- Total synthesis of (+)-rubriflordilactone A
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Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium- or cobalt-catalyzed cyclizations to form the CDE rings, and converge on a late-stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products. Two in one: Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium- or cobalt-catalyzed cyclizations to converge on a late-stage synthetic intermediate. These key processes are set up through the coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that enables a broad exploration of this family of natural products, as well as synthetic analogues.
- Goh, Shermin S.,Chaubet, Guilhem,Gockel, Birgit,Cordonnier, Marie-Caroline A.,Baars, Hannah,Phillips, Andrew W.,Anderson, Edward A.
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supporting information
p. 12618 - 12621
(2015/10/28)
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- Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
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Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au-allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that Erode the efficiency of chirality transfer become competitive.
- Barker, Graeme,Johnson, David G.,Young, Paul C.,Macgregor, Stuart A.,Lee, Ai-Lan
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supporting information
p. 13748 - 13757
(2015/09/22)
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- Highly stereoselective C-C bond formation by rhodium-catalyzed tandem ylide formation/[2,3]-sigmatropic rearrangement between donor/acceptor carbenoids and chiral allylic alcohols
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The tandem ylide formation/[2,3]-sigmatropic rearrangement between donor/acceptor rhodium carbenoids and chiral allyl alcohols is a convergent C-C bond forming process, which generates two vicinal stereogenic centers. Any of the four possible stereoisomers can be selectively synthesized by appropriate combination of the chiral catalyst Rh2(DOSP)4 and the chiral alcohol.
- Li, Zhanjie,Parr, Brendan T.,Davies, Huw M. L.
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supporting information; experimental part
p. 10942 - 10946
(2012/08/07)
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- Palladium(II)-catalyzed dicarboxymethylation of chiral allylic alcohols: Chirality transfer affording optically active diesters containing three contiguous chiral centers
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This manuscript describes the extension of Stille's palladium-catalyzed olefin dicarbonylation reaction to chiral allylic alcohols with chirality transfer to afford the corresponding chiral alcohol functionalized with bis-carbomethoxy esters, containing three contiguous chiral centers, in good to excellent diastereoselectivities (78-98%).
- Hamed, Othman,Henry, Patrick M.,Becker, Daniel P.
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supporting information; experimental part
p. 3514 - 3517
(2010/09/05)
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- Synthesis of the active form of loxoprofen by using allylic substitutions in two steps
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High regioselectivity for allylic substitution of the cyclopentenyl picolinate 5 with benzylcopper reagent was attained with ZnBr2, and the finding was applied to the p-BrC6H4CH2 reagent. The cyclopentene moiety in the product was reduced to the cyclopentane, and the p-BrC6H4 was converted to the "Cu"C6H4 for the second allylic substitution with picolinate 8 to furnish the title compound after oxidative cleavage of the resulting olefin moiety.
- Hyodo, Tomonori,Kiyotsuka, Yohei,Kobayashi, Yuichi
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supporting information; experimental part
p. 1103 - 1106
(2009/07/25)
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- A synthetic approach toward nitiol: Construction of two 1,22-dihydroxynitianes
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Synthetic work toward the total synthesis of nitiol has culminated in the construction of two epimeric hydroxylated derivatives, the 1,22- dihydroxynitianes. Key stereodefining steps in the construction of the A-ring fragment (13) were the use of a siloxy-epoxide rearrangement reaction, a Pauson-Khand reaction, a Norrish 1 photochemical cleavage reaction, and a highly regio- and stereoselective hydrostannylation reaction of an ynoate. The stereochemistry of the synthetically challenging C-ring fragment (20) was established using an Ireland-Claisen reaction and a Grubbs ring-closing metathesis process as key steps. The 12-membered B-ring of the nitiane skeleton was constructed using a copper-promoted Stille cross-coupling and a Kishi-Hiyama-Nozaki carbonyl addition reaction. Unfortunately, the carbonyl addition reaction produced hydroxyl functionality that could not be selectively removed. Consequently, a synthesis of epimeric 1,22-dihydroxynitianes, which are compounds that are structural hybrids of two natural products, nitiol and variculanol, was completed.
- Wilson, Michael S.,Woo, Jacqueline C. S.,Dake, Gregory R.
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p. 4237 - 4245
(2007/10/03)
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- Palladium-catalyzed asymmetric synthesis of allylic alcohols from unsymmetrical and symmetrical racemic allylic carbonates featuring C-O-bond formation and dynamic kinetic resolution
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Described is the asymmetric synthesis of the allylic alcohols 11 (85% ee), 15 (99% ee), 17 (93% ee), 19 (61% ee), and 21 (69% ee) through a Pd-catalyzed reaction of the unsymmetrical carbonates rac-10, rac-12, rac-14, rac-16, rac-18, and rac-20, respectively, with KHCO3 and H2O in the presence of bisphosphane 6. Similarly the allylic alcohols 23 (99% ee) and 25 (97% ee) have been obtained from the symmetrical carbonates rac-22 and rac-24, respectively. Reaction of the meso-biscarbonate 26 with H2O and Pd(0)/6 afforded alcohol 27 (96% ee), which was converted to the PG building block 32. The unsaturated bisphosphane 33 showed in the synthesis of alcohols 36, 37, and 39 a similar high selectivity as 6. The formation of alcohols 11, 15, and 17 involves an efficient dynamic kinetic resolution.
- Gais, Hans-Joachim,Bondarev, Oleg,Hetzer, Ralf
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p. 6279 - 6283
(2007/10/03)
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- A chiral electrophilic selenium reagent to promote the kinetic resolution of racemic allylic alcohols
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(Chemical Equation Presented) The first example of a kinetic resolution process promoted by electrophilic selenium reagents is reported. Racemic allylic alcohols react with half equivalents of a selenenylating agent in methanol leading to the regiospecific formation of the corresponding addition products with a very high level of facial selectivity (from 95:5 to 98:2 dr). The unreacted alcohols can be recovered in an optically enriched form (from 90 to 94% ee).
- Tiecco, Marcello,Testaferri, Lorenzo,Santi, Claudio,Tomassini, Cristina,Bonini, Rosaria,Marini, Francesca,Bagnoli, Luana,Temperini, Andrea
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p. 4751 - 4753
(2007/10/03)
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- Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: Asymmetric synthesis of allylic sulfides, allylic sulfones, and allylic alcohols
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We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac-1a-c and racemic acyclic allylic carbonates rac-3aa and rac-3ba through reaction with tert-butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2-pyrimidinethiol by using N,N′-(1R,2R)-1,2-cyclohexanediylbis[2-(di-phenylphosphino)-benzamide] (BPA) as ligand. Selectivities are expressed in yields and ee values of recovered substrate and product and in selectivity factors S. The reaction of the cyclohexenyl carbonate 1a (≥99% ee) with 2-pyrimidinethiol in the presence of BPA was shown to exhibit, under the conditions used, an overall pseudo-zero order kinetics in regard to the allylic substrate. Also described are the highly selective palladium catalyzed asymmetric syntheses of the cyclic and acyclic allylic tert-butylsulfones 2aa, 2b, 2c, 2d and 4 a - c, respectively, and of the cyclic and acyclic allylic 2-pyrimidyl-, 2-pyridyl-, and 4-chlorophenylsulfides 5aa, 5b, 5ab, 6aa - ac, 6ba and 6bb, respectively, from the corresponding racemic carbonates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E-configured allylic sulfides 6aa, 6ab, 6ac and 6bb was accompanied by the formation of minor amounts of the corresponding Z isomers. The analogous synthesis of allylic tert-butylsulfides from allylic carbonates and tert-butylthiol by using BPA could not be achieved. Reaction of the cyclopentenyl esters rac-1da and rac-1db with 2-pyrimidinethiol gave the allylic sulfide 5c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac-1a and of the acyclic carbonates rac-3aa and rac-3ba with 2-pyridinethiol and lead to the formation of the sulfides 5 ab, 6 ab, and 6 bb, respectively. The low ee values may be ascribed to the operating of a "memory effect", that is, both enantiomers of the substrate give the substitution product with different enantioselectivities. However, in the reaction of the racemic carbonate rac-1 a as well as of the highly enriched enantiomers la (≥99% ee) and ent-1a (≥99% ee) with 2-pyrimidinethiol the ee values of the substrates and the substitution product remained constant until complete conversion. Similar results were obtained in the reaction of the cyclic carbonates rac-1a, ent-1a (≥99% ee) and ent-1c (≥99% ee) with lithium tert-butylsulfinate. Thus, in the case of rac-1a and 2-pyrimidinthiol and tert-butylsulfinate anion as nucleophiles the enantioselectivity of the substitution step is, under the conditions used, independent of the chirality of the substrate; this shows that no "memory effect" is operating in this case. Hydrolysis of the carbonates ent-1a-c, ent-3aa and ent-3ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9a-c (≥99% ee) and acyclic allylic alcohols 10a (≥99% ee) and 10b (99% ee), respectively.
- Gais, Hans-Joachim,Jagusch, Thomas,Spalthoff, Nicole,Gerhards, Frank,Frank, Michael,Raabe, Gerhard
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p. 4202 - 4221
(2007/10/03)
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- Palladium-catalyzed deracemization of allylic carbonates in water with formation of allylic alcohols: Hydrogen carbonate ion as nucleophile in the palladium-catalyzed allylic substitution and kinetic resolution
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The palladium-catalyzed deracemization of racemic cyclic and acyclic allylic methyl carbonates in water in the presence of N,N′-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphophino)benzamide] proceeds with high enantioselectivities to give the corresponding allylic alcohols in high yields. This deracemization involves a palladium-catalyzed allylic substitution with the in-situ-formed hydrogen carbonate ion and an irreversible decomposition of the intermediate allylic hydrogen carbonates, with formation of the corresponding allylic alcohols. The palladium-catalyzed reaction of racemic cyclic allylic acetates with potassium hydrogen carbonate in water in the presence of the chiral bisphosphane proceeds with a highly selective kinetic resolution to give the corresponding allylic alcohols and allylic acetates. Copyright
- Luessem, Bernhard J.,Gais, Hans-Joachim
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p. 6066 - 6067
(2007/10/03)
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- Succinoylamino hydroxyethylamino sulfonyl urea derivatives useful as retroviral protease inhibitors
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Succinoylamino hydroxyethylamino sulfonyl urea derivatives of the formula: wherein the substituents are as defined in the specification, are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
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Page column 26
(2010/01/30)
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- Cryptophycins from synthesis
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A cryptophycin compound is provided having the structure: Further provided are methods of producing cryptophycins by total synthesis and methods of using cryptophycins in pharmaceuticals. It is a further object of this invention to use cryptophycins to inhibit the proliferation of mammalian cells. Moreover, methods of using cryptophycins to treat neoplasia is also provided.
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- PalladiumdD-catalyzed exchange and isomerization reactions. 17. Exchange of chiral allyl alcohols with hydroxide, methoxide, and phenyl at high [Cl-]. Stereochemistry of the wacker reaction
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At high [Cl ] (> 2.0 M), PdCl42- catalyzes the exchange of chiral allylic alcohols with hydroxy, methoxy, and phenyl to give chiral allyl-substituted olefins. With unsymmetrical olefins, isomerization occurs along with exchange. The hydroxyl exchange occurs in aqueous solution while the other exchanges are carried out in methanol solution. At low [Cl-] (0.1 M) oxidation to the corresponding β-hydroxy-, methoxy-, and phenyl-substituted carbonyl compounds occurred. The absolute configurations of the oxidation and exchange products should be the same if the same mode of addition to the Pd(II)-β-complex is operative. The absolute configurations of the oxidation and exchange products for the phenylation reaction were the same, while for hydroxy and methoxy they were different. This result indicates methanol and water must have different stereochemistries of addition at high and low [Cl-]. Thus, previous studies showing anti hydroxypalladation at high [Cl-] are not valid indicators of the stereochemistry at low [Cl-]. If anti addition occurs at high [Cl-], the addition must be syn at low [Cl-].
- Hamed, Othman,Henry, Patrick M.,Thompson, Charles
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p. 7745 - 7750
(2007/10/03)
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- Synthesis of unit A of cryptophycin via a [2,3]-Wittig rearrangement
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The synthesis of unit A of the cryptophycins from (S)-trans-3-penten-2- ol and from (S)-trans-4-hexen-3-ol has been completed. The key stereodetermining step is a [2,3]-Wittig rearrangement of a propargyl ether. Elaboration of the rearrangement product was accomplished by means of a selective hydroboration-oxidation of a terminal alkyne, Horner-Emmons homologation of the derived aldehyde, followed by selective ozonolytic cleavage and Wittig olefination. This synthesis provides easy access to the series of cryptophycin analogues that incorporate a modified aromatic ring in unit A.
- Liang, Jian,Hoard, David W.,Van Khau, Vien,Martinelli, Michael J.,Moher, Eric D.,Moore, Richard E.,Tius, Marcus A.
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p. 1459 - 1463
(2007/10/03)
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- Pure Enantiomers from Retro-Diels-Alder Processes
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Diastereoselective and regioselective transformations of cycloadducts to enantiomerically pure cyclopentadienes are reported.Retro-Diels-Alder processes finally give rise to pure enantiomers in high yield.
- Beckmann, Marion,Hildebrandt, Hinrich,Winterfeldt, Ekkehard
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p. 335 - 345
(2007/10/02)
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- ACYCLIC STEREOCONTROL VIA -WITTIG REARRANGEMENT WITH HIGH ENANTIO- AND ERYTHRO-SELECTIVITY AND ITS USE IN THE CHIRAL SYNTHESIS OF INSECT PHEROMONES
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Such an asymmetric -Wittig variant that is both highly enantio- and erythro-selective is described within the context of the chiral synthesis of the insect pheromones, (3S,4S)-4-methyl-3-heptanol and (S)-4-methyl-3-heptanone.
- Sayo, Noboru,Azuma, Ken-ichi,Mikami, Koichi,Nakai, Takeshi
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p. 565 - 568
(2007/10/02)
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