Mild alcohol methylation procedure for the synthesis of polyoxygenated natural products. Applications to the synthesis of lonomycin A

Evans, David A.; Ratz, Andrew M.; Huff, Bret E.; Sheppard, George S.

doi:10.1016/0040-4039(94)85352-5

Cited by 69 publications

(45 citation statements)

References 8 publications

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“…The hydroxyl group of 10 was protected as a DMPM ether in 11 through a sequence involving ester reduction with LiAlH 4 , conversion of the 1,3-diol to the 3,4-dimethoxybenzylidene acetal, and regioselective acetal reductive opening with DIBAL. The primary alcohol of 11 was oxidized under Swern conditions,21 and the resulting aldehyde was treated with 3 equiv of γ-siloxy allylstannane 12 22a and BF 3 -OEt 2 in CH 2 Cl 2 at −78 °C22b to afford the 3,4- syn -4,5- syn -homoallylic alcohol with >95:5 dr. Methylation of the alcohol (MeOTf, 2,6-di- tert -butyl-4-methylpyridine)23 and oxidative cleavage of the olefin provided aldehyde 14 , which in turn was converted to allyl ester 15 via chlorite oxidation to the carboxylic acid24 and esterification with allyl alcohol under Mitsunobu conditions 25…”

Section: Resultsmentioning

confidence: 99%

Total Syntheses of (+)-Tedanolide and (+)-13-Deoxytedanolide

et al. 2008

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Convergent total syntheses of the potent cytotoxins (+)-tedanolide (1) and (+)-13-deoxytedanolide (2) are described. The carbon framework of these compounds was assembled via a stereoselective aldol reaction that unifies the C(1)-C(12) ketone fragment 5 with a C(13)-C(23) aldehyde fragment 6 (for 13-deoxytedanolide) or 52 (for tedanolide). Multiple obstacles were encountered en route to (+)-1 and (+)-2 that required very careful selection and orchestration of the stereochemistry and functionality of key intermediates. Chief among these issues was the remarkable stability and lack of reactivity of hemiketals 33b and 34 that prevented the tedanolide synthesis from being completed from aldol 4. Key to the successful completion of the tedanolide synthesis was the observation that the 13-deoxy hemiketal 36 could be oxidized to C(11,15)-diketone 38 en route to 13-deoxytedanolide. This led to the decision to pursue the tedanolide synthesis via C(15)-(S)-epimers, since this stereochemical change would destabilize the hemiketal that plagued the attempted synthesis of tedanolide via C(15)-(R) intermediates. However, use of C(15)-(S) configured intermediates required that the side chain epoxide be introduced very late in the synthesis, owing to the ease with which the C(15)-(S)-OH cyclized onto the epoxide of intermediate 50.

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Section: Resultsmentioning

confidence: 99%

Total Syntheses of (+)-Tedanolide and (+)-13-Deoxytedanolide

et al. 2008

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“…The use of a large excess of enolate 34 was found to be crucial for the effectiveness of the reaction, as lower amounts of 34 resulted in incomplete conversion of aldehyde 21 . Due to the large excess of 34 , the aldol product could only be obtained as a 1:9 mixture with the starting glycolyl imide; however, the latter could be readily removed by FC after methylation of the free hydroxyl group with Meerwein salt (Me 3 OBF 4 ) 33. Selective cleavage of the THP‐acetal with MgBr 2 34 followed by removal of the chiral auxiliary with LiOH/H 2 O 2 then furnished seco‐acid 20 in 51 % overall yield for the 4‐step sequence from aldehyde .…”

Section: Resultsmentioning

confidence: 99%

Elucidation of the miniemulsion stabilization mechanism and polymerization kinetics

Anderson

Sudol

El‐Aasser

2003

J of Applied Polymer Sci

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Styrene/hexadecane miniemulsions were polymerized at 50°C using a redox initiator. The miniemulsions and their corresponding latexes were characterized in terms of size, polymerization rate, and surface properties. The resulting data were analyzed to elucidate the miniemulsion stabilization and polymerization mechanisms. It was found that the free surfactant concentration exceeded the critical micelle concentration when large amounts of surfactant (60 mM sodium lauryl sulfate) were used, resulting in simultaneous micellar and droplet nucleation. Most surfactant was on the surface of the droplets (85%) or particles (95%). The fractional surface coverage was proportional to the surfactant concentration to the 0.55 power. Using a particle diameter equation, the number of particles was calculated to be proportional to the surfactant concentration to the 1.35 power. Through direct particle size measurements, a power of 1.38 was confirmed. The rate of polymerization was determined by reaction calorimetry to be proportional to the number of particles to the 0.59 power, in contrast to classical Smith-Ewart kinetics for conventional emulsions (1.0 power). The average number of radicals per particle was estimated from the rate and number data, and varied with the particle diameter to the 0.97 power. The observed kinetic dependencies were validated through an extension of Smith-Ewart theory.

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“…Evans et al used the same reaction conditions for ether formation in the synthesis of lonomycin A [8]. The hindered alcohol in a cyclic polyether was efficiently methylated with trimethyloxonium tetrafluoroborate and Proton Sponge (1) (5 equiv.…”

Section: Ether Synthesis By O-alkylationmentioning

confidence: 92%

Related Organocatalysts (1): A Proton Sponge

Nagasawa

2009

Superbases for Organic Synthesis

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Mild alcohol methylation procedure for the synthesis of polyoxygenated natural products. Applications to the synthesis of lonomycin A

Cited by 69 publications

References 8 publications

Total Syntheses of (+)-Tedanolide and (+)-13-Deoxytedanolide

Total Syntheses of (+)-Tedanolide and (+)-13-Deoxytedanolide

Elucidation of the miniemulsion stabilization mechanism and polymerization kinetics

Related Organocatalysts (1): A Proton Sponge

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