Highly Regio‐ and Enantioselective Asymmetric Hydroformylation of Olefins Mediated by 2,5‐Disubstituted Phospholane Ligands

Abstract

Asymmetric hydroformylation (AHF) is a powerful synthetic methodology that allows conversion of olefins into optically active aldehydes in a single step [Eq. (1)].[1] The aldehyde group is one of the most versatile functional groups and can be readily transformed into a variety of high-value-added chiral chemicals, such as amines, imines, alcohols, and acids.[2]Even though AHF offers great promise to the fine-chemical industry, this reaction has not been utilized on a commercial scale because of several remaining technical challenges; among the most important to overcome are a) low reaction rates at low temperatures for reactions in which good selectivities are usually observed, b) difficulties in controlling the regio-and enantioselectivities simultaneously, and c) limited substrate scope for any single ligand. The reaction rates of Rh-catalyzed hydroformylations are commonly slower than those of asymmetric hydrogenations that are conducted near ambient temperature. Commercially viable rates in AHF can be achieved at 80-120 8C (turnover rates of several thousand per hour); however, lower regioand enantioselectivities are usually observed at these high temperatures. Thus, the most desired characteristic of the new generation of AHF ligands should be the ability to produce optically active aldehydes at high temperatures without compromising product selectivity.Only a few chiral ligands have been successfully applied in AHF reactions (Scheme 1). Among the most effective are (2R,4R)-chiraphite (1) [3] and its analogues, [4] which exhibit enantioselectivities of up to 90 % ee for the hydroformylation of styrene at low temperatures; (R,S)-binaphos (2), [5] which shows high enantioselectivities for the hydroformylation of many structurally diverse olefins; (S,S)-kelliphite (3), which is effective for the hydroformylation of allyl cyanide [6] and vinyl acetate; [7] and (S,S)-esphos (5), which displays a high enantioselectivity for the hydroformylation of vinyl acetate. [8] Together with Landis and co-workers, we recently reported [9] the application of diazaphospholane ligands 4 in AHF reactions which showed outstanding hydroformylation rates and very high enantioselectivities for reactions with styrene and allyl cyanide substrates. Diazaphospholane 4 is especially selective for vinyl acetate at 80 8C (96 % ee, b/l = 35). This ligand family is structurally related to 1,2-bis(2,5-dialkylphospholano)benzene (duphos; 6-8), 1,2-bis(2,5-dialkylphospholano)ethane [10] (bpe; 9-11), and especially the recently reported (R,R)-1,2-bis(2,5-diphenylphospholano)ethane ((R,R)-Ph-bpe; 12) Scheme 2).[11] The duphos and bpe ligands [12] have been proven to be exceptional ligands for the asymmetric hydrogenation [13] of dehydroamino acids and mono-and disubstituted itaconates, among numerous other applications, but their use has not been reported for AHF reactions.Herein, we report that 12 is an excellent ligand for the rhodium-catalyzed AHF of styrene, allyl cyanide, and vinyl acetate at high temperatures (80-100 8C). (R,R)-Ph-bpe (12...

Regioselective and Enantioselective Hydroformylation of Dialkylacrylamides

“…The chiral ligands chosen for initial studies on the hydroformylation of dimethylacrylamide were (R,R)-PhBPE, [13] (R,R)-Chiraphite, [7,10] (R,R)-Kelliphite, [7,8] the phosphine-phosphite ligands denoted POP, [14] while later studies used the (S,S,S) or (R,R,S)-Diazaphos-SPE ligand, developed by Landis and co-workers [12] (see Figure 1). The ligand to Rh ratio was 1.25:1, since in many many experiments with a wide variety of alkenes, we have observed that ratios of 1.1-1.5 generally give the best results.…”

P‐Chirogenic Benzo‐Fused Phenoxaphosphane: Synthesis, Resolution and Study of the Stereochemical Properties of the Corresponding Palladium Complexes

“…[1,2] This attention for these P-heterocycles can be ascribed to the incessant search for novel structures, suitable as chiral ligands in asymmetric catalysis, pursued by researchers involved in the field of ligand development. In this regard, chiral phosphacycle-based ligands, which as a consequence of their ring constraints bear unique steric and electronic properties often remarkably different from their acyclic counterparts, are a new intriguing class of enantio-inductors for asymmetric transformations.…”

“…[4a,4b] An increasing variety of chiral phosphacycles of different ring extensions, ranging from four to seven units, have since then been prepared and applied successfully in asymmetric catalysis. [2,3,5,6] Benzo-fused phenoxaphosphanes, a class of conjugated phosphorus-based heterocycles, were initially introduced by Mann and Millar in the late 1950's and since then have found applications mostly in the development of new polymeric materials. [7,8] The potential of these cyclic analogues of triphenylphosphane in catalysis has remained hitherto tion of enantiopure phosphanes 3a,b was assigned unequivocally by means of X-ray crystal structure determination for complex 9a and by combination of NOE( unexpressed as is demonstrated by the very few articles regarding the applications of these compounds.…”

“…[10] In this context, the synthesis of chiral benzo-fused phenoxaphosphane compounds represents the next step due to the high degree of enantio-discrimination chiral phosphacycles can induce in asymmetric metal-catalyzed reactions. [1][2][3][4][5][6] In this work we describe the synthesis and optical resolution of the first benzo-fused phenoxaphosphane 3 in which a hydroxyl moiety, amenable to further functionalization, is attached to the rigid phenoxaphospanyl skeleton. Moreover, given the influence exerted by the ligand/metal stereoelectronic interactions in controlling a catalytic process and in view of the employment of chiral phenoxaphosphane-based ligands in asymmetric catalysis we carried out an in-depth investigation of the stereochemical properties of 3 and derivatives thereof.…”

New C2‐Symmetric Diphosphite Ligands Derived from Carbohydrates: Effect of the Remote Stereocenters on Asymmetric Catalysis

“…Other remarkable C 2 -symmetric ligands, derived from mannitol, successfully applied in asymmetric hydrogenation are the 2,5-disubstitued phospholane ligands (Duphos derivatives) 7 and 8 [14] and the related DIOP, [15] analogue. These 2,5-disubstitued phospholane ligands have recently been identified as excellent ligands for the rhodium-catalysed asymmetric hydroformylation providing high turnover rates and enantioselectivities for styrene, allyl cyanide, vinyl acetate [16] and [2.2.1]-bicyclic olefins. [17] We have recently reported the synthesis of C 2 -symmetric diphosphinite ligands 9 and 10 derived from carbohydrates with a furanoid backbone.…”