- Electrophilic Iron Catalyst Paired with a Lithium Cation Enables Selective Functionalization of Non-Activated Aliphatic C?H Bonds via Metallocarbene Intermediates
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Combining an electrophilic iron complex [Fe(Fpda)(THF)]2 (3) [Fpda=N,N′-bis(pentafluorophenyl)-o-phenylenediamide] with the pre-activation of α-alkyl-substituted α-diazoesters reagents by LiAl(ORF)4 [ORF=(OC(CF3)3] provides unprecedented access to selective iron-catalyzed intramolecular functionalization of strong alkyl C(sp3)?H bonds. Reactions occur at 25 °C via α-alkyl-metallocarbene intermediates, and with activity/selectivity levels similar to those of rhodium carboxylate catalysts. Mechanistic investigations reveal a crucial role of the lithium cation in the rate-determining formation of the electrophilic iron-carbene intermediate, which then proceeds by concerted insertion into the C?H bond.
- Hernán-Gómez, Alberto,Rodríguez, Mònica,Parella, Teodor,Costas, Miquel
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p. 13904 - 13911
(2019/08/30)
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- Control Mechanism for cis Double-Bond Formation by Polyunsaturated Fatty-Acid Synthases
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Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) are essential fatty acids for humans. Some microorganisms biosynthesize these PUFAs through PUFA synthases composed of four subunits with multiple catalytic domains. These PUFA synthases each create a specific PUFA without undesirable byproducts, even though the multiple catalytic domains in each large subunit are very similar. However, the detailed biosynthetic pathways and mechanisms for controlling final-product profiles are still obscure. In this study, the FabA-type dehydratase domain (DHFabA) in the C-subunit and the polyketide synthase-type dehydratase domain (DHPKS) in the B-subunit of ARA synthase were revealed to be essential for ARA biosynthesis by in vivo gene exchange assays. Furthermore, in vitro analysis with truncated recombinant enzymes and C4- to C8-acyl ACP substrates showed that ARA and EPA synthases utilized two types of DH domains, DHPKS and DHFabA, depending on the carbon-chain length, to introduce either saturation or cis double bonds to growing acyl chains.
- Hayashi, Shohei,Satoh, Yasuharu,Ogasawara, Yasushi,Maruyama, Chitose,Hamano, Yoshimitsu,Ujihara, Tetsuro,Dairi, Tohru
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p. 2326 - 2330
(2019/02/01)
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- Regio- and Stereocontrol in the Reactions of α-Halo-β,γ-enoates and α- O -Phosphono-β,γ-enenitriles with Organocuprates
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The reactions of (Z)- and (E)-ethyl 2-chloro-3-octenoate (4a and 17) and (E)- and (Z)-diethyl (1-cyano-2-heptenyl)phosphate (21a and 21b) with organocuprates were investigated as potential substrates for preparing γ-substituted α,β-enoates and enenitriles. In these copper-mediated allylic substitution reactions, the Z-isomer 4a displayed complete regio- and stereoselectivity (i.e., E:Z), while the regio- and stereoselectivity for E-isomer 17 varied as a function of solvent, cuprate reagent, transferable ligand, and cuprate counterion (e.g., Li+ vs MgX+). Excellent selectivities could be achieved with 17 and nBuCuCNLi in Et2O. Conditions for improved selectivities in the reactions of allylic cyanophosphates over those previously reported were found. A series of relative rate and competition experiments was performed, and the degree of regio- and stereoselectivity for each system was rationalized in the light of the current mechanistic understanding of cuprate-mediated allylic substitution reactions.
- Dieter, R. Karl,Picado, Alfredo
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p. 11125 - 11138
(2015/02/19)
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- Wittig reactions in water media employing stabilized ylides with aldehydes. Synthesis of α,β-unsaturated esters from mixing aldehydes, α-bromoesters, and Ph3P in aqueous NaHCO3
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(Chemical Equation Presented) Water is demonstrated to be an effective medium for the Wittig reaction over a wide range of stabilized ylides and aldehydes. Despite sometimes poor solubility of the reactants, good chemical yields normally ranging from 80 to 98% and high E-selectivities (up to 99%) are achieved, and the rate of the reactions in water is unexpectedly accelerated. The efficiency of water as a medium in the Wittig reaction is compared to conventional organic solvents ranging from carbon tetrachloride to methanol. The aqueous Wittig reaction works best when large hydrophobic entities are present, such as aromatic, heterocyclic aromatic carboxaldehydes, and long-chain aliphatic aldehydes with triphenylphosphoranes. The E/Z-isomeric ratio of the Wittig products appears dependent on the electron-accepting/donating capacity and the location of the substituents present in the aromatic ring. The effect of additives, such as benzoic acid, LiCl, and sodium dodecyl sulfate (SDS), on the Wittig reaction has been explored. The Wittig reaction can also be conducted in the presence of acidic entities, such as phenols and carboxylic acids. In addition, large α-substituents in the aliphatic aldehydes do not jeopardize the reaction. It is also demonstrated that hydrates of aldehydes can be used directly in the aqueous Wittig reaction as substrates. The scope of the aqueous Wittig reaction is extended to 24 examples of one-pot mixtures of Ph3P, α-bromoesters, and aldehydes in sodium bicarbonate solution (at 20°C for 40 min to 3 h) to provide Wittig products of up to 99% yield and up to 98% E-selectivity. Since water is inexpensive, extremely easy to handle, and represents no environmental concerns, it should be considered a possible medium for new organic reactions.
- El-Batta, Amer,Jiang, Changchun,Zhao, Wen,Anness, Robert,Cooksy, Andrew L.,Bergdahl, Mikael
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p. 5244 - 5259
(2008/02/07)
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- A convenient one-pot PCC oxidation-Wittig reaction of alcohols
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A simple one-pot process for the PCC oxidation of alcohols followed by in situ trapping of the aldehyde with a Wittig reagent is described.
- Bressette, Andrew R.,Glover IV, Louis C.
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p. 738 - 740
(2007/10/03)
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- Ulongapeptin, a cytotoxic cyclic depsipeptide from a Palauan marine cyanobacterium Lyngbya sp.
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Ulongapeptin (1), a cyclic depsipeptide, was isolated from a Palauan marine cyanobacterium Lyngbya sp. The gross structure was elucidated through one-dimensional TOCSY experiments and other spectroscopic techniques. The absolute and relative stereochemistry of the β-amino acid, 3-amino-2-methyl-7-octynoic acid (AMO), in 1 was determined by synthesis of the saturated α-alkyl-β-amino acid and Marfey's analysis of the acid hydrolysate of tetrahydro-1. Ulongapeptin (1) was cytotoxic against KB cells at an IC50 value of 0.63 μM.
- Williams, Philip G.,Yoshida, Wesley Y.,Quon, Michael K.,Moore, Richard E.,Paul, Valerie J.
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p. 651 - 654
(2007/10/03)
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- Highly cis-selective Horner-Wadsworth-Emmons (HWE) reaction of methyl bis(2,4-difluorophenyl) phosphonoacetate
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Of the previously reported Homer-Wadsworth-Emmons (HWE) reaction, the olefination of methyl bis(2,4-difluorophenyl)phosphonoacetate (1a) with various aldehydes gave unsaturated esters in the highest cis-selectivity.
- Kokin, Keisuke,Motoyoshiya, Jiro,Hayashi, Sadao,Aoyama, Hiromu
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p. 2387 - 2392
(2007/10/03)
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- STEREOSPECIFIC CROSS-COUPLING REACTIONS OF 3-ARYLSULFINYLPROPENOATES WITH ORGANOMETALLIC REAGENTS
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(E)- or (Z)-3-arylsulfinylpropenoates have been reacted with several organometallic reagents.Grignard reagents were found to promote only the complete substitution of the arylsulfinyl group in good yields (up to 92percent).The reaction followed a stereochemical course of retention of configuration with high values of stereospecificity (up to 99percent) in most cases.The observation made are discussed in the light of current views concerning nucleophilic substitution at a vinyl carbon atom.The addition-elimination pathway is considered valid, whereas a route involving the formation of a sulfurane as an intermediate, followed by a ligand coupling, is considered less likely.
- Cardellicchio, Cosimo,Cicciomessere, Angela Rosa,Naso, Francesco,Tortorella, Paolo
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p. 555 - 558
(2007/10/03)
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- AN IMPROVED PROCEDURE FOR THE TWO CARBON HOMOLOGATION OF ESTERS TO α,β-UNSATURATED ESTERS
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Treatment of esters with diisobutylaluminium hydride (DIBAL) in the presence of lithio-trialkylphosphonoacetate results in improved yields of the homologated α,β-unsaturated esters.The problematic overreduction, which has previously observed in the half reduction of esters using DIBAL, is minimal (3percent) under these conditions.
- Takacs, James M.,Helle, Mark A.,Seely, Franklin L.
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p. 1257 - 1260
(2007/10/02)
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- ETUDE DE LA REACTION CHLOROCARBENE-ACETALS DE CETENES. II. STEREOSELECTIVITE DE LA REACTION.
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We have studied the stereoselectivity of the addition reaction of chloro and chloromethyl carbenoids with ketene alkylsilyl acetals.The best stereoselectivity was generally observed with the dimethyl tertiobutylsilyloxy group.With the chlorocarbenoid, using an E ketene acetal we obtained in majority (ca. 80percent) an E α,β-ethylenic ester and using a Z ketene acetal we obtained in majority (ca. 70percent) a Z α,β-ethylenic ester.In the case of the chloromethyl carbenoid the two ketene acetal isomers led to the same α-substituted α,β-ethylenic ester (ca. 88percent of selectivity).With the chlorophenylcarbenoid, formation of ca. 90percent of E α phenyl α,β-ethylenic ester is observed.
- Rousseau, G.,Slougui, N.
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p. 2653 - 2664
(2007/10/02)
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