Parallel Syntheses of (+)- and (−)-α-Cuparenone by Radical Combination in Crystalline Solids†
Parallel Syntheses of (+)- and (−)-α-Cuparenone by Radical Combination in Crystalline Solids†
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DOI：
10.1002/anie.200700679
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发表时间：
2007-08
影响因子：
--
通讯作者：
Arunkumar Natarajan;D. Ng;Z. Yang;M. Garcia‐Garibay
中科院分区：
文献类型：
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作者：
Arunkumar Natarajan;D. Ng;Z. Yang;M. Garcia‐Garibay
Among the forces shaping the future of organic synthesis is the drive for environmentally friendly processes in keeping with the principles of green chemistry.[1] Strategies under development include the engineering of microorganisms and enzymes,[2] the application of efficient catalysts [1, 3] and environmentally friendly solvents,[4] and whenever possible, the use of chemical processes without solvents.[5, 6a] It is also expected that photochemical reactions will play an important role in the synthesis of natural products and specialty chemicals.[6, 7] A promising reaction in this context is the solvent-free photodecarbonylation of crystalline ketones (Scheme 1).[6a, 8] While the reaction is ideal for the synthesis of molecules with adjacent quaternary stereogenic centers,[9] its application for the synthesis of enantiomerically pure natural products has not been demonstrated.[10, 11] With that in mind, we report here a very efficient synthesis of the natural product (α)-cuparenone (1), in which the two quaternary centers are formed in the crystalline state with complete stereocontrol (Scheme 2).(α)-Cuparenone (1) is a crystalline compound and a suitable candidate for a solid-to-solid photochemical reaction.(S)-(+)-(α)-Cuparenone was first isolated from the wood of the Mayur Pankhi in 1964 [12] and (R)-(À)-(α)-cuparenone from the liverwort Mannia fragrans in 1976.[13] With two adjacent quaternary centers, one of which is stereogenic,(α)-cuparenone has been one of the most sought-after targets to test novel methodologies, thus providing a good standard for comparison.[14] As a starting point, we prepared racemic cyclohexanedione (Æ)-2 in four simple steps in 59.7% overall yield from methyl 2-tolyl-acetate (3)(Scheme3). Clear prisms of (Æ)-2 (mp 63.0–65.58 C) obtained from hexane were suitable for photochemical studies.Irradiation of (Æ)-2 in degassed 0.1 m benzene solutions with a medium-pressure Hg Hanovia lamp using a Pyrex filter (λ> 290 nm) gave (Æ)-(α)-cuparenone in 34% yield along with several other products after 100% percent conversion.[15] In contrast, irradiation of (Æ)-2 in powder form (20 mg) at À208C yielded (Æ)-(α)-cuparenone as the only product at 70% conversion. Larger samples (0.1 g) conveniently irradiated at ambient temperature as nanocrystalline suspensions [16–18] provided (Æ)-α-cuparenone in 85% yield. To prepare the enantiomerically pure natural products we carried out a classical resolution of (Æ)-2 via the diastereo-
