Isomerization of Olefins Triggered by Rhodium-Catalyzed C–H Bond Activation: Control of Endocyclic β-Hydrogen Elimination

Five-membered metallacycles are typically reluctant to undergo endocyclic β-hydrogen elimination. The rhodium-catalyzed isomerization of 4-pentenals into 3-pentenals occurs through this elementary step and cleavage of two C–H bonds, as supported by deuterium-labeling studies. The reaction proceeds without decarbonylation, leads to trans olefins exclusively, and tolerates other olefins normally prone to isomerization. Endocyclic β-hydrogen elimination can also be controlled in an enantiodivergent reaction on a racemic mixture.

Five-membered metallacycles are important intermediates of numerous catalytic processes,b oth in academic laboratories and in large-scale industrial chemistry. [1] As shown in experimental [2] and theoretical [3] studies,g eometric constraints make these intermediates reluctant to undergo endocyclic b-hydrogen (b-H) elimination, especially in the case of square-planar complexes.H owever,a nd although thorough experimental studies are still lacking, theoretical studies suggest that five-membered metallacycles that are not square-planar could undergo b-H elimination more easily. [4] Fore xample,r ecent calculations indicate that the rhodiumcatalyzed decarbonylation of 4-pentenals could occur by reversible endocyclic b-H elimination of intermediate A (R = H) (Figure 1). [5] Importantly,s ubstrate decarbonylation is anotorious problem during the hydroacylation of 4-pentenals, especially in the case of a,a-disubstituted aldehydes (R ¼ 6 H). [6][7][8][9] In contrast, we have found that the rhodium-catalyzed isomerization of 4-pentenal 1 (R = Ph) into 3-pentenal 2 occurs without decarbonylation in 86 %yield and in ahighly stereoselective fashion. Them ost efficient catalyst was prepared with ligand L1, [10] whereas those prepared with L2-L5 led to incomplete conversion and decarbonylation. Hence,weassumed this isomerization to be triggered by C À H bond activation (a), and the catalytic cycle would be completed by migratory insertion of the terminal olefin into the rhodium-hydrogen bond thus engendered (b), followed by endocyclic b-H elimination of A (R = Ph) (c), and final reductive elimination (d).
Herein, we report at horough study of the reaction depicted in Figure 1, including deuterium-labeling experiments that support the postulated mechanism and the endocyclic b-H elimination of rhodacyclopentanone A. Moreover,w ea lso show that the isomerization is chemoselective for olefins that enable the formation of A,a nd that olefins located elsewhere on the substrate remain intact under the reaction conditions,e ven in the challenging case of sensitive olefins normally prone to facile isomerization in the presence of transition-metal catalysts, [11] including rhodium catalysts. [12] Finally,w ed escribe how the endocyclic b-H elimination of rhodacyclopentanones can be prevented, whereby each enantiomer of the racemic 4-pentenal undergoes ad istinct and enantioselective rearrangement when treated with an enantiopure catalyst.
We found that the rhodium-catalyzed isomerization of deuterated substrates 3 and 4 into compounds 5 and 6, respectively,occurred smoothly with complete transfer of the deuterium atom at the positions indicated in Scheme 1. Tr ansient intermediate 3-int was observed in the isomer- ization of 3 into 5,i ndicating that step (b) in Figure 1i s reversible. [13] No intermolecular transfer of the deuterium atom was observed when 3 and 7 were treated with the rhodium catalyst. Instead, 5 and 8 were obtained in 75 %and 93 %yield, respectively.T he results of these experiments are in good agreement with the intramolecular addition of an acylhydridorhodium intermediate and the endocyclic b-H elimination envisioned in Figure 1. In contrast to many precedents,n either the reversible intermolecular addition of am etal-hydride species [14] nor allylic CÀHa ctivation [15] can account for the olefin isomerization examined herein.
We then explored the generality of the isomerization of 4pentenals into 3-pentenals with substrates 9a-9o and observed in all cases the stereoselective formation of 10 a-10 o as trans isomer only (Scheme 2). This exquisite transselectivity could be explained by the fact that the hydrogen atom highlighted by agray disc in A (Figure 1) is the only one in this conformer of the five-membered metallacycle which is correctly positioned to develop an agostic interaction with the metal prior to b-H elimination. [5,16] Hence,p lacing the cis isomer of 10 a under the reaction conditions led to only limited isomerization into its trans isomer (Z/E = 4.7:1). Monosubstituted 9i could be converted into 10 i,a lbeit with decomposition owing to the instability of both 9i and 10 i, even in the absence of catalyst. [17] Remarkably,other olefins, such as the remote terminal olefin in 10 k,a na llylbenzene (10 l), an allylic ether (10 m), an allylic amide (10 n), and a1,4enyne (10 o), remained unaffected by the active rhodium catalyst, although they are all susceptible to undergo metalcatalyzed isomerization. [11,12] The1 ,1-disubstituted olefin in 11 does not undergo isomerization but sluggish intramolecular hydroacylation, and 12 was isolated in low yield besides the recovered starting material [Eq. (1)].T he isomerization of 1,2-bisubstituted olefin 13 into 14 is reversible and placing either 13 or 14 under the reaction condition leads to the same 13/14 ratio [Eq. (2)],a lthough the reaction of 14 led to traces of decarbonylated olefins as well. In view of the inertness of 11 and the notoriously low yields of formation of a,adisubstituted cyclopentanones in hydroacylation reactions, [7,8] we were surprised to observe that the treatment of 15 with the active rhodium catalyst led to the isolation of 17 in 97 %yield as as ingle diastereomer,a sc onfirmed by NOESY (Scheme 3). Importantly,c ompound 16 could be isolated as transient intermediate in the formation of racemic 17 at room temperature:at50% conversion, 16 accounts for 45 %ofthe mass balance.T he strikingly different reactivity of 11 and 16 suggests that the 1,2-disubsituted olefin of 16 facilitates the observed intramolecular hydroacylation. This tandem reaction could also be observed with other substrates (see the Supporting Information).  Considering the rare examples of simple kinetic resolution in the rhodium-catalyzed hydroacylation of 4-pentenals into cyclopentanones, [7b,c,18] and parallel kinetic resolutiono f 4-alkynals, [19] we were curious to evaluate the effect of an enantiopure catalyst on the reaction of (AE)-18.Using (R)-L1 as ligand, we obtained (R)-19 besides am ixture of (S,S)-20 and (S)-21 ( Figure 2). Reduction of the latter compounds enabled the separation of (R)-22 and the determination of its enantiomeric purity,which is assumed to be the same for (S)-21.T he absolute stereochemistry of (R)-19 was assigned by comparison with similar compounds, [20] and X-ray crystallography of ester (S)-23 confirmed the configuration of (S)-21. [21] Thea bsolute stereochemistry and enantiomeric purity of (S,S)-20 were deduced by considering the mass balance and the enantiomeric ratios of the other products obtained in this reaction after full conversion, using the mathematical treatment proposed by Horeau. [22] Significantly,w eo bserved that 19 is formed more quickly than 20 and 21:at10% conversion, 19 accounts for more than 8%of the mass balance whereas 20 and 21 account less than 2% together.A ccordingly,t he behavior of (AE)-18 in the presence of an enantiopure catalyst is best described as adivergent reaction on aracemic mixture (RRM), [23] whereby each enantiomer follows predominantly adistinct reaction pathway,(R)-18 leading to (R)-19,and (S)- In conclusion, we have identified several factors which control the behavior of ak ey five-membered metallacycle intermediate in the isomerization of 4-pentenals into 3pentenals in terms of chemo-and stereoselectivity.Endocyclic b-H elimination of this intermediate enables the stereoselective formation of a trans olefin with exquisite control. Alternatively,t his elementary step can be prevented by ac oordinating group,i nw hich case it is possible to observe as pecific reaction for each enantiomer of the racemic 4pentenal in the presence of an enantiopure catalyst.

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