The first enantioselective syntheses of vicinal difluoropyrrolidines and the first catalytic asymmetric synthesis mediated by the C2 symmetry of a –CHFCHF– unit

Marson, Charles M.; Melling, Robert C.

doi:10.1039/a801718b

Cited by 30 publications

(26 citation statements)

References 17 publications

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“…Treatment of 1,2-diols with SF 4 [22–23], DAST [24], or deoxofluor [25] also leads to vicinal difluorides. Reaction with vicinal triflates has also been successful in some cases [7,26]. A common two-step method involves opening of an epoxide to give the corresponding fluorohydrin [27], followed by the conversion of the alcohol moiety to the fluoride [28].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane

Linclau¹,

Leung²,

Nonnenmacher³

et al. 2010

Beilstein J. Org. Chem.

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SummaryA large-scale synthesis of meso-2,3-difluoro-1,4-butanediol in 5 steps from (Z)-but-2-enediol is described. Crystallographic analysis of the diol and the corresponding benzyl ether reveals an anti conformation of the vicinal difluoride moiety. Monosilylation of the diol is high-yielding but all attempts to achieve chain extension through addition of alkyl Grignard and acetylide nucleophiles failed.

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Section: Introductionmentioning

confidence: 99%

Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane

Linclau¹,

Leung²,

Nonnenmacher³

et al. 2010

Beilstein J. Org. Chem.

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“…This was conceptually similar to the first enantioselective syntheses of vicinal N-substituted difluoropyrrolidines carried out previously. 7 In this previous work, the requisite trans-2,3-dihydroxypyrrolidine derivatives were made by reduction of diacetoxy succinimides.…”

Section: Fluorinated Pyrrolidinesmentioning

confidence: 99%

“…For example, Raines and coworkers determined that in contrast to 4R-FPro in the Yposition that enhances helix stability, 4S-FPro in the Y-position precludes triple helix formation. 25 Furthermore, replacing Pro with 4R-FPro in the X-position decreased helical stability of (4R-FPro-Pro-Gly) 7 26 and (4R-FPro-Pro-Gly]) 10 , 27 whereas 4S-FPro in the corresponding peptides increased stability. The hyperstability of the 4S-FPro and 4R-FPro-containing peptides was ascribed to stereoelectronic effects that preorganize main-chain dihedral angles to correspond to the conformation found in the triple helix.…”

Section: Fluoroproline In Peptides and Proteinsmentioning

confidence: 99%

Fluorinated Five‐Membered Nitrogen‐Containing Heterocycles

Kirk¹

2009

Fluorinated Heterocyclic Compounds

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“…Nowadays, activation of alcohols with more nucleofugic leaving groups, for example, mesylate, tosylate, or triflate, and subsequent nucleophilic S N 2 substitution by fluoride under clean inversion, have become a standard tool, particularly when fluorination with defined stereochemistry is required (Scheme 2.59).Scheme 2.59Examples of the activation-fluorination procedure for substrates with stereogenic centers[132,133]. Subsequently, the same principal method was used to obtain ethyl fluoride [131] and other alkyl fluorides.…”

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confidence: 99%

Introduction of Fluorine

Kirsch

2013

Modern Fluoroorganic Chemistry

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Shortly after their first isolation of elemental fluorine in 1886, Moissan and his co-workers treated several organic substrates with this highly reactive gas. All these experiments, either at room temperature or at liquid nitrogen temperature, resulted in sometimes violent explosions. No major defined reaction products could be isolated.A plausible, first explanation for these discouraging results was proposed by W. Bockemüller in the 1930s, on the basis of thermochemical considerations. The energy released by formation of the highly stable carbon-fluorine bonds (∼116 kcal mol −1 ) is considerably greater than the energy needed for dissociation of carbon-carbon (∼83 kcal mol −1 ) or carbon-hydrogen bonds (∼99 kcal mol −1 ) [1]. A second problem is the extremely low homolytic dissociation energy of elemental fluorine (only 37 kcal mol −1 ), which allows the ready initiation of uncontrollable radical chain reactions, even at low temperatures and in the absence of light [2].The first defined fluoroaliphatic compounds obtained by direct fluorination of organic substrates in liquid reaction media were characterized by Bockemüller [3] in the early 1930s and published with his thermochemical analysis. To control the immense reaction enthalpy, the fluorine gas was diluted with nitrogen or carbon dioxide. The organic substrate was dissolved in a cooled inert solvent, for example, CCl 4 or CF 2 Cl 2 . A similar line of work was pursued in the United States by L. A. Bigelow [4], who studied the reaction of arenes with fluorine gas.In an alternative approach, volatile organic substrates were fluorinated in the gas phase on contact with a copper mesh. This work was pioneered by K. Fredenhagen and G. Cadenbach in the early 1930s [5] and then continued by N. Fukuhara and L. A. Bigelow [6] as part of the Manhattan Project (Figure 2.1). Vapor-phase fluorination finally permitted the preparation of (relatively) defined polyfluorination products from aliphatic hydrocarbons, benzene, or acetone.A modern, improved version of this general method, the LaMar (Lagow-Margrave) process, uses a nickel reactor with different temperature zones and Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, Second Edition. Peer Kirsch.

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The first enantioselective syntheses of vicinal difluoropyrrolidines and the first catalytic asymmetric synthesis mediated by the C2 symmetry of a –CHFCHF– unit

Cited by 30 publications

References 17 publications

Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane

Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane

Fluorinated Five‐Membered Nitrogen‐Containing Heterocycles

Introduction of Fluorine

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