Selection of boron reagents for Suzuki–Miyaura coupling

 Suzuki–Miyaura (SM) cross-coupling is arguably the most widely-applied transition metal catalysed carbon–carbon bond forming reaction to date. Its success originates from a combination of exceptionally mild and functional group tolerant reaction conditions, with a relatively stable, readily prepared and generally environmentally benign organoboron reagent. A variety of such reagents have been developed for the process, with properties that have been tailored for application under specific SM coupling conditions. This review analyses the seven main classes of boron reagent that have been developed. The general physical and chemical properties of each class of reagent are evaluated with special emphasis on the currently understood mechanisms of transmetalation. The methods to prepare each reagent are outlined, followed by example applications in SM coupling.
http://pubs.rsc.org/en/content/articlehtml/2014/cs/c3cs60197h

Review Article

Selection of boron reagents for Suzuki–Miyaura coupling

Alastair J. J. Lennox^a and   Guy C. Lloyd-Jones*^a  

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*

Corresponding authors

^a

School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK

Chem. Soc. Rev., 2014,43, 412-443

DOI: 10.1039/C3CS60197H
Received 12 Jun 2013, First published online 03 Oct 2013 

 http://pubs.rsc.org/en/Content/ArticleLanding/2014/CS/c3cs60197h?utm_source=toc-alert&utm_medium=email&utm_campaign=pub-cs-vol-43-issue-1#!divAbstract
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 http://pubs.rsc.org/en/content/articlehtml/2014/cs/c3cs60197h
 DOI: 10.1039/C3CS60197H (Review Article) Chem. Soc. Rev. , 2014, 43, 412-443

Recent advances on diversity oriented heterocycle synthesis via multicomponent tandem reactions based on A3 coupling

ARKIVOC 2014 Part (i): Special Issue 'Reviews and Accounts', PG 1-20
Recent advances on diversity oriented heterocycle synthesis via multicomponent tandem reactions based on A³ coupling (14-8183LR) [pp. 1-20]
Yunyun Liu, a,b
a  Key Laboratory of Functional Small Organic Molecule, Ministry of Education, 
Jiangxi Normal University, Nanchang 330022, P. R. China 
b College of Chemistry and Chemical Engineering, Jiangxi Normal University, 

Nanchang 330022, P. R. China 

Full Text: PDF (235K)http://www.arkat-usa.org/get-file/48824/

A3 coupling reactions are the reactions between aldehydes, amines and alkynes, which yield
propargylamine derivatives under various catalyst conditions. By making use of the versatile
reactivity of propargylamines, tandem reactions initiated by the functional group(s) in the in situ
generated propargylamines constitute one of the most important applications of A3
 couplings.
These tandem reactions are especially useful for the synthesis of heterocyclic compounds. In this
review, the progress on multicomponent tandem reactions based on A3
 coupling is summarized.

Conclusions and Outlook

During the last decade, A3
 coupling reaction has evolved to a classical three-component protocol
for accessing various propargylamines. Numerous papers have been published on the
investigation of this synthetic method and spectacular advances on A3
 coupling reactions have
been witnessed in terms of green catalyst system, asymmetric catalysis etc. which also promoted
this coupling protocol as the most preferred option for propargylamine synthesis. From the
perspective of application, the propargylamines possessed broad spectrum of diversity andreactivity, and these compounds could serve as main building blocks in the synthesis of many
organic small molecules. From the perspective of atom economics, devising tandem reactions
based on key transformation of A3
 coupling for the synthesis of more complex and structurally
diverse heterocyclic products in one-pot represent a promising direction in modern organic
synthesis. As introduced in the contents, many elegant results have already been reported on this
area. On the other hand, at current state, this kind of tandem reactions were mainly performed by
using the second functional group in aldehyde, amine or alkyne to initiate subsequent
transformations on propargylamine intermediates, although some reactions using additional
components such as carbon dioxide to design tandem synthesis of heterocyclic products have
also been reported, this kind of examples are still rather rare. Thus, deeper and broader explore is
still demanding since using additional substrates for reactions is theoretically able to provide
considerably higher diversity both in reactions and corresponding products. In addition, versions
of asymmetric catalysis on traditional A3
 coupling have already been accomplished with nice
results, while asymmetric catalysis protocols of A3
 coupling-based tandem synthesis of
heterocycles kept unexplored, more systematic and advanced approaches of asymmetrical
catalysis on these tandem reactions are expected in future.



CHINA FLAG

Some of the thousands of life-sizeTerracotta Warriors of the Qin Dynasty, ca. 210 BCE

The Great Wall of China was built by several dynasties over two thousand years to protect the sedentary agricultural regions of the Chinese interior from incursions by nomadic pastoralists of the northern steppes

Detail from Along the River During the Qingming Festival, a 12th-century painting showing everyday life in the Song Dynasty's capital city, Bianjing (today's Kaifeng)

Shanghai skyline

The Great Hall of the People in Beijing, where the National People's Congress convenes

BEIJING

An Expeditious Route to Chiral δ-Aminoesters and Piperidones

The addition of malonate esters to α,β-unsaturated N-sulfonyl imines has been reported by a team from Spain
Read more

A Simple Route to Chiral Synthesis

Asymmetric conjugate addition reactions of alkenylaluminums to enones
Read more

Conversion of sugars to ethylene glycol with nickel tungsten carbide in a fed-batch reactor: high productivity and reaction network elucidation

Green Chem., 2013, Advance Article
DOI: 10.1039/C3GC41431K, Paper

Roselinde Ooms, Michiel Dusselier, Jan A. Geboers, Beau Op de Beeck, Rick Verhaeven,
Elena Gobechiya, Johan A. Martens, Andreas Redl, Bert F. Sels
Fed-batch reactor technology was used for the highly productive conversion of
concentrated sugar solutions into ethylene glycol using bifunctional nickel tungsten
carbide catalysts.

Conversion of sugars to ethylene glycol with nickel tungsten carbide

 in a fed-batch reactor: high productivity and reaction 

network elucidation

 

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 Bifunctional nickel tungsten carbide catalysis was used for the conversion of aqueous sugar

 solutions into short-chain polyols such as ethylene glycol. It is shown that very concentrated sugar 

solutions, viz. up to 0.2 kg L⁻¹, can be converted without loss of ethylene glycol selectivity 

by gradually feeding the sugar solution. Detailed investigation of the reaction network

 shows that, under the applied reaction conditions, glucose is converted via a retro-aldol

 reaction into glycol aldehyde, which is further transformed into ethylene glycol by hydrogenation. 

The main byproducts are sorbitol, erythritol, glycerol and 1,2-propanediol. 

They are formed through a series of unwanted side reactions including 

hydrogenation, isomerisation, hydrogenolysis and dehydration. 

Hydrogenolysis of sorbitol is only a minor source of ethylene glycol. To assess the 

relevance of the fed-batch system in biomass conversions, both the influence of the

 catalyst composition and the reactor setup parameters like temperature, pressure 

and glucose addition rate were optimized, culminating in ethylene glycol yields up to 66% and

 separately, volume productivities of nearly 300 g_EG L⁻¹ h⁻¹.

Synthesize 7-azanorbornane on an industrial scale

Synthesize 7-azanorbornane on an industrial scale

Patent Number:	US 8404865
Title:	Process for preparing azabicyclic compounds
Inventor(s):	Ambhaikar, Narendra Bhalchandra; Bear, Brian Richard; Fanning, Lev T. D.; Hughes, Robert; Littler, Benjamin
Patent Assignee(s):	Vertex Pharmaceuticals Incorporated, USA
Source:	U.S. Pat. Appl. Publ., 8pp. CODEN: USXXCO
Language:	English
Abstract:The present invention relates to a process for prepg. azabicyclic compds. that are useful intermediates for synthesizing pharmaceutical compds. or salts thereof.  Thus, azabicyclo[2.2.1]heptane hydrochloride (I·HCl) was prepd. from trans-4-aminocyclohexanol via N-protection with Boc2O in CH2Cl2 contg. Et3N; mesylation with MsCl in CH2Cl2 contg. Et3N; N-deprotection with CF3CO2H; cyclization with aq. NaOH; and treatment with http://www.google.com.mx/patents/US8404865 view patent 7-azabicyclo[2.2.1]heptanes are useful intermediates in the synthesis of pharmaceutical compounds and salts thereof. For example, see U.S. Pat. Nos. 6,117,889 and 6,060,473, each of which is hereby incorporated by reference in its entirety

 Despite the title of N. B. Ambhaikar and co-inventors’ patent, “Process for preparing azabicyclic compounds”, it only describes a process for preparing 7-azanorbornane (5) and its HCl salt (6). The inventors state that compound 5 is an intermediate in the synthesis of pharmaceutical compounds, but they do not mention any.

The patent’s examples describe the preparation of 5 and its precursors on a kilogram scale. The first step is protecting the amino group in 1 by converting it to tert-butoxycarbonyl (BOC) derivative 2 with the anhydride (BOC)2O in the presence of Na2CO3. The product is isolated in 88.8% yield. The reaction can also be carried out with K2CO3, but the yield is not reported.

In the second step, 2 is treated with methanesulfonyl chloride (MsCl) in the presence of Et3N to form methanesulfonate 3 in 96.6% isolated yield. In step three, the BOC group is removed by adding CF3CO2H in two batches. The product is amine salt 4. The recovered salt contains excess CF3CO2H; and as a result, the yield appears to be >100%.

In the final stage, the CF3CO2H salt is treated with NaOH to cyclize it to the desired compound. Azanorbornane 5 is recovered by fractional distillation; treating the fractions with concd HCl gives hydrochloride salt 6. The salt is recovered as a solid, dried, and recrystallized from MeOH and MeOH–THF. Although the examples contain significant detail, the product’s final yield and purity are not reported.

The process is an efficient method for preparing 7-azanorbornane and its salt. It is clearly suitable for large-scale production. (Vertex Pharmaceuticals [Cambridge, MA]. US Patent 8,404,865, March 26, 2013; Keith Turner)

NMR

 7-azanorbornane HCl salt (6). 

¹HNMR (DMSO-d⁶) ppm 8.02-8.04 (d); 7.23-7.31 (m); 4.59 (s); 3.31 (s); 2.51-3.3 (m); 1.63-1.75 (m); 1.45-1.62 (m).

In one aspect, the invention includes a process for preparing Compound 7-azanorbornane

PL IGNORE NUMBER 7

• • or a pharmaceutically acceptable salt thereof, comprising contacting trans-4-aminocyclohexanol with Boc anhydride to produce a compound of formula A

• • contacting a compound of formula A with methanesulfonic acid to produce a compound of formula B

• • contacting a compound of formula B with trifluoroacetic acid to produce a compound of formula C

• • contacting a compound of formula C with hydroxide to produce a compound of formula 

In some embodiments, the invention includes a method of producing a compound of formula 7-azanorbornane Hydrocloride salt

• • The TFA salt of trans-4-aminocyclohexylmethanesulfonate (200 g, 650.9 mmol) was introduced into a 3-necked flask followed by the addition of water (2.200 L, 11 vol). NaOH (78.11 g, 1.953 mol, 3 eq) was slowly added, keeping the temperature of the reaction mixture below 25° C. and the mixture was stirred overnight. DCM (1.4 L, 7 vol) was then added and the mixture stirred, and the organic layer was separated. The aqueous layer was then extracted a second time with DCM (1.4 L, 7 vol), and the DCM layers were combined. HCl (108.5 mL, 12M, 1.3020 mol, 2 eq) was then added, the mixture was stirred for 30 min and then concentrated on a rotary evaporator to dryness. Acetonitrile (10 vol) was added and the mixture concentrated. This was repeated 3 times until all trace water was azeotropically removed, to provide 7-azabicyclo[2.2.1]heptane hydrochloride. The crude product was recrystallized from acetonitrile (10 vol) to provide 7-azabicyclo[2.2.1]heptane hydrochloride as a colorless crystalline solid.