Highly enantioselective sequential Claisen–Ireland/metathesis: synthesis of cycloalkenes bearing two contiguous highly functionalized asymmetric centres

Français, Antoine; Bedel, Olivier; Picoul, Willy; Meddour, Abdelkrim; Courtieu, Jacques; Haudrechy, Arnaud

doi:10.1016/j.tetasy.2004.12.029

Cited by 18 publications

(17 citation statements)

References 27 publications

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“…In our initial Communication, a standard Ireland-Claisen rearrangement of the silylketene acetal derived from ent-23 (KHMDS, TMSCl, toluene) [27,28] provided, upon methylation, anti-24 in good yield and acceptable diastereoselectivity (d.r. 10.2:1).…”

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confidence: 97%

Total Synthesis of Berkelic Acid

Snaddon

Buchgraber

Schulthoff

et al. 2010

Chemistry A European J

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A productive total synthesis of both enantiomers of berkelic acid (1) is outlined that takes the structure revision of this bioactive fungal metabolite previously proposed by our group into account. The successful route relies on a fully optimized triple-deprotection/1,4-addition/spiroacetalization cascade reaction sequence, which delivers the tetracyclic core 32 of the target as a single isomer in excellent yield. The required cyclization precursor 31 is assembled from the polysubstituted benzaldehyde derivative 20 and methyl ketone 25 by an aldol condensation, in which the acetyl residue in 20 transforms from a passive protecting group into an active participant. Access to fragment 25 takes advantage of the Collum-Godenschwager variant of the ester enolate Claisen rearrangement, which clearly surpasses the classical Ireland-Claisen procedure in terms of diastereoselectivity. Although it is possible to elaborate 32 into the target without any additional manipulations of protecting groups, a short detour consisting in the conversion of the phenolic -OH into the corresponding TBS-ether is beneficial. It tempers the sensitivity of the compound toward oxidation and hence improves the efficiency and reliability of the final stages. Orthogonal ester groups for the benzoate and the aliphatic carboxylate terminus of the side chain secure an efficient liberation of free berkelic acid in the final step of the route.

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confidence: 97%

Total Synthesis of Berkelic Acid

Snaddon

Buchgraber

Schulthoff

et al. 2010

Chemistry A European J

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“…An Ireland-Claisen rearrangement [11] of ester 13, resulting from the lactate-derived alcohol 12 [12] and propionyl chloride, furnished the second building block (Scheme 3). The reaction was best performed with KHMDS in toluene, [13] and delivered the required anti-configured ester 15 in good yield and high diastereoselectivity (d.r. = 10.2:1, 91 % ee).…”

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confidence: 99%

“…While an in-depth discussion must await a future full paper, a few comments are necessary. First, compound 19 -which features the structure attributed to berkelic acid -is the only isomer in which the 13 C NMR signal of the methyl branch C25 (d = 14.38 ppm) deviates considerably from the chemical shift of this group in the natural product (d = 11.9 ppm; Scheme 4). NOESY data as well as the solid-state structure of this compound (Figure 1) show an unfavorable syn-periplanar arrangement between the methyl substituent and the C16 methylene group of the adjacent tetrahydropyran ring (torsion angle C25-C18-C17-C16: 138).…”

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confidence: 99%

A Synthesis‐Driven Structure Revision of Berkelic Acid Methyl Ester

et al. 2008

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A subtle difference: A single step suffices to transform a linear precursor into the chromane spiroketal core of the metalloproteinase-3 inhibitor berkelic acid by an acid-catalyzed deprotection/Michael addition/acetalization cascade. This efficient route resulted from the realization that the originally proposed structure is neither thermodynamically nor kinetically favored and has led to revision of the structure

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“…74 Substrates 114,116,118, and 120 were subjected to olefin metathesis using 2.5 mol % of 3 in the presence of dichloromethane to furnish the corresponding carbocycles, including fused bicyclic (119) and spirocyclic (121) systems, in upward of 86% yield. Haudrechy and coworkers applied a similar approach to synthesize a number of highly functionalized carbocycles, 75 and recently Sutherland and co-workers used an analogous aza-Claisen/ring-closing metathesis route in the preparation of functionalized carbocyclic amides (not shown Martin and co-workers applied a ring-closing metathesis strategy in the synthesis of medium-size carbocycles fused to butyrolactones. 77 Fused butyrolactones are ubiquitous in nature and play an important role in the structural integrity and biological activity of many natural products.…”

Section: Six-membered Ringsmentioning

confidence: 99%

Large‐Ring Carbocycles

2010

Name Reactions for Carbocyclic Ring Formations

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Highly enantioselective sequential Claisen–Ireland/metathesis: synthesis of cycloalkenes bearing two contiguous highly functionalized asymmetric centres

Cited by 18 publications

References 27 publications

Total Synthesis of Berkelic Acid

Total Synthesis of Berkelic Acid

A Synthesis‐Driven Structure Revision of Berkelic Acid Methyl Ester

Large‐Ring Carbocycles

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