Keulemans’ rules

Due to Keulemans rule, the addition of the formyl group is favored at the lower-substituted carbon atom. In the example of a terminal double bond, the linear regio-isomer is preferred in comparison to the iso-isomer. In several applications, the linear products are more valuable than the branched products, so there are some efforts to influence the tr.iso ratio [9]. 

It has been stated that a formyl group formed during the hydrofoimylation reaction of unfunctionalized olefins is unlikely to be attached to a quaternary carbon atom (the Keulemans rule). An example of this general rule is the oxo reaction with 2,3-dimethyl-2-butene, where 3,4-dimethylpentanal is formed exclusively. For both rhodium and cobalt catalysts, isomerization of the substrate is followed by hydrofoimylation (Scheme 1) [47, 48]. 

The reaction of branched olefins requires more severe reaction conditions or, alternatively, a more reactive catalyst. Principally, hydroformylation of triple substituted, sp -configurated C atoms is unfavorable ( Keulemans rule ) [3]. Migration of the double bond may change the structure of the original substrate. 

The problem of highly branched regioselectivity required for AHF of terminal olefins can be alternatively overcome by taking benefit from Keulemans rule (E) [2]. According to this rule, with 1,1-disubstituted alkenes the C-C bond formation... 

Wang and Buchwald [2, 58] generated chiral P-formyl esters from a-alkyl acrylates by taking benefit from Keulemans rule. Remarkably, all privileged ligands developed for AHF induced poor results. The optimal catalyst identified was based on the P-chiral diphosphine (R,R)-BenzP (Scheme 4.83). In order to achieve full conversion, a fivefold excess of H2 in comparison to CO was necessary. These structures can be found in inhibitory agents owned by Pfizer and Roche, respectively. 

BASF claimed the hydroformylation of numerous a-branched styrenes (Scheme 6.60) [164]. For example, in a 3 kg scale, 2-(4-isopropylphenyl)-prop-l-ene was reacted in the presence of an unmodified rhodium catalyst to give, in accordance with Keulemans rule, exclusively the terminal aldehydes. 

Thus, the rule of Keulemans (49), that a-quaternary carbon formyl compounds are not formed, was followed. The olefin isomerized to allow formyl attachment to a primary carbon atom. Addition of phosphine, which decreases isomerization, resulted in no reaction. 

One of the most interesting observations is that the a-isomer (9) contains a quaternary carbon atom attached to the formyl group, which is a violation of the rule of Keulemans (49). It must be that electronic effects are dominant for this type of substrate, particularly when the effects of phosphine-modified rhodium systems are considered (vide infra). 

Substitution on the double-bond carbon a to the oxygen increased the difficulty of the reaction, and formyl attachment occurred exclusively on the /3-carbon [Eq. (42)]. Thus, these substituted olefins also followed the rule of Keulemans (49). 

Gorter, S. Rutten-Keulemans, E. Krever, M. Romers, C. Cmickshank, D. W. J. [18]-annulene, CjgHjg, structure, disorder and Hueckel s 4n 4- 2 rule, Acta Crys-tallogr. B1995,51,1036-1045. 

This result can be easily explained by the assumption of Abutene as intermediate and its hydroformylatiun according to Keuleman s rule 60]. 

The technical application of the hydroformylation reaction has developed rapidly due to the industrial importance of its products. Many data were obtained during this development work, which allowed H. J. Nien-burg et aL [236] and A. J. M. Keulemans, A. Kwantes and Th. van Bavel [25] to lay down certain empirical rules for the oxo reaction. For quite some time these rules were the basis for the understanding of the product distribution in the hydroformylation reactions. There was no systematic investigation of the reaction mechanism of this process in the early years. Unsatisfactory analytical results were responsible for many misinterpretations. It was assumed that the hydroformylation proceeds through heterogeneous catalysis, an assumption which is supported by some authors even in the sixties [26, 27] (as to these papers see the critical discussion in the paper of V. Macho et aL [28]). 

In this case, contrary to the rules of Keulemans, a compound containing a quarternary carbon atom is made in high yield. 

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