Boronic Esters by One Pot Direct Arene Borylation

Title: Synthesis of Aryl and Heteroaryl Boronic Esters by One Pot Direct Arene Borylation
 

 
Start date: August 2011
Client: University of Manchester I³ Limited
Investigator Dr David Nugent
david.nugent@elucidare.co.uk

 


Introduction

Boronate esters are used extensively by the fine chemical, organic electronic, pharmaceutical and agrochemicals industries, predominantly in carbon-carbon bond forming reactions. Despite the immense importance of boronate esters to these industries a simple, robust and inexpensive method of synthesizing a range of boronate ester starting materials did not exist until now.

Researchers led by Dr Michael Ingleson have developed a novel method for synthesising a wide range of industrially important boronate esters. The technique has been shown to be simple, one pot, room temperature, high yielding, highly regioselective, functional group tolerant, robust and inexpensive. Commercially important boronate esters not accessible at a reasonable cost using traditional approaches can be produced by the process.


Markets

Boronate esters produced by this process are used widely by the fine chemical, organic electronic, pharmaceutical and agrochemical industries. This room-temperature one-pot process will augment existing cryogenic systems by enabling the production of previously unavailable chemicals whilst optimising the utilisation of and thereby financial return from historical investments.


Proposition

 

Feature Commercial benefit
Direct one-step borylation Higher yield and throughput and elimination of haloarene intermediates boosts return on investment
Good substrate scope Wide range of Suzuki Coupling building blocks can be manufactured using the same equipment and conditions (including indoles, pyrroles, indolines, thiophenes, carbazoles, triarylamines and more)
High yield No side products means isolation and purification steps are simplified
Highly regioselective Very high levels of purity even in examples where the formation of isomers is possible
Room temperature process Eliminates and the cost and complexity of installing and maintaining cryogenic reactors
Uses inexpensive common reagents Raw materials are widely available
Choice of protecting group Both pinacol and MIDA boronate esters readily accessible
Transition metal free Eliminates the need for expensive and toxic transition metals required by palladium catalysed carbon-bromine conversions
Easily scalable using existing plants Process is scalable from lab (1L) to production (>3000L) scale. No need for process re-engineering

 

Quotations from Chinese suppliers suggest the cost of raw materials required to manufacture a simple boronic ester would be approximately US$ 16.15 per kg (€ 11.69 per kg). This figure excludes work-up and MIDA or pinacol protection.

Reagent
FOB (China) per MT
Per mole
Per mole
Boron trichloride
US$ 34,920
US$ 4.09
€ 2.96
Triethylamine
US$ 2,000
US$ 0.20
€ 0.15
Aluminum chloride
US$ 1,700
US$ 0.23
€ 0.16
Total
US$ 38,620
US$ 4.52
€ 3.27
 
Boronic ester mole weight
280 g
280 g
Boronic ester cost per kg
US$ 16.15 per kg
€ 11.69 per kg

 


Documents available for download

Patent application WO 2012/025760 Process for the Borylation of Arenes and Heteroarlys

Illustrative examples of substrates produced using Manchester method: Updated 15 March 2012

Licensing Opportunity: Boronic esters by one-pot direct arene borylation

Simple inexpensive boron electrophiles for direct arene borylation, The Royal Society of Chemistry, Chem. Commun., 2011

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Pinacol Boronates by Direct Arene Borylation with Borenium Cations, Angewandte Chemie International Edition, Vol. 50, Issue 9, pages 2102–2106, February 25, 2011

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