Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions

Laurence Hamdan; Khaled Abdel-maksoud; Riya Radia; Janine Boodram; Kwan Y. Man; Iain Mcgregor; Catherine Munteanu; Kishan Muthu; Jannat Poddar; Joanna Roberts; Stephanie Sadler; Nabeela Siddiqi; Sianne Tam; Anna Andreou; Oren A. Scherman; Edina Rosta

doi:10.1007/s00214-015-1768-6

Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions

Laurence Hamdan, Khaled Abdel-maksoud, Riya Radia, Janine Boodram, Kwan Y. Man, Iain Mcgregor, Catherine Munteanu, Kishan Muthu, Jannat Poddar, Joanna Roberts, Stephanie Sadler, Nabeela Siddiqi, Sianne Tam, Anna Andreou, Oren A. Scherman, Edina Rosta

Chemistry

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Abstract

Hydroboration and subsequent use of boron compounds in novel organic synthesis have been flourishing 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 significant 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 identified 1,3-cyclohexadiene as the main example that does 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 specific 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 influenced mainly the stereoselective outcome of the reaction, also affecting the pathways available to proceed through to complete the hydroboration process.

Original language	English
Journal	THEORETICAL CHEMISTRY ACCOUNTS
Volume	135
Issue number	1
Early online date	26 Dec 2015
DOIs	https://doi.org/10.1007/s00214-015-1768-6
Publication status	Published - 1 Jan 2016

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Hamdan, L., Abdel-maksoud, K., Radia, R., Boodram, J., Man, K. Y., Mcgregor, I., Munteanu, C., Muthu, K., Poddar, J., Roberts, J., Sadler, S., Siddiqi, N., Tam, S., Andreou, A., Scherman, O. A., & Rosta, E. (2016). Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions. THEORETICAL CHEMISTRY ACCOUNTS, 135(1). https://doi.org/10.1007/s00214-015-1768-6

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title = "Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions",

abstract = "Hydroboration and subsequent use of boron compounds in novel organic synthesis have been flourishing 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 significant 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 identified 1,3-cyclohexadiene as the main example that does 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 specific 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 influenced mainly the stereoselective outcome of the reaction, also affecting the pathways available to proceed through to complete the hydroboration process.",

author = "Laurence Hamdan and Khaled Abdel-maksoud and Riya Radia and Janine Boodram and Man, {Kwan Y.} and Iain Mcgregor and Catherine Munteanu and Kishan Muthu and Jannat Poddar and Joanna Roberts and Stephanie Sadler and Nabeela Siddiqi and Sianne Tam and Anna Andreou and Scherman, {Oren A.} and Edina Rosta",

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Hamdan, L, Abdel-maksoud, K, Radia, R, Boodram, J, Man, KY, Mcgregor, I, Munteanu, C, Muthu, K, Poddar, J, Roberts, J, Sadler, S, Siddiqi, N, Tam, S, Andreou, A, Scherman, OA & Rosta, E 2016, 'Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions', THEORETICAL CHEMISTRY ACCOUNTS, vol. 135, no. 1. https://doi.org/10.1007/s00214-015-1768-6

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T1 - Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions

AU - Hamdan, Laurence

AU - Abdel-maksoud, Khaled

AU - Radia, Riya

AU - Boodram, Janine

AU - Man, Kwan Y.

AU - Mcgregor, Iain

AU - Munteanu, Catherine

AU - Muthu, Kishan

AU - Poddar, Jannat

AU - Roberts, Joanna

AU - Sadler, Stephanie

AU - Siddiqi, Nabeela

AU - Tam, Sianne

AU - Andreou, Anna

AU - Scherman, Oren A.

AU - Rosta, Edina

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Hydroboration and subsequent use of boron compounds in novel organic synthesis have been flourishing 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 significant 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 identified 1,3-cyclohexadiene as the main example that does 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 specific 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 influenced mainly the stereoselective outcome of the reaction, also affecting the pathways available to proceed through to complete the hydroboration process.

AB - Hydroboration and subsequent use of boron compounds in novel organic synthesis have been flourishing 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 significant 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 identified 1,3-cyclohexadiene as the main example that does 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 specific 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 influenced mainly the stereoselective outcome of the reaction, also affecting the pathways available to proceed through to complete the hydroboration process.

U2 - 10.1007/s00214-015-1768-6

DO - 10.1007/s00214-015-1768-6

M3 - Article

SN - 1432-881X

VL - 135

JO - THEORETICAL CHEMISTRY ACCOUNTS

JF - THEORETICAL CHEMISTRY ACCOUNTS

IS - 1

ER -

Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions

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