7?-Mintlactone, synthesis

In a similar approach, Shishido et al. (241) used oxime 215 [derived from the monoterpene (+)-citronellal (214)] for the synthesis of (—)-mintlactone (218) and (+)-isomintlactone (219), sweet compounds isolated from some Mentha species (Scheme 6.89). Bicyclic isoxazoline 216 was obtained in good yield from the cycloaddition. As expected, the product possessing tra i-l,4-substimtion prevailed. Reductive hydrolysis of the major isomer of 216 using hydrogen-Raney Ni-trimethyl borate provided p-hydroxyketone 217. This compound was dehydrated to give an enone and this was followed by carbonyl reduction-lactonization to complete the synthesis of both lactones 218 and 219 (241). 

Synthesis of mintlactone and isomintlactone, terpene lactones from mint oil 02S2155. 

Axial hydride delivery in the Luche reduction was employed as a key step in the total synthesis of (-)-mintlactone (16).18 Utilizing Luche conditions, (+)-pulegone (14) was reduced stereoselectively to give cri-pulegol (15) in 98% yield. Ozonolysis was followed by acylation and an intramolecular Wittig-Homer reaction to complete the short, efficient synthesis of the target molecule. 

Suggest a mechanism for the following thallium(III)-mediated oxidative cyclization of the homoallylic alcohol (-)-isopulegol, which was a crucial step in a synthesis of mintlactone (Ferraz, H. M. C et al. J. Org. Chem. 2000,65,2606-2607) ... 

Allenols may be carbonylated under quite different conditions. Using Rus (CO)i 2 as the catalyst, unsaturated lactones can be synthesized efficiently." The reaction may also be extended to lactams." This cyclization, combined with an intramolecular propargylic Barbier reaction has been used in syntheses of mintlactone 4.111 from allenol 4.110 (Scheme 4.43)" " and its diastereoisomer, isomintlactone," as well as the stemona alkaloid, stemoamide 4.115 from allenol 4.113 (Scheme 4.44)," and in the skeleton of stenine." A different synthesis of stemoamide can be found in Chapter 8, Scheme 8.112. 

The alkene component of the Pauson-Khand reaction can be replaced by a carbonyl group, leading to the formation of butenolides. This reaction has proved useful in butenolide synthesis using molybdenum complexes with labile ligands. It was used in a short synthesis of an epimer of dihydrocanadensolide 7.76 from aldehyde 7.74 (Scheme 7.21). It was also used in a short synthesis of mintlactone 7.79 from citronellol 7.77 (Scheme 7.22). In an interesting transformation, citronellol 7.77 was de-methylated to the alkynol, which was oxidized to the aldehyde 7.78. Carbonylation of the aldehyde 7.78 was achieved using an activated molybdenum carbonyl species. Another synthesis of mintlactone may be found in scheme 4.43. 

Roderick W. Bates of Nanyang Technological University found (J. Org. Chem. 2008, 73, 8104), in a synthesis of (-)-Mintlactone 29, that the diastereocontroUed reductive cyclization of 27 to 28 worked best in wet DMF. Susianu Kobayashi of the Tokyo University of Science showed (Chemistry Lett. 2008, 37, 770), en route to (-)-Gleenol 32, that the Claisen rearrangement of 30 deUvered the cyclohexene 31 with high diastereocontrol. Barry B. Snider of Brandeis University prepared (J. Org. Chem. 2008, 73, 8049) (-)-Vibralactone C 36 from 33, available from o-anisic acid by the Schultz protocol. 

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