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The role of aryne distortions, steric effects, and charges in regioselectivities of aryne reactions.

Medina JM, Mackey JL, Garg NK, Houk KN - J. Am. Chem. Soc. (2014)

Bottom Line: This model has also provided new fundamental insight into regioselectivity trends in reactions of unsymmetrical arynes, which in turn has fueled advances in aryne methodology and natural product synthesis.This article describes a systematic experimental and computational study of one particularly important class of arynes, 3-halobenzynes. 3-Halobenzynes are useful synthetic building blocks whose regioselectivities have been explained by several different models over the past few decades.We also demonstrate the synthetic utility of 3-halobenzynes for the efficient synthesis of functionalized heterocycles, using a tandem aryne-trapping/cross-coupling sequence involving 3-chlorobenzyne.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.

ABSTRACT
The distortion/interaction model has been used to explain and predict reactivity in a variety of reactions where more common explanations, such as steric and electronic factors, do not suffice. This model has also provided new fundamental insight into regioselectivity trends in reactions of unsymmetrical arynes, which in turn has fueled advances in aryne methodology and natural product synthesis. This article describes a systematic experimental and computational study of one particularly important class of arynes, 3-halobenzynes. 3-Halobenzynes are useful synthetic building blocks whose regioselectivities have been explained by several different models over the past few decades. Our efforts show that aryne distortion, rather than steric factors or charge distribution, are responsible for the regioselectivities observed in 3-haloaryne trapping experiments. We also demonstrate the synthetic utility of 3-halobenzynes for the efficient synthesis of functionalized heterocycles, using a tandem aryne-trapping/cross-coupling sequence involving 3-chlorobenzyne.

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Benzyneinternal angles and transition state for methyl azide/benzynecycloaddition.
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fig7: Benzyneinternal angles and transition state for methyl azide/benzynecycloaddition.

Mentions: In previousarticles,5 we have shown that the reactantdistortion controls regioselectivites by influencing the distortionenergies for attack at C1 vs C2. Figure 7 showsthe geometry of the transition state for methyl azide attack on benzyne(7). As described earlier, the nucleophilic attackof N1 of the azide occurs at the relatively more linear angle on thebenzyne where the π orbital has more p character. The 131°angle is similar to that in benzyne itself (i.e., 127°). Theweaker interaction is at the carbon with the angle of 121°.


The role of aryne distortions, steric effects, and charges in regioselectivities of aryne reactions.

Medina JM, Mackey JL, Garg NK, Houk KN - J. Am. Chem. Soc. (2014)

Benzyneinternal angles and transition state for methyl azide/benzynecycloaddition.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221504&req=5

fig7: Benzyneinternal angles and transition state for methyl azide/benzynecycloaddition.
Mentions: In previousarticles,5 we have shown that the reactantdistortion controls regioselectivites by influencing the distortionenergies for attack at C1 vs C2. Figure 7 showsthe geometry of the transition state for methyl azide attack on benzyne(7). As described earlier, the nucleophilic attackof N1 of the azide occurs at the relatively more linear angle on thebenzyne where the π orbital has more p character. The 131°angle is similar to that in benzyne itself (i.e., 127°). Theweaker interaction is at the carbon with the angle of 121°.

Bottom Line: This model has also provided new fundamental insight into regioselectivity trends in reactions of unsymmetrical arynes, which in turn has fueled advances in aryne methodology and natural product synthesis.This article describes a systematic experimental and computational study of one particularly important class of arynes, 3-halobenzynes. 3-Halobenzynes are useful synthetic building blocks whose regioselectivities have been explained by several different models over the past few decades.We also demonstrate the synthetic utility of 3-halobenzynes for the efficient synthesis of functionalized heterocycles, using a tandem aryne-trapping/cross-coupling sequence involving 3-chlorobenzyne.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.

ABSTRACT
The distortion/interaction model has been used to explain and predict reactivity in a variety of reactions where more common explanations, such as steric and electronic factors, do not suffice. This model has also provided new fundamental insight into regioselectivity trends in reactions of unsymmetrical arynes, which in turn has fueled advances in aryne methodology and natural product synthesis. This article describes a systematic experimental and computational study of one particularly important class of arynes, 3-halobenzynes. 3-Halobenzynes are useful synthetic building blocks whose regioselectivities have been explained by several different models over the past few decades. Our efforts show that aryne distortion, rather than steric factors or charge distribution, are responsible for the regioselectivities observed in 3-haloaryne trapping experiments. We also demonstrate the synthetic utility of 3-halobenzynes for the efficient synthesis of functionalized heterocycles, using a tandem aryne-trapping/cross-coupling sequence involving 3-chlorobenzyne.

Show MeSH
Related in: MedlinePlus