The Fuwa Synthesis of Didemnaketal B

Didemnaketal B 3 may be an artifact of isolation, derived from didemnaketal C, in which one of the methyl esters is instead an ethylsulfonate. Nevertheless, it is B, not C, that is a potent inhibitor of HIV protease. Haruhiko Fuwa of Tohoku University has provided (Chem. Eur. J. 2014, 20, 1848) a detailed account of the synthesis of 3, including the necessary revision of the absolute configuration of seven of the stereo­genic centers. A central feature of the modular synthesis of 3 was the cyclization of 1 to the thermodynamically most favorable diastereomer of the spiroketal 2. Three components were combined for the synthesis of 3. The upper sidechain was prepared from commercial citronellal 4. Reduction followed by protection and ozon­olysis delivered the aldehyde 5, that was carried on to the alkyne 6. Hydroiodination using the method previously reported by the authors (OHL May 30, 2011) gave 7, that was oxidized to 8 and then to the ester 9. Lactone formation by ring-closing metathesis is difficult because of the substantial preference for the extended conformation of the ester. As illustrated by the conversion of 10 to 11, this can be overcome by complexation with a Lewis acid. Conjugate addi­tion followed by phosphorylation completed the preparation of the enol phosphate 12. The third component of 3 was the lactone 15, prepared by deprotonation/kinetic protonation with 14 of 13. This was carried on to the sulfone 16, that was coupled with 17. Although the Julia–Kocienski reaction usually strongly favors the E alkene, in this case it was necessary to optimize both the base and the solvent. Sharpless asym­metric dihydroxylation followed by coupling with the enol phosphate 12 then completed the preparation of the diol 1. Addition of the ketene silyl acetal 18 to the aldehyde derived from 2 proceeded to give the undesired diastereomer 19. This was overcome by oxidation to the ketone followed by enantioselective reduction. The iodide 9 was added to the aldehyde 20 to give a 1.8:1 mixture of diastereomers, the major one of which was didemnaketal B 3. This full paper is worth reading in detail. The work reported underlines the impor­tance of powerful protocols for carbon–carbon bond formation that maintain high diastereocontrol in stereochemically complex environments.

Palladium on Layered Double Hydroxide: A Heterogeneous System for the Enol Phosphate Carbon-Oxygen Bond Activation in Aqueous Media

In this work, a new catalytic approach for the C-O activation of enol phosphates based on a palladium supported on layered double hydroxide was developed. In this case, two different ketene aminal phosphates were used as models to study the synthesis ofα-phenyl enecarbamates N-Boc/CBz under the Suzuki-Miyaura conditions. The use of an ortho-bromoaniline as precursor allowed the synthesis of the 2-phenyl indole through an arylation/Heck cyclization. Catalyst reusability enabled the synthesis of the heterocycle in moderate yields for four consecutive runs.

Efficient methods for enol phosphate synthesis using carbon-centred magnesium bases

Efficient conversion of ketones into enol phosphates under mild and accessible conditions has been realised using the developed methods with di-tert-butylmagnesium and bismesitylmagnesium. Optimisation of the quench protocol resulted in high yields of enol phosphates from a range of cyclohexanones and aryl methyl ketones.

The synthesis of the isomeric components of San Jose scale pheromone — an illustration of a stereospecific synthesis of trisubstituted alkenes

The three isomeric components of the San Jose scale pheromone, 5–7, have been synthesized from a common β-keto ester intermediate. A study of the alkylation of the dianion of methyl acetoacetate with a series of alkylating agents with the same carbon skeleton has been carried out. The trisubstituted alkenes in 5 and 6 have been synthesized stereospecifically via a copper-catalyzed coupling of a methyl Grignard reagent with the E or Z enol phosphate from the alkylated β-keto ester. In the case of the Z enol derivative, the coupling reaction was carried out on the diethyl- and diphenylphosphates, and the enol triflate. The diethyl enol phosphate gave the highest stereoselectivity. The synthetic pheromones were attractive to San Jose scale in the field.[Formula: see text]