Asymmetric Rh-Catalyzed Intermolecular Hydroacylation of 1,5-Hexadiene with Salicylaldehyde

Abstract

Rh-catalyzed intramolecular [1][2][3][4][5][6][7] and intermolecular hydroacylations [8][9][10][11][12][13][14][15][16][17][18][19] have recently been the focus of synthetic organic and organometallic chemists. Although Rh-catalyzed asymmetric intramolecular hydroacylation (asymmetric cyclization) has been extensively studied by us, [20][21][22][23][24] and other groups, [25][26][27][28] Rh-catalyzed asymmetric intermolecular hydroacylation has attracted only limited attention, 29-31) except for asymmetric hydroformylation. 32,33) This may be because Rh-catalyzed intermolecular hydroacylation did not proceed under mild reaction conditions, but required vigorous reaction conditions. Recently, we have found that Rh-catalyzed intermolecular hydroacylations proceed under mild reaction conditions based on the "double chelation" of aldehyde and diene (Eq. 1).34-37) Here we report enantioselective Rh-catalyzed intermolecular hydroacylation between salicylaldehyde (1) and 1,5-hexadiene (2).(1)The hydroacylation between salicylaldehyde (1) and 1,5-hexadiene (2, 6 eq) using RhCl(PPh 3 ) 3 (0.20 eq) at room temperature afforded a mixture of iso-hydroacylated product 3 and normal-hydroacylated product 3 in the ratio of 4 to 1 in quantitative yield (Eq. 1). The iso-hydroacylated product 3 has a chiral carbon at the a-position. Thus, we envisaged that the asymmetric induction from prochiral 1,5-hexadiene would be possible, if Rh-complex with chiral phosphine ligand were used instead of achiral RhCl(PPh 3 ) 3 .First, we examined the hydroacylation between salicylaldehyde (1) and 1,5-hexadiene (2) using Rh[(R)-BINAP]Cl (0.40 eq) at room temperature. Fortunately, the reaction afforded the mixture of iso-3 and normal-3 in the ratio of 3 to 1, and the specific rotation [a] D of the mixture showed ϩ9.6. This result means that the iso-product is not racemic but optically active, even though the chemical yield was merely 4% (entry 1 in Table 1). This result prompted us to further improve the chemical yield of the product and increase its specific rotation. We increased the amount of Rh-catalyst to 1.0 eq, but the yield of products was not improved. Several additives, such as bases, silver salts, and Lewis acids, were then examined, as shown in Table 1. We thought that the addition of base would deprotonate phenolic protons of salicylaldehyde and promote hydroacylation. In contrast, the addition of silver salt would change the property of Rh-complex to a cationic species to accelerate the reaction. Unfortunately, the addition of bases, such as K 2 CO 3 , KOAc, and NaOAc, did not improve the yield (entries 3-5), and the addition of silver salts, such as AgClO 4 and CF 3 CO 2 Ag, improved the yield of products but their specific rotations were zero, meaning that the products were racemic (entries 6-8). Finally, it was found that the addition of Lewis acid improved the yield of products (entries 9-12); in particular, the addition of Zn(OTf) 2 (0.20 eq) improved the yield of product and its specific rotation showed Ϫ26°(entry 11). However...

Rh(I)-Catalyzed Intermolecular Hydroacylation: Enantioselective Cross-Coupling of Aldehydes and Ketoamides

“…have been found to be beneficial in a study on intermolecular alkene hydroacylation, although their role is unclear. 37 The mechanism proceeds with insertion to generate acyl-Rh(III)-alkoxide V , followed by reductive elimination to furnish the product and turnover the Rh(I) catalyst. It is possible for the reaction to occur through bimetallic intermediates following oxidative addition; however, reactive intermediates were not observed spectroscopically.…”

Rhodium‐Catalyzed Branched‐Selective Alkyne Hydroacylation: A Ligand‐Controlled Regioselectivity Switch

“…have both reported branched‐selective Ru‐catalyzed diene hydroacylations; Suemune et al 2a. 4d and Dong et al 4g. have exploited chelating alkenes to achieve branched‐selectivity, and Krische et al.…”

Rhodium-catalyzed enantioselective intermolecular hydroacylation reactions

“…In this second system, 1,5-hexadiene substrates were employed to provide branched-selective hydroacylation products via a double-chelation model in which both the aldehyde and the diene act as chelating components (Scheme 5) [13]. Good enantioselectivities (up to 78 % ee) were obtained for reactions employing (S)-BINAP (6) as the chiral ligand; however, the reactions were not completely regioselective, and linear, achiral products were also isolated.…”