(47c) Tuning Solid Catalysts to Control Regioselectivity in Cross-Aldol Condensations with Unsymmetrical Ketones

Authors: 
Ponnuru, K., University of Massachusetts
Jentoft, F. C., University of Massachusetts
Cho, H. J., University of Massachusetts
Fan, W., University of Massachusetts
Manayil, J., Aston University
Wilson, K., RMIT University
Aldol condensation is an important C-C bond formation reaction in chemical synthesis that finds versatile applications in bulk and fine chemical industries and has potential for valorizing carbonyl compounds in biomass-derived pyrolysis oils to longer carbon chain compounds with lower oxygen content. Another key feature of aldol condensation is regioselectivity that can be catalytically controlled to preferentially obtain branched or straight carbon chains that are crucial in the synthesis of a variety of aroma chemicals.

Regioselective control has been successfully demonstrated in homogeneous catalysis using organocatalysts,[1-4] but they are unsuitable for large-scale processing and pose problems with catalyst separation and recycling.[5] Investigations focusing on mechanistic detail of surface-catalyzed aldol reactions are lacking and the few reports that detail controlling the regioselectivity with soluble or solid inorganic catalysts[6, 7] do not demarcate the addition and dehydration steps, which is essential to ascertain the course of the reaction. The objective of this investigation is thus to identify the factors that govern regioselectivity in heterogeneously catalyzed cross aldol reactions and to delineate the two aldol reaction steps.

Several families of catalysts with characteristic acid or base sites and with different pore architectures were investigated including (i) propyl sulfonic-acid (PrSO3H) functionalized SBA-15 with various acid loadings and with or without hydrophobization by octyl groups (Oc), (ii) isomorphously substituted BEA zeotypes with Sn, Ti, Zr and Hf, (iii) primary (-NH2) and secondary (-NHR) amine-functionalized SBA-15 and (iv) Cation-exchanged BEA zeolites. Molecular catalysts with appropriate functional groups (-SO3H, -NH2, -NHR, andCH3O-) served as benchmarks. The aldol condensation of benzaldehyde and 2-butanone provided opportunity for regioselectivity through preferential formation of branched (reaction at -CH2- of butanone) or linear (reaction at -CH3) addition and condensation products.

Product distributions analyzed at different conversions revealed how kinetics and equilibria of the addition and dehydration steps govern regioselectivity. Solid acid (-SO3H) catalysts favored the branched condensation product like their soluble counterpart. This result is consistent with fast dehydration catalyzed by the strong acid and consequently, regioselectivity is determined by the preferred formation of the branched aldol. In the absence of strong acid sites (BEA zeotypes), the linear condensation product predominated since dehydration of the respective aldol is facile, consistent with earlier observations in the literature.[8] Solid amine catalysts preferentially formed linear condensation products as a consequence of enamine intermediate formation at the less substituted methyl carbon. These results demonstrate that regioselectivity of aldol reactions can be controlled by tuning the nature, density and environment of the active surface site. Purely inorganic catalysts have the additional advantage of being regenerable by calcination.

References:

[1] W. Notz, B. List, J. Am. Chem. Soc. 122 (2000) 7386–7387.

[2] S. Samanta, J. Liu, R. Dodda, C.-G. Zhao, Org. Lett. 7 (2005) 5321–5323.

[3] S. Luo, H. Xu, J. Li, L. Zhang, J.-P. Cheng, J. Am. Chem. Soc. 129 (2007) 3074–3075.

[4] S.S. Chimni, S. Singh, D. Mahajan, Tetrahedron: Asymmetry 19 (2008) 2276–2284.

[5] M. Gruttadauria, F. Giacalone, R. Noto, Chem. Soc. Rev. 37 (2008) 1666–1688.

[6] G. Liang, A. Wang, X. Zhao, N. Lei, T. Zhang, Green Chem. 18 (2016) 3430–3438.

[7] L. Zhao, N. Elechi, R. Qian, T.B. Singh, A.S. Amarasekara, H.J. Fan, J. Phys. Chem.A 121 (2017) 1985–1992.

[8] M. Stiles, D. Wolf, G.V. Hudson, J. Am. Chem. Soc. 81 (1959) 628–632.