponoid nezukone (1), as other methods of functionalizing the R2CH—Cl system in this ring failed (equation 3). The dialkylative enone transposition (equation 2) was illustrated by a short synthesis of dihydrojasmone (equation 4). ... 

Oxabicyclo[3.2.1]oct-6-en-3-ones (75) are also readily transformed to tropones (97) or y-tropolones (98) in a few steps. The tricyclic adduct (75 R = (CH2)9) can be readily converted to troponophane (101). Successful use of tetrabromoacetone and tribromo derivatives of methyl alkyl ketones in these reactions opens a new route to various naturally occurring troponoid compounds, viz. nezukone (102), a-thujaplicin (103) and hinokitiol 0-thujaplicin) (104), = respectively (Scheme 24). 

Without the disadvantage of using diazo compounds in the first step, Wenkert s latest monoterpenoid syntheses would be most efficient approaches, and in any case represent novel routes to well-known materials. Nezukone (754) was the result of examining the reaction between butadiene and diazopyruvic ester catalyzed by rhodium tetraacetate. The major product of the addition was the cyclopropane 758 (Scheme 62). It was known that divinylcyclopropanes could be thermolyzed to cycloheptadienes (Vol.4, p.537, Ref.600). The Wittig product from 758 thus gives a cycloheptadiene, and subsequent steps are shown in the scheme. The last step involves Grignard addition to the ester function of the enolate, then loss of water and redistribution of the double bonds.(Further examples of the use of diazo compounds will be found under perillene in the section on furans.)... 

Nezukone, 365 Nickel-aluminum alloy, 289 Nickel boride, 289-290 Nickel carbonyl, 181, 290-293 Nickel catalysts, Raney type, 289,290,293-294, 431... 

Silver fluoroborate, AgBF4 [I, 1007, before Silver iododibenzoate]. Mol. wt. 194.70. Preparation.1 Silver oxide (1.0 g.) is dissolved in 45% fluoroboric acid (7.2 g.). Synthesis of a tropone.1 The natural tropone nezukone (4) has been synthesized by addition of dichlorocarbene (CHClj,-potassium r-butoxide) to l-isopropyl-4-methoxycyclohexadiene-1,4 (2), obtained by Birch reduction of the anisole (1). The resulting adduct (3) was treated with silver fluoroborate to give the tropone (4) in... 

Noyori has transformed 8-oxabicyclooctanones into various naturally-occurring troponoids by acid-induced cleavage of the oxygen bridge, followed by dehydration and oxidation [181]. Equation 122 shows the synthesis of nezukone... 

Use of oxygenated dienes, e.g., 26, leads to the formation of tropone derivatives such as 28. A similar reaction sequence has been applied in the synthesis of nezukone (30)864. 

Cycloheptanes.—N.m.r. spectral data for beryllium bis-(a-iso-propyltropolonate) have been recorded. The full paper on Noyori s syntheses of nezukone, a-thujaplicin, and jS-thujaplicin or hinokitiol (175 R = Pr ) has been published. Compound (175 R = Pr ) has also been synthesized according to Scheme 4, Other syntheses of /3-thujaplicin (175 R = Pr ) have been... 

The reaction of a,a,a, a -tetrabromoacetone, 3-isopropylfurane, and diiron nonacarbonyl was used as the first step in a synthesis of the tropone nezukone... 

This tropone synthesis was used for a short synthesis of nezukone (7) (equation I). 

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