Preparation of tert-butyl thio esters

Hatch, Robert P.; Weinreb, Steven M.

doi:10.1021/jo00444a039

Cited by 74 publications

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“…The resulting lactone [10] was allowed to react with (E)-iodoallyl iodide to give the desired lactone nitrile 25 in 63 % yield, after chromatographic separation from the epimeric product (13 %). Lactone nitrile 25 was converted into the corresponding hydroxy tert-butyl thioester in the presence of trimethylaluminum, [11] which in turn was transformed into ketone 26 in high yield. The carboxylic acid prepared from 26 was used for the enantioselective synthesis of diazoketone 13, which was further converted into ketone 20.…”

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confidence: 99%

A Carbonyl Ylide Cycloaddition Approach to Platensimycin

et al. 2008

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Platensimycin (1) is a novel broad-spectrum antibiotic (against Gram-positive bacteria) which was isolated from Streptomyces platensis by scientists from Merck: it inhibits bacterial growth by selectively inhibiting the condensing enzyme FabF of the bacterial fatty acid synthesis pathway. [1] Platensimycin (1) shows no cross-resistance to methicillinresistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant enterococci. As a result of its remarkable biological profile and challenging structure, platensimycin (1) has been the focus of intense synthetic activity, [2] and herein we describe the results of our recent efforts towards the synthesis of this intriguing compound.At the outset, a synthesis of the pivotal tetracyclic intermediate 2 from the cagelike ketone A was envisioned (Scheme 1). Rhodium(II)-catalyzed decomposition of a diazoketone D would lead to the formation of A and/or B through [3+2] cycloaddition [3] of the corresponding carbonyl ylide with conformations C and/or C'. This type of cycloaddition in the presence of rhodium(II) acetate is known to favor the formation of B (R = H; A/B/cyclopropanes = 6:41:36), [4] and a reversal of this product distribution seemed necessary to ensure the success of our synthetic approach.In practice, preparation of the quaternary-substituted diazoketone D was problematic.[5] After considerable experimentation, we found that the reaction sequence was successful with R = CN. Thus, diazoketone 6 was prepared from ethyl cyanoacetate (3) in a straightforward manner by sequential alkylation (Scheme 2). In the presence of rhodium(II) acetate, decomposition of diazoketone 6 proceeded smoothly to yield the cagelike ketone 8, accompanied by only a trace amount of the desired product 7, and a small amount of cyclopropane products 9. The use of rhodium(II) trifluoroacetate led to a clean conversion of 6 into 8.At first glance these results were disappointing, but we recognized that the overall cyclization-cycloaddition process was more competitive than the cyclopropanation reaction, and that the LUMO-dipole/HOMO-dipolarophile (type III) interaction [6] clearly dominated in the cycloaddition process because of the introduction of a nitrile group. The desired regioselectivity would be attained through the reversal of the olefin (dipolarophile) HOMO coefficient, for which halogen substitution emerged as an appropriate possibility. Accordingly, the halogenated substrates 10-13 were prepared from 4 for further regioselectivity studies.Rhodium(II)-catalyzed decomposition of 10 led to the relatively clean production of ketone 14 (Scheme 3). Under similar conditions, the (Z)-bromide 11 produced a relatively complex mixture from which 15 and 16 [7] were isolated in low yields. Gratifyingly, the (E)-bromide 12 was converted into Scheme 1. Retrosynthetic analysis of platensimycin (1).Scheme 2. Prototype carbonyl ylide [3+2] cycloaddition. a) NaOMe, MeCOCH 2 Cl, MeOH; b) NaH, CH 2 CHCH 2 Br, THF; c) 1 n KOH, MeOH; d) ClCO 2 iBu, TEA, diethyl ether, 0 8C; ...

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A Carbonyl Ylide Cycloaddition Approach to Platensimycin

et al. 2008

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“…In the final approach, we chose to alter the side-chain building block in order to secure selectivity for incorporation of the C-25 hydroxy group. Ethyl 6-methylhept-6-enoate [21] was transformed [22] into S-tert-butyl 6-methylhept-6-enethioate and then into ketene acetal 23 [(E)/(Z) ϭ 9:1] (Scheme 5). Conjugate addition between 23 and acceptors 5 and 8, consecutively, afforded the key intermediate 24 in 63% yield, along with a small amount of its cyclization product 25.…”

Section: Resultsmentioning

confidence: 99%

“…10 min), maintained at this temperature for a further 30 min and cooled again to 0°C. To this thus prepared Weinreb reagent, [22] ethyl 6-methylhept-5-enoate (prepared from the corresponding acid, 7.7 g, 36.0 mmol) was added dropwise, and the mixture was set aside at 0 to 5°C for 14 h. The reaction was quenched at 0°C by careful addition of water (100 mL) and then 2% HCl (50 mL). The layers were separated.…”

Section: -[(Phenylsulfonyl)methyl]-2-vinyl[13]dioxolane (13)mentioning

confidence: 99%

Diastereoselective Approaches to trans-Hydrindane Derivatives − Total Synthesis of 8-(Phenylsulfonyl)de-A,B-cholestane Precursors to 25-Hydroxyvitamin D3

Prowotorow¹,

Stepanenko²,

Wicha³

2002

Eur. J. Org. Chem.

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The total diastereoselective synthesis of the C,D rings/side chain building block for the synthesis of 1α,25-dihydroxyvitamin D 3 is described. Two tandem Mukaiyama−Michael additions involving silylated ketene acetals derived from tert-butyl 6-methylhept-5-enethioate or tert-butyl 6-methylhept-6-enethioate, 2-methylcyclopent-2-en-1-one, and 1-(phenylthio)but-3-en-2-one afforded the corresponding intermediates with the complete carbon framework of the target compound. The further transformation of these key interme-

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“…[35] This compound was transformed, without isolation, into the isopropylidene derivative 16 (Scheme 4). The product 16, purified by consecutive column chromatography and distillation, was obtained in 56% yield, 96% ee (as determined by HPLC, Chiralcel OD column).…”

Section: Synthesis Of Optically Active Side-chain Precursorsmentioning

confidence: 99%

Enantioselective Total Synthesis of a trans‐Hydrindane Rings/Side‐Chain Building‐Block of Vitamin D − Asymmetric Induction in an Acid‐Catalyzed Conjugate‐Addition Reaction

Gorobets¹,

Stepanenko²,

Wicha³

2004

Eur J Org Chem

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For the enantioselective total synthesis of 1α,25‐dihydroxyvitamin D3 (3), we have developed an enantioselective approach to the “northern” portion building‐block 8, starting from the optically active hexanoic acid derivative 44, 2‐methylcyclopent‐2‐en‐1‐one (10) and 1‐(phenylthio)but‐3‐en‐2‐one (9). The steric course of the addition reaction of homochiral (S)‐ketene acetals 28, 40, 44 and 58 with 10 was examined. We found that in the cases of 28, 44 and 40, the reactions occur with high simple and induced (facial) diastereoselectivities. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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Preparation of tert-butyl thio esters

Cited by 74 publications

References 0 publications

A Carbonyl Ylide Cycloaddition Approach to Platensimycin

A Carbonyl Ylide Cycloaddition Approach to Platensimycin

Diastereoselective Approaches to trans-Hydrindane Derivatives − Total Synthesis of 8-(Phenylsulfonyl)de-A,B-cholestane Precursors to 25-Hydroxyvitamin D3

Enantioselective Total Synthesis of a trans‐Hydrindane Rings/Side‐Chain Building‐Block of Vitamin D − Asymmetric Induction in an Acid‐Catalyzed Conjugate‐Addition Reaction

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