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Regioselectivity and Stereochemistry of Hydroboration02:36

Regioselectivity and Stereochemistry of Hydroboration

A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation02:47

Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation

Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
Hydroboration-Oxidation of Alkenes03:08

Hydroboration-Oxidation of Alkenes

In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation02:17

Reduction of Alkenes: Asymmetric Catalytic Hydrogenation

Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Amides to Carboxylic Acids: Hydrolysis01:28

Amides to Carboxylic Acids: Hydrolysis

Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration02:34

Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration

The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.

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A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
07:06

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis

Published on: February 16, 2020

Hidroboración asimétrica catalítica eficiente dirigida por amida y dirigida por amida.

Sean M Smith1, Nathan C Thacker, James M Takacs

  • 1Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, USA.

Journal of the American Chemical Society
|March 4, 2008
PubMed
Resumen

Este estudio demuestra una hidroboración altamente regioselectiva y enantioselectiva catalizada por el rodio de amidas acíclicas beta, gamma insaturadas utilizando ligandos quirales de fosfito y pinacolborano (PinBH). El método produce eficientemente amidas beta-hidroxi valiosas con excelente enantiopuridad.

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Área de la Ciencia:

  • Química orgánica es la química orgánica.
  • La catálisis de la catálisis.
  • Síntesis asimétrica de síntesis.

Sus antecedentes:

  • Las amidas acíclicas beta y gamma insaturadas son versátiles intermediarios sintéticos.
  • El desarrollo de métodos enantioselectivos para su funcionalización es crucial para la síntesis de moléculas quirales.
  • Las reacciones catalizadas por el rodio ofrecen potentes herramientas para transformaciones selectivas.

Objetivo del estudio:

  • Desarrollar una hidroboración catalizada por el rodio altamente regioselectiva y enantioselectiva de amidas acíclicas beta, gamma insaturadas.
  • Identificar los ligandos quirales eficientes y las condiciones de reacción para esta transformación.
  • Para demostrar la síntesis de valiosos productos de beta-hidroxiamida.

Principales métodos:

  • Hidroboración catalizada por el rodio utilizando Rh ((nbd) 2BF4 y ligandos quirales de monofosfito o fosforamidita.
  • Exploración del alcance del sustrato que incluye alquenos disubstituidos y trisubstituidos.
  • Oxidación de los ésteres intermedios de boronato a las beta-hidroxiamidas.

Principales resultados:

  • Se ha logrado una alta regioselectividad (>95%) y enantioselectividad (93-99% ee) en la hidroboración de varias amidas acíclicas beta, gamma insaturadas.
  • Identificó el fosforamidito 4 derivado de BINOL y el fosfito 5c derivado de TADDOL como ligandos altamente efectivos.
  • Se ha demostrado una síntesis eficiente de beta-hidroxiamidas, ejemplificada por la fenilamida de ácido (S) -3-hidroxihexanoico en un rendimiento del 80% y un 99% ee.
  • Se encontró que las N-fenil amidas y el pinacolborano (PinBH) son más eficientes que sus análogos y el catecolborano, respectivamente.
  • Se observó una catálisis efectiva con una carga moderada del catalizador (0,5 mol %) y temperaturas entre 25-40 °C.

Conclusiones:

  • Se ha establecido un protocolo de hidroboración catalizado por rodio robusto y eficiente para las amidas acíclicas beta, gamma insaturadas.
  • El método desarrollado proporciona acceso a las amidas beta-hidroxi enriquecidas enantioméricamente con alto regio- y estereocontrol.
  • El uso de simples ligandos quirales de fosfito ofrece un enfoque práctico para la síntesis asimétrica.