Publications


20
Strained Alkynes
Synthesis and Reactivity of 1-Sulfonylcyclooctatriazoles
Matthew B Williams, Ruaraidh J Wells, Alistair Boyer
Chem. Commun.
2022
58
12495
12498
.
10.1039/d2cc03648g
DOI Link
Abstract image for Synthesis and Reactivity of 1-Sulfonylcyclooctatriazoles
Strained eight-membered cyclic alkynes undergo rapid inverse electron demand cycloaddition with sulfonyl azides to give the corresponding 1-sulfonylcyclooctatriazoles in excellent yield. Treatment of these sulfonyltriazoles with a chiral rhodium(II) carboxylate catalyst prompted transannular C–H bond insertion in good yield and with excellent ee, or 1,2–H shift.
Cover for Chem. Commun. 2022 58 .

19
A Self-Assembling Flavin for Visible Photooxidation
Michele Cariello, Bart Dietrich, Lisa Thomson, Valentina Gauci, Alistair Boyer, Stephen Sproules, Graeme Cooke, Annela Seddon, Dave J Adams
Chem. Eur. J.
2022
28
49
e202201725
.
10.1002/chem.202201725
DOI Link
Abstract image for A Self-Assembling Flavin for Visible Photooxidation
We report a new flavin-based gelator which forms micellar structures at high pH and gels at low pH. This flavin can be used for the photooxidation of thiols under visible light, with the catalytic efficiency being linked to the self-assembled structures present.
Cover for Chem. Eur. J. 2022 28 49.

18
Pyrrole Synthesis
Modular Synthesis of Highly Substituted 3- Azapyrroles by Rh(II)-Catalyzed N–H Bond Insertion and Cyclodehydration
Matthew B Williams, Alistair Boyer
J. Org. Chem.
2022
87
24
16139
16156
.
10.1021/acs.joc.2c00434
DOI Link
Abstract image for Modular Synthesis of Highly Substituted 3- Azapyrroles by Rh(II)-Catalyzed N–H Bond Insertion and Cyclodehydration
This work has been cited 1 time
A modular synthesis of highly substituted 3-azapyrroles has been developed using a three-step sequence comprising copper-catalyzed alkyne–azide cycloaddition (CuAAC), N––H bond insertion, and cyclodehydration. 1-Sulfonyl-1,2,3-triazoles (1-STs) can be accessed from common alkyne and sulfonyl azide building blocks by CuAAC using CuTC. Rhodium(II)-acetate-promoted 1-ST denitrogenation results in highly electrophilic rhodium azavinyl carbenes that, here, underwent inserti on into the N–H bond of secondary α-aminoketones to form 1,2-aminoalkenes. These products were cyclized and dehydrated using BF3·OEt2 into highly substituted 3-azapyrroles. The three steps (CuAAC, N–H bond insertion, and cyclodehydration) could be telescoped into a one-pot process. The method proved to be highly efficient a nd tolerated a wide range of substituents.
Cover for J. Org. Chem. 2022 87 24.

Cover by Alistair Boyer

17
1,2–H Shift
Controlling Selectivity in the Synthesis o f Z-α,β-Unsaturated Amidines by Tuning the N-Sulfonyl Group in a Rhodium(II) Catalyzed 1,2–H Shift
Matthew L Martin, Alistair Boyer
Eur. J. Org. Chem.
2021
2021
43
5857
5861
.
10.1002/ejoc.202101235
DOI Link
Abstract image for Controlling Selectivity in the Synthesis o f <i>Z</i>-α,β-Unsaturated Amidines by Tuning the <i>N</i>-Sulfonyl Group in a Rhodium(II) Catalyzed 1,2–H Shift
This work has been cited 1 time
α,β-Unsaturated amidines can be synthesized in high yield by rhodium(II) carboxylate catalyzed 1,2–H shift following denitrogenation of α-diazo amidines. Using a large carboxylate rhodium(II) ligand and an electron-poor N-sulfonyl group results in exclusive Z-selectivity and excellent yield by suppressing side reactions involving intramolecular oxygen transfer.
Cover for Eur. J. Org. Chem. 2021 2021 43.

16
Sea Lamprey
High-Performance Liquid Chromatography Quantification of Enantiomers of a Dihydroxylated Tetrahydrofuran Natural Product
Ke Li, Skye D Fissette, Tyler J Buchinger, Zoe E Middleton, Alistair Boyer, Weiming Li
Chirality
2018
30
8
1012
1018
.
10.1002/chir.22978
DOI Link
Abstract image for High-Performance Liquid Chromatography Quantification of Enantiomers of a Dihydroxylated Tetrahydrofuran Natural Product
This work has been cited 1 time
Both enantiomers of petromyroxol are putative pheromones in sea lamprey (Petromyzon marinus). Here, we describe the separation and quantification of the petromyroxol enantiomers using high-performance liquid chromatography tandem mass spectrometry. The separation was tested on a wide range of chiral columns with normal phases, and effects of the chromatographic parameters such as mobile phase and temperature on the separation were optimized. The AD-H column showed the best separation of enantiomers with n-hexane and ethanol as the mobile phase. The enantiomers were detected by multiple reaction monitoring with a positive atmospheric-pressure chemical ionization on triple quadrupole mass spectrometer. Validation revealed that the method was specific, accurate, and precise. The validated method was applied to measure the amount of petromyroxol enantiomers in water conditioned with sea lamprey larvae, the source of the putative pheromone. This method will be applied in quantifying the natural scalemic petromyroxol mixture, enabling further investigations of a rare non-racemic enantiomeric pheromone mixture in a vertebrate species.
Cover for Chirality 2018 30 8.

15
Oxonium Ylide Formation and Rearrangement of 1-Sulfonyl-1,2,3-Triazoles
Enantioselective Synthesis of (+)-Petromyroxol, Enabled by Rhodium-Catalyzed Denitrogenation and Rearrangement of a 1-Sulfonyl-1,2,3-Triazole
Alistair Boyer
J. Org. Chem
2015
80
9
4771
4775
.
10.1021/acs.joc.5b00399
DOI Link
Abstract image for Enantioselective Synthesis of (+)-Petromyroxol, Enabled by Rhodium-Catalyzed Denitrogenation and Rearrangement of a 1-Sulfonyl-1,2,3-Triazole
This work was built on the reactivity of β-allyloxy 5-substituted triazoles [see below].
The excellent photo of the sea lamprey was taken by Ted Lawrence, Great Lakes Fishery Commission [link].
This work has been cited 26 times
Petromyroxol is a non-racemic mixture of enantiomeric oxylipids isolated from water conditioned with larval sea lamprey. The (+)-antipode exhibits interesting biological properties but only 1 mg was isolated from >100000 L of water. Recently, transition metal-catalyzed denitrogenation of 1-sulfonyl-1,2,3-triazoles has emerged as a powerful strategy for the synthesis of value-added products, including efficient diastereocontrolled construction of tetrahydrofurans. This methodology enabled the rapid development of the first synthesis of (+)-petromyroxol in 9 steps and 20% overall yield from a readily accessible starting material.
Cover for J. Org. Chem 2015 80 9.

14
Cyclopropanation
Synthesis of Cyclopropyl-Substituted Furans by Brønsted Acid Promoted Cascade Reactions
J Stephen Clark, Filippo Romiti, Kirsten F Hogg, Malai Haniti S A Hamid, Sven C Richter, Alistair Boyer, Joanna C Redman and Louis J Farrugia
Angew. Chem. Int. Ed.
2015
54
19
5744
5747
.
10.1002/anie.201500625
DOI Link
Abstract image for Synthesis of Cyclopropyl-Substituted Furans by Brønsted Acid Promoted Cascade Reactions
This work complements the sulfur-catalysed formation of furfuryl alcohols, esters and amines from ynenones [see below].
ISI Hot Paper 2015
This work has been cited 37 times
Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring various size rings and heteroatoms have be en synthesized in high yield using this mild acid-catalysed reaction.
Cover for Angew. Chem. Int. Ed. 2015 54 19.

13
Oxonium Ylide Formation and Rearrangement
Rhodium(II)-Catalyzed Stereocontrolled Synthesis of 2-Tetrasubstituted Saturated Heterocycles from 1-Sulfonyl-1,2,3-triazoles
Alistair Boyer
Org. Lett.
2014
16
22
5878
5881
.
10.1021/ol5028267
DOI Link
Abstract image for Rhodium(II)-Catalyzed Stereocontrolled Synthesis of 2-Tetrasubstituted Saturated Heterocycles from 1-Sulfonyl-1,2,3-triazoles
This work was inspired by the reativity of isomeric 5-substituted triazoles which undergo an analogous rearrangement to give dihydrofuran-3-ones [see below].
This work has been cited 58 times
Rhodium(II) acetate catalyzes the denitrogenative transformation of 4-substituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ethers and thioethers to onium ylides that undergo [2,3]-sigmatropic rearrangement to give 2-tetrasubstituted heterocycles with high yield and diastereoselectivity.
Cover for Org. Lett. 2014 16 22.

12
Oxonium Ylide Formation and Rearrangement
Rhodium(II)-Catalyzed Stereocontrolled Synthesis of Dihydrofuran-3-imines from 1-Tosyl-1,2,3-Triazoles
Alistair Boyer
Org. Lett.
2014
16
6
1660
1663
.
10.1021/ol500309x
DOI Link
Abstract image for Rhodium(II)-Catalyzed Stereocontrolled Synthesis of Dihydrofuran-3-imines from 1-Tosyl-1,2,3-Triazoles
Isomeric 4-substituted triazoles undergo an analogous rearrangement to give 2-tetrasubstituted saturated heterocycles [see above].
This method enabled a rapid synthesis of the marine natural product petromyroxol [see above].
ISI Highly Cited Paper 2014, 2015
Highlighted on the organic-chemistry.org portal [Link]
Awarded the Dave Kelly Cup for presentation of this research at the 2013 Gregynog Synthesis Workshop
This work has been cited 83 times
Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to give substituted dihydrofuran-3-imines in high yi eld and diastereoselectivity.
Cover for Org. Lett. 2014 16 6.

11
Sulfur Catalysis
Organocatalytic Synthesis of Highly Substituted Furfuryl Alcohols and Amines
J Stephen Clark, Alistair Boyer, Anthony Aimon, Paloma Engel García, David M Lindsay, Andrew D F Symington, Yves Danoy
Angew. Chem. Int. Ed.
2012
51
48
12128
12131
.
10.1002/anie.201207300
DOI Link
Abstract image for Organocatalytic Synthesis of Highly Substituted Furfuryl Alcohols and Amines
This work complements the Brønsted acid-catalysed formation of cyclopropyl-substituted furans from ynenones [see above].
Highlighted as part of the Wiley Organocatalysis Hot Topic [Link]
Highlighted in SynFacts [Abstract]
This work has been cited 57 times
Tetrahydrothiophene (THT) is an efficient organocatalyst for the synthesis of highly substituted furfuryl produc ts from readily-accessible electron-poor enynes under neutral conditions. This process is demonstrated to be applicable to a wide-range of nucleophiles and enynes; and can be incorporated in a domino organocatalysis sequence.
Cover for Angew. Chem. Int. Ed. 2012 51 48.

10
Domino Reactions
Rhodium-Catalysed Domino Enantioselective Synthesis of Bicyclo[2.2.2]lactones
Alistair Boyer, Mark Lautens
Angew. Chem. Int. Ed.
2011
50
32
7346
7349
.
10.1002/anie.201101773
DOI Link
Abstract image for Rhodium-Catalysed Domino Enantioselective Synthesis of Bicyclo[2.2.2]lactones
Featured in ChemInform 2011, 42 [Link]
This work has been cited 35 times
Once... twice... three times a catalyst! We demonstrate a novel triple domino rhodium(I)-catalysed asymme tric transformation of substituted oxabicyclic alkenes into bicycle[2.2.2]lactones. The reaction proceeds with good yields and excellent levels of stereoselectivity in each of the 16 examples studied. Mechanistic investigations suggest that this process proceeds by rhodium catalysed asymmetric ring opening, allylic alcohol isomerisation and oxidation.
Cover for Angew. Chem. Int. Ed. 2011 50 32.

9
Regiodivergent Resolution
Practical Asymmetric Synthesis of Bioactive Aminotetralins from a Racemic Precursor using a Regiodivergent Resolution
Robert Webster, Alistair Boyer, Matthew J Fleming, Mark Lautens
Org. Lett.
2010
12
23
5418
5421
.
10.1021/ol1022239
DOI Link
Abstract image for Practical Asymmetric Synthesis of Bioactive Aminotetralins from a Racemic Precursor using a Regiodivergent Resolution
Highlighted in SynFacts [Link]
This work has been cited 56 times
Catalyst-controlled asymmetric ring opening of a racemic oxabicyclic alkene leads to two readily separable regioisomeric products both in excellent ee. A cationic Rh catalyst, with added NH4BF4 to modulate reactivity, was required to obtain synthetically useful yields. The utility of each substituted aminotetralin product has been demonstrated by their conversion to different biologically relevant molecules in a highly efficient and practical manner.
Cover for Org. Lett. 2010 12 23.

8
Domino Reactions
Domino Rhodium(I)-Catalysed Reactions for the Efficient Synthesis of Substituted Benzofurans and Indoles
Alistair Boyer, Naohiro Isono, Sebastian Lackner, Mark Lautens
Tetrahedron
2010
66
33
6468
6482
.
10.1016/j.tet.2010.05.106
DOI Link
Abstract image for Domino Rhodium(I)-Catalysed Reactions for the Efficient Synthesis of Substituted Benzofurans and Indoles
Invited contribution in honour of Prof. Steven V. Ley`s receipt of the 2009 Tetrahedron Prize
Featured in ChemInform [Link]
This work has been cited 70 times
Rhodium(I) catalysts promote the transformation of o-alkynyl phenols and anilines to the corresponding benzo[b]furans and indoles. The reaction is postulated to proceed via a transient 3-rhodium heterocycle intermediate, which can be trapped with suitable electrophiles to give poly-substitut ed heterocycles. In the case of mono-substituted electron-withdrawn electrophiles, excellent yield and selectivity for conjugate addition versus Heck/Mizoroki reaction can be achie ved. In the case of 2-alkynyl pyridine electrophiles, novel 2-(benzofuran-3-yl)vinylpyridines are formed.
Cover for Tetrahedron 2010 66 33.

7
Azadirachtin
Second-Generation Synthesis of Azadirachtin: A Concise Preparation of the Propargylic Mesylate Fragment
Alistair Boyer, Gemma E Veitch, Edith Beckmann, Steven V Ley
Angew. Chem. Int. Ed.
2009
48
7
1317
1320
.
10.1002/anie.200805395
DOI Link
Abstract image for Second-Generation Synthesis of Azadirachtin: A Concise Preparation of the Propargylic Mesylate Fragment
Read the original communications, review and full paper, also see our synthesis of related natural products
Highlighted in "Classics in Total Synthesis III" [Link]
This work has been cited 18 times
A second bite of the apple: A new and highly efficient synthesis of the propargylic mesylate fragment of azadirachtin has been accomplished. An enantioselective catalytic hetero Diels-Alder reaction sets up the stereocenter at C15, which then controls the installation of the remaining functionality in a total of only 17 steps.
Cover for Angew. Chem. Int. Ed. 2009 48 7.

6
Azadirachtin
The Azadirachtin Story
Gemma E Veitch, Alistair Boyer, Steven V Ley
Angew. Chem. Int. Ed.
2008
47
49
9402
9429
.
10.1002/anie.200802675
DOI Link
Abstract image for The Azadirachtin Story
Read the original communications and full paper and also see our second generation approach and our synthesis of related natural products
Highlighted in "Classics in Total Synthesis III" [Link]
This work has been cited 67 times
Azadirachtin has been the subject of intensive research within the scientific community ever since its isolation from the neem tree in 1968. There are now over 1000 publications relating to this natural product which cover all aspects of structural, biological and synthetic studies. Herein, we describe the worldwide efforts towards the synthesis of this fascinating molecule.
Cover for Angew. Chem. Int. Ed. 2008 47 49.

cover by Matt O`Brien

5
Azadirachtin
The Synthesis of Azadirachtin: A Potent Insect Antifeedant
Steven V Ley, Antonio Abad-Somovilla, James C Anderson, Carles Ayats, Rolf Bänteli, Edith Beckmann, Alistair Boyer, Maria G Brasca, Abigail Brice, Howard B Broughton, Brenda J Burke, Ed Cleator, Donald Craig, Alastair A Denholm , Ross M Denton, Thomas Durand-Reville, Luca B Gobbi, Michael Göbel, Brian Lawrence-Gray, Robert B Grossmann, Claire E Gutteridge, Norbert Hahn, Sarah L Harding, David C Jennens, Lynn Jennens, Peter J Lovell, Helen J Lovell, Mary L de la Puente, Hartmuth C Kolb, Win-Jan Koot, Sarah L Maslen, Catherine F McCusker, Amos Mattes, Andrew R Pape, Andrea Pinto , Dinos Santafianos, James S Scott, Stephen C Smith, Andrew Q Somers, Christopher D Spilling, Frank Stelzer, Peter L Toogood, Richard M Turner, Gemma E Veitch, Anthony Wood, Cornelia Zumbrunn
Chem. Eur. J.
2008
14
34
10683
10704
.
10.1002/chem.200801103
DOI Link
Abstract image for The Synthesis of Azadirachtin: A Potent Insect Antifeedant
Read the original communications and review and also see our second generation approach and our synthesis of related natural products
VIP paper
Highlighted in "Classics in Total Synthesis III" [Link]
This work has been cited 49 times
The final chapter! We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement con structs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby th e [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.
Cover for Chem. Eur. J. 2008 14 34.

cover by Alistair Boyer

4
Clean and Efficient Synthesis of O-Silylca rbamates and Ureas in Supercritical Carbon Dioxide
Matthew J Fuchter, Catherine J Smith, Melanie W S Tsang, Alistair Boyer, Simon Saubern, John H Ryan, Andrew B Holmes
Chem. Commun.
2008
0
0
2152
2154
.
10.1039/b801537f
DOI Link
Abstract image for Clean and Efficient Synthesis of <i>O</i>-Silylca rbamates and Ureas in Supercritical Carbon Dioxide
Featured in ChemInform [Link]
This work has been cited 34 times
The synthesis of a family of O-silylcarbamates from the corresponding silylamines has been achieved simply by he ating the silylamine in supercritical carbon dioxide (scCO2), and these O-silylcarbamates have been shown to be effective precursors for the synthesis of a range of symmetrical and unsymmetrical ureas.
Cover for Chem. Commun. 2008 0 0.

3
Azadirachtin
Synthesis of Natural Products from the Indian Neem Tree Azadirachta Indica
Gemma E Veitch, Andrea Pinto, Alistair Boyer, Edith Beckmann, James C Anderson, Steven V Ley
Org. Lett.
2008
10
4
569
572
.
10.1021/ol7027898
DOI Link
Abstract image for Synthesis of Natural Products from the Indian Neem Tree <i>Azadirachta Indica</i>
Read the original communications, review and full paper and also see our second generation approach
Highlighted in "Classics in Total Synthesis III" [Link]
This work has been cited 18 times
The synthesis of five natural products isolated from the Indian neem tree Azadirachta indica, is reported from a common intermediate. The judicious choice of transacetalization conditions allows efficient access to both the azadirachtinin and the azadirachtin skeletons.
Cover for Org. Lett. 2008 10 4.

2
Azadirachtin
A Relay Route for the Synthesis of Azadirachtin
Gemma E Veitch, Edith Beckmann, Brenda J Burke, Alistair Boyer, Carles Ayats, Steven V Ley
Angew. Chem. Int. Ed.
2007
46
40
7633
7635
.
10.1002/anie.200703028
DOI Link
Abstract image for A Relay Route for the Synthesis of Azadirachtin
Read our review and full paper and also see our second generation approach and our synthesis of related natural products
Back-to-back publication [see below]
VIP paper
Highlighted in "Classics in Total Synthesis III" [Link]
SynFact of the Month [Link]
Featured in Chemistry World [Link]
Featured in Chemical and Engineering News [Link]
Featured in an Angewandte Chemie Highlight [Link]
Featured in Nature [Link]
Featured in ChemInform [Link]
This work has been cited 62 times
22 Years in the making: Azadirachtin was synthesized for the first time by a highly convergent approach, utilizing a Claisen rearrangement and a radical cyclization as key steps. End-game strategies relied on a relay-intermediate, which could be obtained by synthetic methods as well as by degradation of the natural product.
Cover for Angew. Chem. Int. Ed. 2007 46 40.

cover by Alistair Boyer

1
Azadirachtin
Synthesis of Azadirachtin: A Long but Successful Journey
Gemma E Veitch, Edith Beckmann, Brenda J Burke, Alistair Boyer, Sarah Maslen, Steven V Ley
Angew. Chem. Int. Ed.
2007
46
40
7629
7632
.
10.1002/anie.200703027
DOI Link
Abstract image for Synthesis of Azadirachtin: A Long but Successful Journey
Read our review and full paper and also see our second generation approach and our synthesis of related natural products
Back-to-back publication [see above]
VIP paper
Highlighted in "Classics in Total Synthesis III" [Link]
SynFact of the Month [Link]
Featured in Chemistry World [Link]
Featured in Chemical and Engineering News [Link]
Featured in an Angewandte Chemie Highlight [Link]
Featured in Nature [Link]
Featured in ChemInform [Link]
This work has been cited 134 times
22 Years in the making: Azadirachtin was synthesized for the first time by a highly convergent approach, utilizing a Claisen rearrangement and a radical cyclization as key steps. End-game strategies relied on a relay-intermediate, which could be obtained by synthetic methods as well as by degradation of the natural product.
Cover for Angew. Chem. Int. Ed. 2007 46 40.

cover by Alistair Boyer

Non-Refereed Contributions

2
Preparation of Horner-Wadsworth-Emmons Reagent: Methyl 2-Benzyloxycarbonylamino-2-(dimethoxyphosphinyl)-acetate
Submitters: Hiroki Azuma, Kentaro Okano, Tohru Fukuyama, Hidetoshi Tokuyama
Checkers: Alistair Boyer, Mark Lautens
Org. Synth.
2011
88
152
161
.
10.15227/orgsyn.088.0152
DOI Link
Abstract image for Preparation of Horner-Wadsworth-Emmons Reagent: Methyl 2-Benzyloxycarbonylamino-2-(dimethoxyphosphinyl)-acetate
The present procedure describes a convenient and scalable preparation of the HWE reagent that gives the (Z)-dehydroamino acid derivative, which allows facile access to Cbz-protected α-amino acid methyl esters via Rh-catalyzed enantioselective hydrogenation.
Cover for Org. Synth. 2011 88 .

1
Synthesis of Substituted Indazoles via [3+ 2] Cycloaddition of Benzyne and Diazo Compounds
Submitters: Feng Shi, Richard C Larock
Checkers: Alistair Boyer, Mark Lautens
Org. Synth.
2010
87
95
103
.
10.15227/orgsyn.087.0095
DOI Link
Abstract image for Synthesis of Substituted Indazoles via [3+ 2] Cycloaddition of Benzyne and Diazo Compounds
This work has been cited 5 times
Benzyne is a highly reactive intermediate that has attracted wide attention from synthetic organic chemists. One of the commercially available precur sors of benzyne is 2-(trimethylsilyl)phenyl trifluoromethanesulfonate which undergoes fluoride-promoted ortho-elimination to generate benzyne, mild conditions which tolerate a range of functional groups. Benzyne which is generated in this way has been shown to react with diazo compounds as 1,3-dipoles to afford substituted 1H-indazoles following a hydrogen shift.
Cover for Org. Synth. 2010 87 .