Mild Oxidation Method without Water
Propose a Mechanism.
Where did this Reaction come from?
Condensed Synthesis Overview of (+)-Cortistatin A from Hajos-Parrish Ketone.
The overall synthesis of (+)-Cortistatin A started with an enantiomerically pure Hajos-Parrish ketone undergoing key reactions such as diastereoselective hydrogenation, Rubottom oxidation, the Dess-Martin oxidation and other types of reactions to eventually form the target compound (+)-Cortistatin A. This occurs over a 26 step synthesis pathway.
How is Dess-Martin Oxidation used?
Dess-Martin Oxidation Usage in Intermediate Formation.
This reaction showing the Dess-Martin oxidation of this alcohol intermediate was part of the overall synthesis pathway of the formation of (+)-Cortistatin A. (+)-Cortistatin A is a potent inhibitor of endothelial cell proliferation. This compound was synthesized through the conversion of an enantiomerically pure Hajos-Parrish ketone to a known enone and then to a silyloxydiene intermediate. 2
Identify the Right Reagents
Identify the Key Features of the Compound
Identifying Side Chains and Alcohol Conversion
Tracking Side Chains and Alcohol Conversion.
In Dess-Martin oxidation of primary alcohols, the process involves assigning one side chain (R) to understand the reaction better.
Variations on how Aldehydes may appear.
They may be differently presented in different questions as shown in the image, however they are the same structure.
Reactive Intermediate Formation
Formation of Reactive Intermediate.
Alcohol group (-OH) performs a nucleophilic attack on the iodine center of the DMP molecule, forming a complex with the iodine. Acetoxy group is expelled and acts as a good leaving group that leaves with an extra electron pair.
See the Shortform Version of this Step
Stabilization with Acetate Ion
Charge Stabilization using a Acetate Ion.
The newly formed intermediate is stabilized by the previously expelled OAc (Acetoxy) group (now an acetate ion).
See the Shortform Version of this Step
Product Formation and Acetic Acid Recovery
Acetic Acid Recovery and Product Formation.
Acetic acid is recovered, and the intermediate undergoes proton transfer initiated by another acetate ion to form the aldehyde product.
See the Shortform Version of this Step
Overview of Final Products
Overall Products recovered post-oxidation.
Formation of the aldehyde product and iodinane and acetic acid as by-products.
See the Shortform Version of the Products
Propose a Mechanism for this Reaction.
Where did this Reaction come from?
Synthesis Overview of the Total Synthesis of Ingenol.
𝛽-ketoester (2) is subjected through a 32 steps synthesis path to form the target compound Ingenol (1). 3
How is Dess-Martin Oxidation used?
Dess-Martin Oxidation Usage in Intermediate Formation.
This reaction showing the Dess-Martin oxidation of the alcohol intermediate was part of the overall synthesis pathway of the formation of Ingenol. Ingenol is the parent compound of several naturally occurring ingenanes with varied peripheral functionalities. These ingenanes display a range of interesting biological profiles, from tumor-promoting to anti-leukemic and anti-HIV activities. 3
Identify the Right Reagents
Identify the Key Features of the Compound
Identifying Side Chains and Alcohol Conversion
Tracking Side Chains and Alcohol Conversion in Dess-Martin Oxidation
In Dess-Martin oxidation of secondary alcohols, the colored side chains represent R groups that remain unchanged during the reaction.
Reactive Intermediate Formation
Formation of Reactive Intermediate with Secondary Alcohol
The mechanism follows the same steps as the primary alcohol oxidation but includes an additional side chain.
See the Shortform Version of this Step
Stabilization with Acetate Ion
Stabilization of Reactive Intermediate Using an Acetate Ion
The intermediate is stabilized by the expelled OAc group (Acetoxy group).The expelled acetoxy group becomes an acetate ion (CH₃COO⁻).
See the Shortform Version of this Step
Ketone Formation and Acetic Acid Recovery
Formation of Ketone Product and Recovery of Acetic Acid.
Acetic acid is recovered, and the intermediate becomes a ketone after proton transfer.
See the Shortform Version of this Step
Final Overall Products
Final Products of Dess-Martin Oxidation with Secondary Alcohol
The products are similar to those in the primary alcohol oxidation mechanism, with the key difference being the formation of a ketone instead of an aldehyde.
See the Shortform Version of the Products
Reveal the Answer.
This compound was a secondary alcohol which was oxidized to a ketone.
The alcohol intermediate was oxidized to a ketone using Dess-Martin periodinane (DMP) in dichloromethane (DCM) in room temperature (RT) for 1 minute.
Where did this Reaction come from?
Completion of the synthesis of Clostrubin.
The completion of the Clostrubin (1) synthesis using a stabilized diazo compound and a thioester with several conditions. This caused the formation of a metal-carbenoid intermediate, which was reduced to an episulfide intermediate to a tetrasubstituted olefin, followed by ultraviolet light-induced electrocyclization and final global deprotection, which yielded the desired natural product efficiently.
How is Dess-Martin Oxidation used?
Reveal the Answer.
Identify the necessary side chain and product.
This compound was a primary alcohol.
Start by identifying the non-alcohol portion of the molecule and determine the product.
Perform the Mechanism for Primary Alcohols
Reconstruct the final product.
Where did this Reaction come from?
Completion of the synthesis of (+)-Preussin.
Scheme for the enantioselective total synthesis of (+)-Preussin (1) from protected L-N-benzoylphenylalaninol (6) over 10 steps.
How is Dess-Martin Oxidation used?
Full Primary Mechanism
Full Secondary Mechanism