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. 2013 Apr 16;46(4):979-89.
doi: 10.1021/ar3000794. Epub 2012 Jul 24.

Aromatic interactions as control elements in stereoselective organic reactions

Elizabeth H Krenske  1 , K N Houk
Affiliations

Aromatic interactions as control elements in stereoselective organic reactions

Elizabeth H Krenske et al. Acc Chem Res. .

Abstract

This Account describes how attractive interactions of aromatic rings with other groups can influence and control the stereoselectivity of many reactions. Recent developments in theory have improved the accuracy in the modeling of aromatic interactions. Quantum mechanical modeling can now provide insights into the roles of these interactions at a level of detail not previously accessible, both for ground-state species and for transition states of chemical reactions. In this Account, we show how transition-state modeling led to the discovery of the influence of aryl groups on the stereoselectivities of several types of organic reactions, including asymmetric dihydroxylations, transfer hydrogenations, hetero-Diels-Alder reactions, acyl transfers, and Claisen rearrangements. Our recent studies have also led to a novel mechanistic picture for two classes of (4 + 3) cycloadditions, both of which involve reactions of furans with oxyallyl intermediates. The first class of cycloadditions, developed by Hsung, features neutral oxyallyl intermediates that contain a chiral oxazolidinone auxiliary. Originally, it was thought that these cycloadditions relied on differential steric crowding of the two faces of a planar intermediate. Computations reveal a different picture and show that cycloaddition with furan takes place preferentially through the more crowded transition state: the furan adds on the same side as the Ph substituent of the oxazolidinone. The crowded transition state is stabilized by a CH-π interaction between furan and Ph worth approximately 2 kcal/mol. Attractive interactions with aromatic rings also control the stereoselectivity in a second class of (4+3) cycloadditions involving chiral alkoxy siloxyallyl cations. Alkoxy groups derived from chiral α-methylbenzyl alcohols favor crowded transition states, where a stabilizing CH-π interaction is present between the furan and the Ar group. The cationic cycloadditions are stepwise, while the Hsung cycloadditions are concerted. Our results suggest that this form of CH- π-directed stereocontrol is quite general and likely controls the stereoselectivities of other addition reactions in which one face of a planar intermediate bears a pendant aromatic substituent.

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Figures

Figure 1
Figure 1
Transition states for the (4+3) cycloaddition of Hsung’s oxyallyl 13 with furan (B3LYP/6-31G(d), distances in Å, ΔH‡ and ΔG‡ in kcal/mol).
Figure 2
Figure 2
Relative energies of TSC and TSD, computed with different functionals. B3LYP/6-31G(d) geometries were used, and single-point calculations employed the 6-31G(d) basis set except for the points labeled “a”, which employed the 6-311+G(d,p) basis. ΔE‡rel in kcal/mol.
Figure 3
Figure 3
Experimental and calculated stereoselectivities for different oxazolidinone auxiliaries (B3LYP/6-31G(d), kcal/mol). Note: the reversed stereochemical designations for the products from 17 arise from the opposite configuration at C-4 of the oxazolidinone.
Figure 4
Figure 4
Top views of the transition states analogous to TSD for 2-Me, 2-CN, and 2-CO2Me substituted furans (B3LYP/6-31G(d)+LANL2DZ, distances in Å).
Figure 5
Figure 5
Transition structures for (4+3) cycloadditions of Hoffmann’s oxyallyl cation 21 (Ar = Ph) with furan (B3LYP/6-31G(d), distances in Å, ΔH‡ in kcal/mol). The TES group was modeled by TMS.
Scheme 1
Scheme 1
Sharpless asymmetric dihydroxylation of styrene, catalyzed by (DHQD)2PYDZ.,
Scheme 2
Scheme 2
Ruthenium-catalyzed asymmetric transfer hydrogenation of ketones.–
Scheme 3
Scheme 3
Hetero-Diels–Alder reactions of o-xylylenes with benzaldehyde.,
Scheme 4
Scheme 4
Asymmetric hetero-Diels–Alder reactions of Rawal’s diene with aldehydes, catalyzed by a TADDOL derivative.,
Scheme 5
Scheme 5
Enantioselective acyl transfer catalyzed by DHIPs.,
Scheme 6
Scheme 6
Diastereoselective Diels–Alder reactions of anthracene with aryl-substituted maleic anhydride derivatives.
Scheme 7
Scheme 7
Enantioselective Claisen rearrangements catalyzed by chiral guanidinium salts.
Scheme 8
Scheme 8
A strained hydrocarbon stabilized by dispersion interactions.
Scheme 9
Scheme 9
Hsung’s (4+3) Cycloadditions between Oxazolidinone-Substituted Oxyallyls and Furans.
Scheme 10
Scheme 10
(a) Evans’ Oxazolidinone-Directed Diels–Alder Reaction, showing the Proposed Model for Stereoinduction, and (b) Possible Transition Structures for Oxazolidinone-Directed (4+3) Cycloaddition Reactions.
Scheme 11
Scheme 11
Possible Oxyallyl Intermediates and ZnCl2 Complexes.
Scheme 12
Scheme 12
Hoffmann’s Asymmetric (4+3) Cycloaddition, and the Mechanism Originally Proposed to Explain the Stereocontrol.
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References

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    1. Hartree–Fock (HF) theory fails to predict dispersion binding, because it neglects dynamical correlation.

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