1 3
Theor Chem Acc (2016) 135:13
DOI 10.1007/s00214-015-1768-6
REGULAR ARTICLE
Deviation from the anti-Markovnikov rule: a computational study
of the regio- and stereoselectivity of diene hydroboration reactions
Laurence Hamdan
1 · Khaled Abdel-Maksoud
1 · Riya Radia
1 · Janine Boodram
1 ·
Kwan Y. Man
1 · Iain McGregor
1 · Catherine Munteanu
1 · Kishan Muthu
1 ·
Jannat Poddar
1 · Joanna Roberts
1 · Stephanie Sadler
1 · Nabeela Siddiqi
1 ·
Sianne Tam
1 · Anna Andreou
2 · Oren A. Scherman
2 · Edina Rosta
1
Received: 17 August 2015 / Accepted: 20 November 2015 / Published online: 26 December 2015
© The Author(s) 2015 . This article is published with open access at Springerlink.com
not follow the anti-Markovnikov rule. We proceed to show
that in addition to the polarity of the double bonds within a
molecule, in this case, the conjugation with the allyl double
bond and the specifi c geometric features of the cyclohexane ring were key stabilizing factors for the unexpected
transition state preference, resulting in a regioselectivity
that is in quantitative agreement with previous experimental data. Our results further indicated that Re-face attacks
and steric factors due to substituents of the substrate infl uenced mainly the stereoselective outcome of the reaction,
also affecting the pathways available to proceed through to
complete the hydroboration process.
Keywords Hydroboration · Anti-Markovnikov rule ·
Markovnikov rule · 11B NMR · Lewis acid–base ·
Frustrated Lewis pair
1 Introduction
Hydroboration is one of the most central reactions pertaining to boron chemistry, due to its involvement in a wide
array of chemical synthesis applications [ 1 – 5 ]. Hydroboration of alkenes has great importance because of the wide
variety of uses of the resulting organoboranes, such as in
Suzuki cross-coupling reactions and aldol condensation
reactions [ 6 – 8 ]. Compared with other intermediate compounds, organoboranes are readily prepared from alkenes
and alkynes with various structures, giving them their great
applicability in organic synthesis [ 6 , 9 – 11 ]. Furthermore,
the highly stereo- and regioselective nature of hydroboration products has lent themselves to applications in pharmaceuticals [ 12 ], as well in the reduction of environmental CO 2 [ 13 ] and in the polymerization of propylene into
polypropylene [ 14 ]. Despite the relevance of the direct
Abstract Hydroboration and subsequent use of boron
compounds in novel organic synthesis have been fl ourishing in recent years largely due to its amiability in producing asymmetric stereo- and regioselective products. Direct
products of diene hydroboration, however, have received
little attention, with most substrates being assumed to produce the anti-Markovnikov product expected from textbook
organic chemistry understanding. Previous experimental
studies have observed the presence of a plethora of hydroboration products, and a signifi cant progress has been
made in assigning species to experimental data—though
often with contradicting results. This study has used a
computational approach employing quantum chemical
calculations to determine atomic charges of cyclic and
acyclic dienes and correlate these with calculated activation energy barriers in order to predict the regio- and stereoselective outcome of hydroboration reactions. Results
indicated a strong correlation between the most polarized
atomic charges of double-bonded carbons and the lowest
energy transition states as expected. Intriguingly, we identifi ed 1,3-cyclohexadiene as the main example that does
Published as part of the special collection of articles “Festschrift
in honour of P. R. Surjan”.
Electronic supplementary material The online version of this
article (doi: 10.1007/s00214-015-1768-6 ) contains supplementary
material, which is available to authorized users.
* Edina Rosta
edina.rosta@kcl.ac.uk
1
Department of Chemistry , King’s College London ,
London SE1 1DB , UK
2
Melville Laboratory for Polymer Synthesis, Department
of Chemistry , University of Cambridge , Lensfi eld Road ,
Cambridge CB2 1EW , UK
235
Reprinted from the journal
Theor Chem Acc (2016) 135:13
DOI 10.1007/s00214-015-1768-6
REGULAR ARTICLE
Deviation from the anti-Markovnikov rule: a computational study
of the regio- and stereoselectivity of diene hydroboration reactions
Laurence Hamdan
1 · Khaled Abdel-Maksoud
1 · Riya Radia
1 · Janine Boodram
1 ·
Kwan Y. Man
1 · Iain McGregor
1 · Catherine Munteanu
1 · Kishan Muthu
1 ·
Jannat Poddar
1 · Joanna Roberts
1 · Stephanie Sadler
1 · Nabeela Siddiqi
1 ·
Sianne Tam
1 · Anna Andreou
2 · Oren A. Scherman
2 · Edina Rosta
1
Received: 17 August 2015 / Accepted: 20 November 2015 / Published online: 26 December 2015
© The Author(s) 2015 . This article is published with open access at Springerlink.com
not follow the anti-Markovnikov rule. We proceed to show
that in addition to the polarity of the double bonds within a
molecule, in this case, the conjugation with the allyl double
bond and the specifi c geometric features of the cyclohexane ring were key stabilizing factors for the unexpected
transition state preference, resulting in a regioselectivity
that is in quantitative agreement with previous experimental data. Our results further indicated that Re-face attacks
and steric factors due to substituents of the substrate infl uenced mainly the stereoselective outcome of the reaction,
also affecting the pathways available to proceed through to
complete the hydroboration process.
Keywords Hydroboration · Anti-Markovnikov rule ·
Markovnikov rule · 11B NMR · Lewis acid–base ·
Frustrated Lewis pair
1 Introduction
Hydroboration is one of the most central reactions pertaining to boron chemistry, due to its involvement in a wide
array of chemical synthesis applications [ 1 – 5 ]. Hydroboration of alkenes has great importance because of the wide
variety of uses of the resulting organoboranes, such as in
Suzuki cross-coupling reactions and aldol condensation
reactions [ 6 – 8 ]. Compared with other intermediate compounds, organoboranes are readily prepared from alkenes
and alkynes with various structures, giving them their great
applicability in organic synthesis [ 6 , 9 – 11 ]. Furthermore,
the highly stereo- and regioselective nature of hydroboration products has lent themselves to applications in pharmaceuticals [ 12 ], as well in the reduction of environmental CO 2 [ 13 ] and in the polymerization of propylene into
polypropylene [ 14 ]. Despite the relevance of the direct
Abstract Hydroboration and subsequent use of boron
compounds in novel organic synthesis have been fl ourishing in recent years largely due to its amiability in producing asymmetric stereo- and regioselective products. Direct
products of diene hydroboration, however, have received
little attention, with most substrates being assumed to produce the anti-Markovnikov product expected from textbook
organic chemistry understanding. Previous experimental
studies have observed the presence of a plethora of hydroboration products, and a signifi cant progress has been
made in assigning species to experimental data—though
often with contradicting results. This study has used a
computational approach employing quantum chemical
calculations to determine atomic charges of cyclic and
acyclic dienes and correlate these with calculated activation energy barriers in order to predict the regio- and stereoselective outcome of hydroboration reactions. Results
indicated a strong correlation between the most polarized
atomic charges of double-bonded carbons and the lowest
energy transition states as expected. Intriguingly, we identifi ed 1,3-cyclohexadiene as the main example that does
Published as part of the special collection of articles “Festschrift
in honour of P. R. Surjan”.
Electronic supplementary material The online version of this
article (doi: 10.1007/s00214-015-1768-6 ) contains supplementary
material, which is available to authorized users.
* Edina Rosta
edina.rosta@kcl.ac.uk
1
Department of Chemistry , King’s College London ,
London SE1 1DB , UK
2
Melville Laboratory for Polymer Synthesis, Department
of Chemistry , University of Cambridge , Lensfi eld Road ,
Cambridge CB2 1EW , UK
235
Reprinted from the journal