Enantioselective Hydrogenation of α-Aryloxy and α-Alkoxy α,β-Unsaturated Carboxylic Acids Catalyzed by Chiral Spiro Iridium/Phosphino-Oxazoline Complexes

Abstract

The iridium-catalyzed highly enantioselective hydrogenation of alpha-aryloxy and alpha-alkoxy-substituted alpha,beta-unsaturated carboxylic acids was developed. By using chiral spiro phosphino-oxazoline ligands, the hydrogenation proceeded smoothly to produce various alpha-aryloxy- and alpha-alkoxy-substituted carboxylic acids with extremely high enantioselectivities (ee up to 99.8%) and reactivities (TON up to 10,000) under mild conditions. The hydrogenation of alpha-benzyloxy-substituted alpha,beta-unsaturated acids provided an efficient alternative for the synthesis of chiral alpha-hydroxy acids after an easy deprotection. A mechanism involving a catalytic cycle between Ir(I) and Ir(III) was proposed on the basis of the coordination model of the unsaturated acids with the iridium metal center. The rationality of the catalytic cycle, with an olefin dihydride complex as the key intermediate, was supported by the deuterium-labeling studies. The X-ray diffraction analysis of the single crystal of catalyst revealed that the rigid and sterically hindered chiral environment created by the spiro phosphino-oxazoline ligands is the essential factor that permits the catalyst to obtain excellent chiral discrimination. A chiral induction model was suggested on the basis of the catalyst structure and the product configuration.

DFT Methods to Study the Reaction Mechanism of Iridium‐Catalyzed Hydrogenation of Olefins: Which Functional Should be Chosen?

“…[12][13][14] Initiated by this groundbreaking discovery, hundreds of chiral iridium-based catalystsh ave been developed and tested for variousalkene hydrogenations. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In this regard, theoretical computation and modeling could potentially contribute to solving this conundrum, due to the lack of much relevant experimentald ata. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In this regard, theoretical computation and modeling could potentially contribute to solving this conundrum, due to the lack of much relevant experimentald ata.…”

“…By employing Ir/P,Ntype structuresa nd ethylene as the model system, four previously proposed mechanisms of iridium-catalyzed olefin hydrogenationa re illustrated in Figure 2. [23][24][25][26][27][28] In these two mechanisms, labeled as I/III-MI-Solv and I/III-MI,t he hydrogenating iridium(III) dihydride species is first formed through the oxidative addition (OA) of the iridium(I) dihydrogen complex. [23][24][25][26][27][28] In these two mechanisms, labeled as I/III-MI-Solv and I/III-MI,t he hydrogenating iridium(III) dihydride species is first formed through the oxidative addition (OA) of the iridium(I) dihydrogen complex.…”

“…[1][2][3][4][5][6][7][8][9][10] However,i nc ontrastt or elatedr uthenium-based and rhodium-based catalytic hydrogenation, [15][16][17][18][19][20][21][22] the mechanism of the iridium-catalyzed hydrogenation is still not fully clarified. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In this regard, theoretical computation and modeling could potentially contribute to solving this conundrum, due to the lack of much relevant experimentald ata. By employing Ir/P,Ntype structuresa nd ethylene as the model system, four previously proposed mechanisms of iridium-catalyzed olefin hydrogenationa re illustrated in Figure 2.…”

Comparison of Asymmetric Hydrogenations of Unsaturated Carboxylic Acids and Esters

“…28 Several α-alkoxy-derivatives were hydrogenated with high enantiomeric excesses, as illustrated in Figure 8.…”

Asymmetric Hydrogenation

“…Therefore, not only unfuctionalized alkenes but also alkenes with functional groups connected to their C=C double bonds have been hydrogenated with high to excellent enantioselectivity. Figure 6 shows examples of the [61], furan rings [62], -dehydroamino acid derivatives [63], ,β-unsaturated ketones [64],,β-unsaturated carboxylic acid esters [61], -alkoxy ,β-unsaturated acids [65], vinylphosphine oxides [66], enol phosphinates [67], vinyl boronates [68], and enamines [69,70]. Notably, substituted furans, vinyl boronates, and even enamines are hydrogenated with full conversion in high to excellent enantioselectivity.…”