Straightforward synthesis of 1,2,3-tricarbonyl systems

Total Syntheses of Epothilones A and B

“…This enolate underwent successful union with aldehyde 45 to produce a mixture of C3 epimers with the desired compound 52 predominating. A particularly interesting and efficient method for conducting the coupling of 49 and 45 involved merger of the two units in a “Barbier” sense …”

“…That such a prospect could be even considered, arose from the fact that the gem -dimethyl substitution at C4 blocks the possibility of deprotonation of the aldehyde function. It will be recalled that earlier, in converting compound 45 to 52 (Scheme ), we had exploited this principle by conducting an ester enolate aldol coupling under Barbier-type conditions . Here, we would be drawing from the same concept in a macroaldolization step.…”

Oxidation of β-Ketoamides: The Synthesis of Vicinal Tricarbonyl Amides

“…13,15 Third, oxidative cleavage of the CC, CN, CS, CP, and CI double bonds of some α-methylene-functionalized βdicarbonyl compounds such as α-diazo-β-dicarbonyls can also afford VTCs. 2,10,16 This involves a two-step procedure consisting of functionalizing the central carbon followed by oxidation with suitable reagents such as t BuOCl/HCO 2 H, 6 2iodoxybenzoic acid (IBX), 2 O 2 or O 3 , 17 Oxone, 18 DMP, 19 and Received: December 22, 2016 Published: February 23, 2017 NaIO 4 (Figure 2, path c). 20 Although numerous, efficient approaches have been established, a literature review showed a limited number of existing works addressing the systematic construction of vicinal tricarbonyl amides (VTAs) directly using β-ketoamides through a one-step reaction, 12 except for several examples using the strategy of α-methylene-functionalized βketoamides by multistep reactions.…”

“…First, starting with α-unfunctionalized β-dicarbonyl compounds has been the most efficient way to obtain VTCs in the presence of various oxidation catalytic systems, including DDQ/TEMPO, CAN, m -CPBA/Cu­(OAc) 2 , Dess–Martin periodinane (DMP), SeO 2 , and 1 O 2 /Bu 4 NF, over the past several decades (Figure , path a). Second, the conversion of α-mono- and disubstituted β-dicarbonyl derivatives to the desired VTCs constitutes another important route (Figure , path b). , Third, oxidative cleavage of the CC, CN, CS, CP, and CI double bonds of some α-methylene-functionalized β-dicarbonyl compounds such as α-diazo-β-dicarbonyls can also afford VTCs. ,, This involves a two-step procedure consisting of functionalizing the central carbon followed by oxidation with suitable reagents such as t BuOCl/HCO 2 H, 2-iodoxybenzoic acid (IBX), O 2 or O 3 , Oxone, DMP, and NaIO 4 (Figure , path c) . Although numerous, efficient approaches have been established, a literature review showed a limited number of existing works addressing the systematic construction of vicinal tricarbonyl amides (VTAs) directly using β-ketoamides through a one-step reaction, except for several examples using the strategy of α-methylene-functionalized β-ketoamides by multistep reactions. ,− While this work was being prepared, Zhang and co-workers reported a complementary approach to VTCs by an iodosobenzene-mediated direct oxidation of the β-dicarbonyl C–H activation/annulation cascade using electrophilic α-halo and α-pseudohalo ketones assisted by Fe­(NO 3 ) 3 ·9H 2 O under mild and environmentally friendly conditions.…”

Total synthesis of rapamycin via a novel titanium-mediated aldol macrocyclization reaction

“…ref 24) with NaIO< inMeOH/H20 produced 4 in 93% yield. Scheme I Scheme IP " (a) LDA, THF, -78 °C;2,57%.…”