Showing papers by "Leo A. Paquette published in 2010"
3 citations
TL;DR: In this paper, a sequence was developed for enhancing the level of functionality in both of these sectors within the central medium-sized ring without incurring ring closure, as a consequence of the close proximity of the olefinic and carbonyl centers in ketone 4.
Abstract: As a consequence of the close proximity of the olefinic and carbonyl centers in ketone 4, the molecule participates readily in transannular reactions. Sequences have been developed for enhancing the level of functionality in both of these sectors within the central medium-sized ring without incurring ring closure
TL;DR: In this article, the stereochemical course of the 1,2-addition of several allyl metal reagents and of the Normant Grignard [ClMgO(CH2)3MgCl] to 2-methoxycyclohexanone and tetrahydrofuranspiro-(2-cyclopropyl-hexanones) has been determined, and a 4-tert-butyl group is present to serve as a conformational anchor.
Abstract: The stereochemical course of the 1,2-addition of several allylmetal reagents and of the Normant Grignard [ClMgO(CH2)3MgCl] to 2-methoxycyclohexanone and tetrahydrofuranspiro-(2-cyclohexanone) has been determined. In four of the six substrates examined, a 4-tert-butyl group is present to serve as a conformational anchor. The neighboring methoxyl substituent is shown to be capable of engaging effectively in chelation, although special circumstances can dictate otherwise. Experiments involving the allylindium reagent as the nucleophile in aqueous solution reveal that the presence of water does not inhibit the operation of chelation control, which often exceeds that attainable with the corresponding magnesium, cerium, and chromium reagents in anhydrous media by significant margins. The extent to which cooperation between the α-oxygen atom and control of π-facial nucleophilic attack reaches a maximum (>97:3) is when the system is conformationally rigid and the 2-methoxy and 4-tert-butyl groups are both oriente...
TL;DR: In this paper, a photooxygenation chemistry of 3-substituted furans to construct the zaragozic acid/squalestatin backbone is described. But this work was performed without chelation control to give a 1:1 mixture of diastereomeric alcohols.
Abstract: A practical application of the photooxygenation chemistry of 3-substituted furans to construction of the zaragozic acid/squalestatin backbone is described. Although addition of 3-lithiofuran to the tartrate-derived aldehyde 7 proceeds without chelation control to give a 1:1 mixture of diastereomeric alcohols 8, it is demonstrated initially that ready conversion to the polyfunctional intermediate 10 is possible by sequential treatment of 9 with singlet oxygen, sodium borohydride, and triisopropylsilyl triflate. The actual enantiocontrolled route consisted of oxidation of 8 to the ketone and Wittig olefination of the latter in advance of asymmetric dihydroxylation with AD-mix-beta. Once this series of transformations had been accomplished, formation of the target product 30 was realized by an entirely comparable photooxygenation.
TL;DR: The feasibility of the titled reactions for the rapid, enantioselective synthesis of cis-tricyclo precursors to taxusin and taxol has been examined in this paper.
Abstract: The feasibility of the titled reactions for the rapid, enantioselective synthesis of cis-tricyclo[9.3.1.03,8]pentadecane precursors to taxusin and taxol has been examined. The catalysts most well suited to inducing the appropriate 1,2-shifts have been identified. To a great extent, the rearrangement products are formed as a direct consequence of appropriate structural features (kinetic phenomenon) and strain minimization (thermodynamic driving force). Complementary MM2 calculations of the global minimum in each series provided indications that were completely in line with the experimental observations. Sophisticated NMR studies and X-ray crystallographic determinations were coordinated to remove any ambiguity of product structure and solid-state conformation.
TL;DR: The reaction of open-chain or cyclic α-diketones with specific ω-alkenyl organometallics leads readily under the proper conditions to 1,2-diols bonded to terminal olefinic chains as mentioned in this paper.
Abstract: The reaction of open-chain or cyclic α-diketones with specific ω-alkenyl organometallics leads readily under the proper conditions to 1,2-diols bonded to terminal olefinic chains. With 1-phenyl-1,2-propanedione, biacetyl, and cyclohexane-1,2-dione, allylindation in aqueous THF proceeds readily at both adjacent carbonyls. For cyclododecane-1,2-dione, recourse must be made to allylmagnesium bromide for completing the second-stage condensation. Grignard reagents have also served well as reactants for biacetyl monoadducts. In contrast, monoallylated camphorquinone is reluctant to couple to Grignard reagents and reacts only when Barbier-type alkyllithium reactions are applied. The ring closing metatheses of these products have been examined. Where six-membered ring formation operates, cyclization can be performed directly on diols. When larger rings are involved, the diols will react only if structural preorganization capable of facilitating mutual approach of the two double bonds is at play. For this purpose,...
TL;DR: In this article, a practical route for the total synthesis of 8,9secokaurene diterpenes is described, where the central step is the [3.3]sigmatropic rearrangement of spirocyclic intermediates such as 35, 40, and 41.
Abstract: A practical route for the total synthesis of 8,9-secokaurene diterpenes is described. The central step is the [3.3]sigmatropic rearrangement of spirocyclic intermediates such as 35, 40, and 41. All three compounds must necessarily respond identically to properly install the absolute configuration of the bridgehead methine carbon. The total synthesis of (−)-O-methylshikoccin (2b) was realized in 8% overall yield from the Wieland−Miescher ketone 9. Its naturally occurring epoxide 47 was prepared with comparable efficiency. The preparative route developed herein should provide a general entry into this important class of diterpenoids.
TL;DR: Taxusin and taxol as discussed by the authors have been shown to have a remarkable capacity for stabilizing microtubule assembly and deterring cell division, which has attracted unrivaled attention.
Abstract: Our involvement with the de novo acquisition of taxusin (1) and taxol (2) has been fueled in large part by the enchanting structural features of these molecules and the much heralded antitumor efficacy of 2, particularly in patients beset with refractory ovarian, breast, and lung cancers.1 In combination with the unusual mode of action of 2, which exhibits a remarkable capacity for stabilizing microtubule assembly and deterring cell division,2 the intrinsically exciting promise shown by taxol for benefiting human health has commanded unrivaled attention.
TL;DR: The structural designation A originally made by Sharma and Alam to sclerophytin A was considered to be ambiguous and so notably strained relative to B that the latter was targeted for de novo synthesis (Scheme 1) as discussed by the authors.
Abstract: The structural designation A originally made by Sharma and Alam to sclerophytin A was considered to be ambiguous and so notably strained relative to B that the latter was targeted for de novo synthesis (Scheme 1). Our two successful routes began with (5S)-(d-menthyloxy)-2(5H)-furanone and involved the application of cycloaddition, Claisen ring expansion, transannular oxymercuration, and 1,2-carbonyl transposition tactics to arrive at B. It was immediately apparent from polarity considerations and spectroscopic data that the antileukemic marine metabolite in question was in need of more deep-seated structural revision. Following close re-examination of an acquired authentic sample by advanced NMR techniques, the strong inference was made that sclerophytin A actually lacked a second oxygen bridge and was in reality the triol C. This conclusion was unequivocally confirmed by diverting an advanced intermediate generated earlier into a short sequence beginning with regiocontrolled dihydroxylation and terminating with configurational inversion at the secondary carbinol center. The status of other members of this series is also presented. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:311–320, 2001.
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TL;DR: In this paper, the potent immunosuppressive agent (-)-sanglifehrin A (5), initially discovered in a soil sample from Malawi, has been synthesized in a highly convergent and stereocontrolled manner.
Abstract: The potent immunosuppressive agent (-)-sanglifehrin A (5), initially discovered in a soil sample from Malawi, has been synthesized in a highly convergent and stereocontrolled manner. The enantioselective approach relies on initial construction of the iodovinyl carboxylic acid 14, which is coupled to tripeptide 59 in advance of a key macrolactonization step that generates 61a. An alternative protocol that involves the linkage of 14 to 46 for possible construction of the large ring failed due to an inability to bring about a corresponding macrolactamization maneuver. An efficient means for elaborating the C26-N42 spirolactam western sector of 5 is also detailed. This requisite fragment was assembled through the proper adaptation of consecutive aldol tactics for construction of the nine stereogenic centers, six of which are contiguous. The first aldol process consisted of the tin triflate-mediated reaction of the aldehyde derived from 72 with enantiopure ketone 73 to generate the syn C36-C37 relationship resident in 75. Once the conversion of 75 to 78 had been completed, the attachment to ketone 66 was effected with (+)-DIPCl, thereby setting the C33-C34 relationship as anti. Once functional group modifications had given rise to 62, spirolactamization was achieved to deliver predominantly 94, thereby setting the stage for the acquisition of vinyl stannane 13 and its subsequent palladium-catalyzed Stille coupling to 61b. Controlled acidic hydrolysis completed the synthesis of 5. Other important features of the present route are addressed where relevant.