A-cuparenone

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

Copper-catalyzed ketocarbenoid C/H insertion has been shown to occur with retention of configuration 282 and the same is true for the Rh2(OAc)4-promoted reaction. Advantage has been taken of this fact for a synthesis of (+)-a-cuparenone,... 

The construction of cyclopentanones can take several avenues based upon the concepts evolving from use of small ring conjunctive reagents. A very simple one is a-cuparenone (183) which can be thought to derive by a ring expansion of a cyclobutyl carbinyl system as in 184 (Scheme 8) 110,1U). If X. is an anion stabilizing... 

Like their sulfur counterparts (Section 3.2.4.4.2.), 1 -lithiocyclopropyl selenides 1, as generated by reductive lithiation of bis(selanyl)cyclopropanes 173 with butyllithium in diethyl ether or tetrahydrofuran, react with aldehydes or ketones to give /Lhydroxy selenides 2, which rearrange to cyclobutanones 3 on treatment with p-toluenesulfonic acid in wet benzene.174 175 The method was used in a total synthesis of a-cuparenone.175... 

Chiral 3,3-disubstituted cyclopentanones. Taber et al have extended a synthesis of cyclopentanones by a rhodium catalyzed intramolecular C—H insertion (11,459) to a synthesis of (+ )-a-cuparenone (3), which contains a chiral quaternary center. Thus the chiral a-diazo-p-keto ester 1, prepared by alkylation of a chiral oxazolidone (11, 379-381) on treatment with Rh2(OAc)4 is converted into 2 in 67% yield. This product is converted in several steps into (+ )-3. 

Several applications in total syntheses exemplify the value of this methodology 11-oxoequiienin methyl ether (101 Scheme 38),105 107 (+)-a-cuparenone,109 (-)-podorhizon,112 (-)-methyl jasmonate (102 Scheme 39),114 (+)-estrone methyl ether,116 and the so called (+)-A-factor (103 Scheme 40)117 were all prepared in high enantiomeric purity. Other applications constitute preparations of 2-alkylchro-man-4-ones,118 and of 3-vinylcyclopentanones, highly valuable intermediates for steroid total synthesis.106,107... 

The preparation of 10 represents a formal total synthesis of a-cuparenone. An... 

The utility of the solid-state photodecarbonylation of crystalline ketones was recently demonstrated in the total syntheses of two natural products, where the key step is the solid-state reaction. The first example involves the synthesis of the sesquiterpene ( )-herbertenolide [80] by the solid-state decarbonylation of cyclohexanone 189, followed by cyclization of the photoproduct 190 (Scheme 2.46). With precursor 189 obtained by simple methods and a solid-state reaction carried out to 76% conversion, herbertenolide was obtained in good overall yield in a record number of steps from commercial starting materials. With a similar synthetic strategy, samples of the natural product (i)-a-cuparenone were obtained in about 60% overall yield from 191 by a very succinct procedure that included four simple steps and a solid-state reaction at — 20 °C [81]. 

The enantioselective syntheses of (R)-oc-cuparenone and (S)-a-cuparenone, both of which are natural products from different sources, were also completed using the solid-state photodecarbonylation of diasteromerically pure difluorodioxaborinane ketones 192 and 194 (Scheme 2.47). The latter were prepared in two steps from 191, and irradiated as nanocrystalline suspensions to optimize the chemical yields of the transformation. The photoreaction of the optically pure ketones was 100% stereoselective with an isolated yield of 80%. The two natural products were obtained by simple acid removal of the chiral auxiliary. 

Natarajan, A., Ng, D., Yang, Z., and Garcia-Garibay, M.A. (2007) Parallel syntheses of (+)- and (—)-a-cuparenone by radical combination in crystalline solids. Angewandte Chemie, International Edition, 46, 6485-6487. 

The preparation of 10 represents a formal total synthesis of a-cuparenone. An annulation related to that depicted in eq. 2, which was a key step in an... 

This mechanism implies that, if the C-H bond is at a stereogenic centre, the stereochemistry at that centre will be retained through the reaction, as in Cane s synthesis of pentalenolactone. A nice example of this result is the ingenious synthesis of a-cuparenone using a stereospecific carbene insertion. 

A key feature of intramolecular C-H insertion is the inherent ability to transform an acyclic tertiary stereogenic center into a cyclic quaternary stereogenic center, with retention of absolute configuration [12]. This was first demonstrated by rhodium-mediated cyclization of 29 to 30, leading to (+)-a-cuparenone (31) [13]. 

Another simple synthesis of a-cuparenone (116) based on a [3 + 2] cycloaddition has been published (Scheme 21). ... 

Several natural products, including dihydrojasmone (74), a-cuparenone (75) and cucumin E (76), were synthesized via the ynoiate-initiated tandem process. 

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