Burgess, a mild selective dehydrating reagent

Introduction to Burgess Reagent

Burgess reagent (Burgess reagent), that is, methyl N-(triethylsulfamoyl) carbamate, is a kind of internal salt of carbamate, the chemical formula is C8H18N2O4S, and the structural formula is as follows As shown in the figure, the molecular weight is 238.3, and the appearance is off-white powdery solid. This product is very sensitive to air and humidity and is easy to oxidize. It should be stored in nitrogen at low temperatures and used as soon as possible. In organic synthesis, it is soluble in most organic solvents and is an efficient dehydrating agent. Burgess reagents can efficiently dehydrate secondary and tertiary alcohols to produce alkenes. This reaction has syn-selectivity, and the selectivity of secondary alcohols is usually higher. Under milder conditions, tertiary alcohols quickly form stable tertiary carbocations and obtain E1-eliminated products. The reaction effect of the primary alcohol is not good, and it is often converted into the corresponding carbamate, which is hydrolyzed to generate primary amine compounds. In the second half of the 1980s, the Burgess reagent was also used for the dehydration of primary amines and oximes to the corresponding nitriles at room temperature, formamides to isonitriles, urea to carbodiimides, and primary nitroalkanes in Nitrile oxide is produced after treatment with Adams reagent.

 

In recent years, the biggest use of Burgess reagent is to realize the cyclodehydrogenation reaction of hydroxyamide and sulfamide to obtain the corresponding heterocyclic compound.

 

general formula

 

example

Reaction of Burgess reagent with alcohol

 

 

 

Secondary and tertiary alcohols, in aprotic solvents, give the corresponding alkenes under mild conditions. Moreover, Zaitsev alkenes are more favorably generated in the process of dehydration into alkenes involving Burgess reagent.

 

 

Dehydration of two intramolecular thiols yields thioethers.

 

 

 

The Bielawski research group also reported that under the dissolution of DMSO, secondary alcohols can react with Burgess reagents to obtain corresponding ketone compounds; and based on triethylamine salts, Burgess reagents with different ammonium salts were developed.

 

 

Primary alcohols can be reacted with Burgess reagent to obtain the corresponding carbamates.

 

Reaction of Burgess reagent with amino groups

 

 

When the substrate has sensitive and unstable groups, the conversion of amides to nitrile compounds often requires the protection of these groups in advance; while Burgess reagent can be used under very mild conditions without additional protection, one-step efficient Get converted products.

 

 

For example, when the substrate contains hydroxyl, three-membered oxygen heterocycle, Boc protecting group, etc., Burgess reagent can react with amide with high selectivity to obtain nitrile.

 

Burgess reagent and formamide to form isonitriles

 

 

Burgess reagent forms imine with urea

 

 

Burgess intramolecular formation of heterocycles

 

 

Epimerization readily occurs at the chiral center where the thiazoline is attached to amino acid C-2, so that most cyclodehydration reactions of hydroxysulfamides result in mixtures of diastereoisomers. However, under the induction of the Burgess reagent, hydroxysulfamides can give chiral monomers with high stereoselectivity in 96% yield and greater than 94% enantioselectivity.

 

 

Under the induction of the Burgess reagent, hydroxysulfamide can be converted into thiazine in high yield, which can obtain a higher yield than the Mitusnobu reaction.

 

 

A literature survey also found that Burgess reagent can be linked with polyethylene glycol to obtain a more stable polymer with higher dehydration efficiency: PEG-linked Burgess reagent.

 

 

Not long ago, Pfizer was approved to launch an oral drug, Paxlovid, which claims to be a game-changer in the fight against the new crown epidemic. Paxlovid is a compound preparation of the 3CL protease inhibitor PF-07321332 and low-dose ritonavir (Ritonavir). Phase III clinical results show that patients with mild to moderate COVID-19 who take this drug within three days of diagnosis can reduce the risk of hospitalization or death by about 89%. The Burgess reagent played a vital role in the synthesis of Paxlovid drugs.

 

 

References:
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