Highly Active, Regioselective, and Enantioselective Hydroformylation with Rh Catalysts Ligated by Bis-3,4-diazaphospholanes

Abstract

As with catalytic hydrogenation of alkenes by rhodium complexes, key attributes of rhodium-catalyzed alkene hydroformylation 1 (perfect atom economy, inexpensive reactants, demonstrated performance on industrial scales, readily modified phosphorus ligands) make pursuit of the enantioselective transformation irresistible. Whereas hydrogenation effects net loss of the CdC functional group, hydroformylation results in its transformation to a more versatile functional group, the aldehyde. Although new ligand developments over the last fifteen years have yielded significant progress, the general application of enantioselective hydroformylation lags well behind that of enantioselective hydrogenation. Several factors are responsible: (1) enantioselective hydroformylation is relatively slow, with turnover frequencies commonly in the range of tens to hundreds per hour for terminal alkenes and much slower rates for internal alkenes; (2) effective enantioselective hydroformylation of terminal alkenes requires control of regioselectivity that favors branched isomers; and (3) few of the effective ligands exhibit good activity and selectivity for a range of different substrates, even when one considers only 1-alkenes. We report new chiral bis-3,4-diazaphospholane ligands that constitute unusually active and selective ligands for rhodiumcatalyzed hydroformylation of styrene, allyl cyanide, and vinyl acetate.Recently, we reported the facile synthesis of a wide variety of chiral mono-and bis-3,4-diazaphospholanes 2 that are readily resolved, extended into small libraries, and applied to asymmetric allylic alkylation both in solution 3 and on bead. 4 This work demonstrated that mono-3,4-diazaphospholanes bearing carboxylic acid functionalized substituents in the 2 and 5 positions can be expanded to collections of new ligands using simple coupling chemistry. One-step synthesis of bis-3,4-diazaphospholanes 2 and 3 proceeds with ca. 30% yield upon reaction of the azine 1 with 1,2-diphosphinobenzene in the presence of either succinyl chloride or phthaloyl chloride (Scheme 1). Coupling the carboxylic acid groups of either 2 or 3 with resolved chiral amines followed by chromatographic separation of the resulting diastereomers yields enantiomerically pure bis-3,4-diazaphospholanes 4, 5, 6, and 7.

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

“…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).…”

“…The only ligand that shows higher enantioselectivity for the hydroformylation of vinyl acetate is the recently reported diazaphospholane 4 (96 % ee, b/l = 37:1). [9] A second set of hydroformylation reactions was conducted to compare ligand 12 with ligands 1-4 using mixtures of neat olefins at 80 8C and 1.034 MPa pressure of syngas with substrate/catalyst molar ratios of 30 000:1 and a catalyst concentration of 0.062 mm. At these very low catalyst loadings, the rate of hydroformylation with 12 (an average turnover frequency of 4467 h À1 ) was virtually identical to those of 1 and 2 and only slower than 3 and 4 (see Figure 2).…”

Highly Efficient Rhodium Catalysts for the Asymmetric Hydroformylation of Vinyl and Allyl Ethers using C1‐Symmetrical Diphosphite Ligands

“…[5a] Recently, high regioselectivities and enantioselectivites were reported using bis-phospholane ligands, such as Binapine, [16] TangPhos, [16] Ph-Bpe, [17] Esphos, [18] as well as bis-3,4-diazaphospholane [19] and bis-phosphonite ligands. [20] The first successful report concerning the synthesis of tetrahydrofuran-3-carbaldehyde 12 by Rh-catalysed asymmetric hydroformylation of 2,3-and 2,5-dihydrofurans was published by Nozaki in 1997 (Scheme 2).…”

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.…”

“…This corresponds to the same sense of enantioselection as has been observed in the asymmetric hydroformylation of vinyl acetate using this ligand (styrene also hydroformylates on the same face of the alkene, although the configuration changes due to the priority rules). [12] The N,N-diisopropylamine derivative, 6, was found to be hydroformylated more slowly, but with similar levels of enantioselectivity as the dimethyl analogue (Table 3, runs 7-13). The N,N-diisopropylacrylamide was also found to racemise at a similar rate to the N,N-dimethyl analogue, a drop in ee of 56% to 38% was noted upon standing in CDCl 3 over 24 h. The l-valine methyl ester-derived imine of this substrate was found to be more configurationally stable in chlorinated solvents with no drop in ee upon standing for 24 h in CDCl 3 .…”