The O-Directed Free Radical Hydrostannation of Propargyloxy Dialkyl Acetylenes with Ph3SnH/cat. Et3B. A Refutal of the Stannylvinyl Cation Mechanism

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Abstract

In this Personal Account, we will give an overview of the room temperature O-directed free radical hydrostannation reaction of propargylically-oxygenated dialkyl acetylenes with Ph3SnH and catalytic Et3B/O2 in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)-pumiliotoxin B, (-)-(3R)-
inthomycin C, and (+)-acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the ISnPh3 exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O-directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo-and regio-chemical outcomes. We will also challenge and refute the recent non-directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.
Original languageEnglish
Pages (from-to)238-319
Number of pages82
JournalThe Chemical Record
Volume19
Early online date08 Nov 2018
DOIs
Publication statusEarly online date - 08 Nov 2018

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Alkynes
Acetylene
Biological Products
Free radicals
Free Radicals
Cations
Cats
Positive ions
Free radical reactions
Alkenes
Olefins
Temperature
inthomycin C
acutiphycin
pumiliotoxin B

Bibliographical note

We thank the Leverhulme Trust (Grant No RPG-2015-438) over the period 2016–2018 for their kind and most generous financial support of our recent O-directed hydrostannation work on (+)-acutiphycin, and the EPSRC via Grant GR/
N20959/01 for providing us with the initial funding to work on the total synthesis of (-)-haplosamate A over the period 2001–2003, which actually led to our development of the rt O-directed free radical hydrostannation reaction with
Ph3SnH/cat. Et3B in PhMe. We also thank Novartis for their very generous financial support of some of the work reported herein.

Keywords

  • O-Directed Free Radical Hydrostannation with Ph3SnH/cat. Et3B, Propargylically-Oxygenated Alkyl Acetylenes, Stannylvinyl Radical, b-Stannylvinyl cation, Vinylperoxy radical, Trisubstituted Stannylvinyl Radical H-Atom Abstraction, Vinylstannane isomerisation, Allylic 1,3-strain and 1,2-strain, Internal Ligand Enhanced Radicalophilicity, Ph3Sn radicals have higher electron affinity, The magnitudes of polar solvent rate accelerations observed for genuinely ionic reaction mechanisms

Cite this

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title = "The O-Directed Free Radical Hydrostannation of Propargyloxy Dialkyl Acetylenes with Ph3SnH/cat. Et3B. A Refutal of the Stannylvinyl Cation Mechanism",
abstract = "In this Personal Account, we will give an overview of the room temperature O-directed free radical hydrostannation reaction of propargylically-oxygenated dialkyl acetylenes with Ph3SnH and catalytic Et3B/O2 in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)-pumiliotoxin B, (-)-(3R)-inthomycin C, and (+)-acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the ISnPh3 exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O-directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo-and regio-chemical outcomes. We will also challenge and refute the recent non-directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.",
keywords = "O-Directed Free Radical Hydrostannation with Ph3SnH/cat. Et3B, Propargylically-Oxygenated Alkyl Acetylenes, Stannylvinyl Radical, b-Stannylvinyl cation, Vinylperoxy radical, Trisubstituted Stannylvinyl Radical H-Atom Abstraction, Vinylstannane isomerisation, Allylic 1,3-strain and 1,2-strain, Internal Ligand Enhanced Radicalophilicity, Ph3Sn radicals have higher electron affinity, The magnitudes of polar solvent rate accelerations observed for genuinely ionic reaction mechanisms",
author = "Hale, {Karl J.} and Soraya Manaviazar and Watson, {Hamish A.}",
note = "We thank the Leverhulme Trust (Grant No RPG-2015-438) over the period 2016–2018 for their kind and most generous financial support of our recent O-directed hydrostannation work on (+)-acutiphycin, and the EPSRC via Grant GR/ N20959/01 for providing us with the initial funding to work on the total synthesis of (-)-haplosamate A over the period 2001–2003, which actually led to our development of the rt O-directed free radical hydrostannation reaction with Ph3SnH/cat. Et3B in PhMe. We also thank Novartis for their very generous financial support of some of the work reported herein.",
year = "2018",
month = "11",
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language = "English",
volume = "19",
pages = "238--319",
journal = "The Chemical Record",
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T1 - The O-Directed Free Radical Hydrostannation of Propargyloxy Dialkyl Acetylenes with Ph3SnH/cat. Et3B. A Refutal of the Stannylvinyl Cation Mechanism

AU - Hale, Karl J.

AU - Manaviazar, Soraya

AU - Watson, Hamish A.

N1 - We thank the Leverhulme Trust (Grant No RPG-2015-438) over the period 2016–2018 for their kind and most generous financial support of our recent O-directed hydrostannation work on (+)-acutiphycin, and the EPSRC via Grant GR/ N20959/01 for providing us with the initial funding to work on the total synthesis of (-)-haplosamate A over the period 2001–2003, which actually led to our development of the rt O-directed free radical hydrostannation reaction with Ph3SnH/cat. Et3B in PhMe. We also thank Novartis for their very generous financial support of some of the work reported herein.

PY - 2018/11/8

Y1 - 2018/11/8

N2 - In this Personal Account, we will give an overview of the room temperature O-directed free radical hydrostannation reaction of propargylically-oxygenated dialkyl acetylenes with Ph3SnH and catalytic Et3B/O2 in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)-pumiliotoxin B, (-)-(3R)-inthomycin C, and (+)-acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the ISnPh3 exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O-directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo-and regio-chemical outcomes. We will also challenge and refute the recent non-directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.

AB - In this Personal Account, we will give an overview of the room temperature O-directed free radical hydrostannation reaction of propargylically-oxygenated dialkyl acetylenes with Ph3SnH and catalytic Et3B/O2 in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)-pumiliotoxin B, (-)-(3R)-inthomycin C, and (+)-acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the ISnPh3 exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O-directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo-and regio-chemical outcomes. We will also challenge and refute the recent non-directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.

KW - O-Directed Free Radical Hydrostannation with Ph3SnH/cat. Et3B, Propargylically-Oxygenated Alkyl Acetylenes, Stannylvinyl Radical, b-Stannylvinyl cation, Vinylperoxy radical, Trisubstituted Stannylvinyl Radical H-Atom Abstraction, Vinylstannane isomerisati

U2 - 10.1002/tcr.201700104

DO - 10.1002/tcr.201700104

M3 - Article

VL - 19

SP - 238

EP - 319

JO - The Chemical Record

JF - The Chemical Record

SN - 1528-0691

ER -