Metallation of Phosphorylated Aliphatic Alcohols to Configurationally Stable α-Oxyalkyllithium Compounds − Use of the Phosphoryl Group as an Activating Group and Electrophile

Hammerschmidt, Friedrich; Schmidt, Susanne

doi:10.1002/1099-0690(200006)2000:12<2239::aid-ejoc2239>3.0.co;2-v

Cited by 25 publications

(12 citation statements)

References 28 publications

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“…With this information in hand, we could address the configurational stability of the intermediate a-thioalkyl carbanions of the thiophosphatemercaptophosphonate rearrangement using a chirally deuterated substrate. 9 accessed again by horse-liver alcohol dehydrogenase catalysed reduction 18 of [1-D 1 ]hexanal, was converted via tosylate to the levorotary…”

Section: Resultsmentioning

confidence: 99%

Rearrangement of lithiated S-alkyl O,O-dialkyl thiophosphates: Scope and stereochemistry of the thiophosphate–mercaptophosphonate rearrangement

Philippitsch

Hammerschmidt

2011

Org. Biomol. Chem.

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S-Alkyl O,O-dialkyl thiophosphates are prepared by alkylation of the triethylammonium salt of O,O-diisopropyl thiophosphoric acid. S-Benzyl thiophosphate was metallated at temperatures of ≥-45 °C by trityllithium and LiTMP (lithium 2,2,6,6-tetramethylpiperidide) and S-alkyl thiophosphates only by LiTMP to give dipole-stabilised carbanions which rearrange to α-mercaptophosphonates in yields of up to 45%. Metallation occurs with a high primary kinetic isotope effect (k(H)/k(D) up to ≈50). When the lithium (R)-N-isopropyl-1-phenylethylamide was used to induce the isomerisation of S-pentyl thiophosphate an α-mercaptophosphonate with an ee of 22% was isolated. (R)-S-[1-D(1)]hexyl O,O-diisopropyl thiophosphate was rearranged to a dextrorotary α-mercapto-[1-D(1)]hexylphosphonate, whose (R)-configuration was determined by chemical correlation. The thiophosphate-mercaptophosphonate rearrangement proceeds with retention of configuration.

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Section: Resultsmentioning

confidence: 99%

Rearrangement of lithiated S-alkyl O,O-dialkyl thiophosphates: Scope and stereochemistry of the thiophosphate–mercaptophosphonate rearrangement

Philippitsch

Hammerschmidt

2011

Org. Biomol. Chem.

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“…The review is focused specifically on transition metal examples, although large KIEs have also been found in main group organometallic reactions, particularly with lithium. [26][27][28][29][30][31][32][33][34][35][36][37][38] By compiling and examining this body of data, we can better categorize and understand the causes and potential uses of large isotope effects in organometallic chemistry.…”

Section: Introductionmentioning

confidence: 99%

Large Isotope Effects in Organometallic Chemistry

Truong

Miller

Maria

et al. 2021

Chemistry A European J

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The kinetic isotope effect (KIE) is key to understanding reaction mechanisms in many areas of chemistry and chemical biology, including organometallic chemistry. This ratio of rate constants, k H /k D , typically falls between 1-7. However, KIEs up to 105 have been reported, and can even be so large that reactivity with deuterium is unobserved. We collect here examples of large KIEs across organometallic chemistry, in catalytic and stoichiometric reactions, along with their mechanistic interpretations. Large KIEs occur in proton transfer reactions such as protonation of organo-metallic complexes and clusters, protonolysis of metal-carbon bonds, and dihydrogen reactivity. CÀ H activation reactions with large KIEs occur with late and early transition metals, photogenerated intermediates, and abstraction by metal-oxo complexes. We categorize the mechanistic interpretations of large KIEs into the following three types: (a) proton tunneling, (b) compound effects from multiple steps, and (c) semiclassical effects on a single step. This comprehensive collection of large KIEs in organometallics provides context for future mechanistic interpretation.

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“…The DIE decreases with increasing temperatures (1400 and 80 at −100 and −30 °C, respectively) following nonlinear Arrhenius plots typical for those processes involving tunneling. Such temperature effects have also been observed in directed lithium deprotonation in the rearrangement of organic phosphates to phosphonates where a near‐normal DIE of 6 was observed at −50 °C, which increased to ≥100 at −78 °C in α‐deprotonation 19. The large KIEs observed in some of these transformations have led to the use of deuterium as a “protecting group” in directing regioselectivity, in which it is removed at a later stage 8.…”

Section: Mechanistic Considerationsmentioning

confidence: 83%

Solvent Choice and Kinetic Isotope Effects (KIEs) Dramatically Alter Regioselectivity in the Directed ortho Metalation (DoM) of 1,5‐Dichloro‐2,4‐dimethoxybenzene

Farmer

Froese

Lee‐Ruff

et al. 2014

Chemistry A European J

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The regioselective formation of the 6-lithio derivative of 1,5-dichloro-2,4-dimethoxybenzene (i.e., 12) by directed ortho metalation (DoM) with nBuLi in THF is described. Although literature reports suggest direct deprotonation at C6, a series of time-course and labelling studies has revealed that deprotonation rather occurs exclusively at C3 followed by isomerization of the anion to C6. By contrast, when DoM was performed in Et2 O, deprotonation again occurred selectively at C3, but now no isomerization occurs, and electrophilic capture produces the regioisomer of that produced in THF. In these labeling studies, it has been found that deuterium has an enormous kinetic isotope effect (KIE) that suppresses not only the original DoM reaction at C3 when deuterium is present there, but also suppresses isomerization to C6 when the label is at that site. Remarkably, this "protecting-group" role of the deuterium is unique to THF; in ether, full deprotonation of the deuterium at C3 was observed.

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Metallation of Phosphorylated Aliphatic Alcohols to Configurationally Stable α-Oxyalkyllithium Compounds − Use of the Phosphoryl Group as an Activating Group and Electrophile

Cited by 25 publications

References 28 publications

Rearrangement of lithiated S-alkyl O,O-dialkyl thiophosphates: Scope and stereochemistry of the thiophosphate–mercaptophosphonate rearrangement

Rearrangement of lithiated S-alkyl O,O-dialkyl thiophosphates: Scope and stereochemistry of the thiophosphate–mercaptophosphonate rearrangement

Large Isotope Effects in Organometallic Chemistry

Solvent Choice and Kinetic Isotope Effects (KIEs) Dramatically Alter Regioselectivity in the Directed ortho Metalation (DoM) of 1,5‐Dichloro‐2,4‐dimethoxybenzene

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