Highly Selective Asymmetric Rh-Catalyzed Hydroformylation of Heterocyclic Olefins

Abstract

A small family of new chiral hybrid, diphosphorus ligands, consisting of phosphine-phosphoramidites L1 and L2 and phosphine-phosphonites L3a−c, was synthesized for the application in Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins. High-pressure (HP)-NMR and HP-IR spectroscopy under 5−10 bar of syngas has been employed to characterize the corresponding catalyst resting state with each ligand. Indole-based ligands L1 and L2 led to selective ea coordination, while the xanthene derived system L3c gave predominant ee coordination. Application of the small bite-angle ligands L1 and L2 in the highly selective asymmetric hydroformylation (AHF) of the challenging substrate 2,3-dihydrofuran (1) yielded the 2-carbaldehyde (3) as the major regioisomer in up to 68% yield (with ligand L2) along with good ee's of up to 62%. This is the first example in which the asymmetric hydroformylation of 1 is both regio-and enantioselective for isomer 3. Interestingly, use of ligand L3c in the same reaction completely changed the regioselectivity to 3-carbaldehyde (4) with a remarkably high enantioselectivity of 91%. Ligand L3c also performs very well in the Rh-catalyzed asymmetric hydroformylation of other heterocyclic olefins. Highly enantioselective conversion of the notoriously difficult substrate 2,5-dihydrofuran (2) is achieved using the same catalyst, with up to 91% ee, concomitant with complete regioselectivity to the 3-carbaldehyde product (4) under mild reaction conditions. Interestingly, the Rh-catalyst derived from L3c is thus able to produce both enantiomers of 3-carbaldehyde 4, simply by changing the substrate from 1 to 2. Furthermore, 85% ee was obtained in the hydroformylation of N-acetyl-3-pyrroline (5) with exceptionally high regioselectivities for 3-carbaldehyde 8Ac (>99%). Similarly, an ee of 86% for derivative 8Boc was accomplished using the same catalyst system in the AHF of N-(tert-butoxycarbonyl)-3-pyrroline (6). These results represent the highest ee's reported to date in the AHF of dihydrofurans (1, 2) and 3-pyrrolines (5, 6).

Bismuthanes as Hemilabile Donors in an O2‐Activating Palladium(0) Complex

“…The synthesis of Xan(PPh 2 )(BiPh 2 )s tarted with the introduction of the phosphanef ragment to the xanthene backbonea ccording to am odified literature procedure. [9] For this, XanBr 2 was lithiated with one equivalent of phenyllithium and then treated with one equivalent of Ph 2 PCl in tetrahydrofuran. The bismuthane unit wast hen introduced through as econd lithiation and as ubsequent reaction with Ph 2 BiCl (Scheme1).…”

Isomerizing Hydroformylation of Cashew Nut Shell Liquid

“…The corresponding proton NMR spectrum of this solution displayed a broad doublet centered at −10.35 ppm with a J P‐H / J Rh‐H coupling constant of <3.5 Hz. A doublet in the 31 P NMR spectrum and a fairly small J P‐H is a characteristic of a predominantly equatorial–equatorial (ee) coordination mode of the two phosphorus donors (Scheme , species C2 ) . Similar results were obtained in the presence of substrate (Figures S34–35 in the Supporting Information).…”

Isomerisation versus carbonylative pathways in the hydroxy-carbonylation, methoxy-carbonylation, and amino-carbonylation of N-tosyl-3-pyrroline

“…6 As part of a programme aiming to increase scope in this class of reaction, we have studied carbonylation of N-tosyl-3-pyrroline. Interest in the catalytic asymmetric synthesis of β-Proline derivatives is exemplified by a recent study reporting enantioselective hydroformylation of N-Boc-2-pyrroline, 7 while we recently reported the related transfer hydroformylation of N-tosyl pyrroline with around 70-75% e.e. 8 To access β-Proline requires oxidation and deprotection.…”