New aspects of the Ireland and related Claisen rearrangements

Chai, Yonghai; Hong, Sang-phyo; Lindsay, Harriet A.; McFarland, Chris; McIntosh, Matthias C.

doi:10.1016/s0040-4020(02)00164-3

Cited by 193 publications

(60 citation statements)

References 113 publications

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“…Mindful of the prowess of the Claisen rearrangement [24] and recognizing that E should be accessible from a g,d-unsaturated carboxylic acid motif, ester 23 was prepared by Mitsunobu esterification [25] of known lactate-derived alcohol 22 [26] with propionic acid. Whilst this reaction proceeded well under a Figure 1.…”

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confidence: 99%

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: 99%

Total Synthesis of Berkelic Acid

Snaddon

Buchgraber

Schulthoff

et al. 2010

Chemistry A European J

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“…The fact that the unprotected phenolate site in the resulting primary product could be acylated in situ to give acetate 10 turned out to be highly advantageous for the ensuing fragment coupling (see below). 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.…”

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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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“…[1,2] The substrates for this reaction can be prepared readily and convergently by the coupling of an allylic alcohol with a carboxylic acid, and the chirality of the allylic alcohol is relayed efficiently to the carbon-carbon bond formed in the rearrangement. The absolute configuration of the two stereocenters created in the Ireland-Claisen reaction can be predicted reliably on the basis of a chairlike-transition-state model.…”

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Acyclic Stereocontrol in the Ireland–Claisen Rearrangement of α‐Branched Esters

2007

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The Ireland-Claisen rearrangement is a powerful synthetic method that has found extensive application in chemical synthesis. [1,2] The substrates for this reaction can be prepared readily and convergently by the coupling of an allylic alcohol with a carboxylic acid, and the chirality of the allylic alcohol is relayed efficiently to the carbon-carbon bond formed in the rearrangement. The absolute configuration of the two stereocenters created in the Ireland-Claisen reaction can be predicted reliably on the basis of a chairlike-transition-state model. The reaction can even be used to assemble two contiguous quaternary stereogenic centers under mild conditions. One of the current deficiencies of the method, however, is the low diastereoselectivity observed in the rearrangement of a-branched esters (Scheme 1). This shortcoming became apparent to us when we chose the IrelandClaisen rearrangement as an underlying strategy for the synthesis of the spiroimine core of gymnodimine and related natural products: [3,4] We envisaged the efficient formation of the sterically congested C7 and C22 stereocenters through the rearrangement of ester 3 (Scheme 1).For efficient chirality transfer to each of the two stereocenters that form upon the rearrangement of abranched esters such as 3, E/Z-selective enolization is required. Herein, we describe the only method developed to date that enables this type of stereoselective enolization, [5] as well as the application of this method to the Ireland-Claisen rearrangement and the enantioselective synthesis of the cyclohexene ring of gymnodimine.Our initial experiments focused on the selective production of E or Z enolates from esters in which the difference in the steric and electronic properties of the a substituents R 1 and R 2 is minimal. The chirality of lithium amides 4-6 was used to control the stereoselectivity of deprotonation (Scheme 2).[6] The starting amines were selected for their ready availability. OBrien and co-workers had described a particularly efficient synthesis of amines such as 7, which can be prepared from inexpensive styrene oxide on a large scale with no chromatographic separation. [7] Importantly, the chiral amines are not consumed in the deprotonation reaction and can be recovered in high yield by simple extraction with aqueous acid.Although the stereogenic center at the a position of the ester is destroyed upon deprotonation, it is reintroduced as a quaternary stereogenic center through the [3,3] sigmatropic shift. Ester 8 a derived from commercially available (S)-2-methylbutyric acid served as the model substrate for a preliminary study of the deprotonation step (Table 1). In a control experiment, the treatment of 8 a with LDA followed by Me 3 SiCl gave the E and Z isomers of the corresponding enolate with low selectivity (Z/E 2:1), as expected (Table 1, Scheme 1. The Ireland-Claisen rearrangement of a-branched esters as a strategy for the synthesis of the spiroimine core of gymnodimine and related natural products. PMB = p-methoxybenzyl, Pv = pivaloyl, TBDPS ...

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New aspects of the Ireland and related Claisen rearrangements

Cited by 193 publications

References 113 publications

Total Synthesis of Berkelic Acid

Total Synthesis of Berkelic Acid

A Synthesis‐Driven Structure Revision of Berkelic Acid Methyl Ester

Acyclic Stereocontrol in the Ireland–Claisen Rearrangement of α‐Branched Esters

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