Highly enantioselective hydroformylation of aryl alkenes with diazaphospholane ligands

Asymmetric, rhodium-catalyzed hydroformylation of terminal and internal aryl alkenes with diazaphospholane ligands is reported. Under partially optimized reaction conditions, high enantioselectivity (>90% ee) and regioselectivities (up to 65:1 alpha:beta) are obtained for most substrates. For terminal alkenes, both enantioselectivity and regioselectivity are proportional to the carbon monoxide partial pressure, but independent of hydrogen pressure. Hydroformylation of para-substituted styrene derivatives gives the highest regioselectivity for substrates bearing electron-withdrawing substituents. A Hammett analysis produces a positive linear correlation for regioselectivity.     

Synthesis and Application of Tetraphosphane Ligands in Rhodium‐Catalyzed Hydroformylation of Terminal Olefins: High Regioselectivity at High Temperature

A new class of substituted tetraphosphane ligands has been developed and applied in the rhodium‐catalyzed regioselective hydroformylation of terminal olefins. The high regioselectivity (linear selectivity is above 97 % for 1‐octene and 1‐hexene) at high temperature (140 °C) shown by these tetraphosphane ligands is remarkable considering the low regioselectivity commonly observed under similar reaction conditions when other bisphosphane analogues are used. The steric and electronic effects of substituents on the diarylphosphane moiety have also been examined.     

Ferrocene-based bidentate phosphonite ligands for rhodium(I)-catalyzed enantioselective hydroformylation

A new class of chiral modular bidentate phosphonite ligands has been synthesized in good overall yields by using cheap trans-1,2-diaminocyclohexane and ferrocene as starting materials, and applied in the Rh(I)-catalyzed asymmetric hydroformylation of vinyl acetate and styrene to afford the corresponding optically active aldehydes with good regioselectivity (up to 16.9 b/l ratio) and moderate to good enantioselectivity (up to 83% ee). The substituents on the backbone of the ligands are found to exhibit a remarkable effect on both the regio- and enantioselectivity of the catalysis.     

Unraveling the origin of regioselectivity in rhodium diphosphine catalyzed hydroformylation. A DFT QM/MM study

The origin of regioselectivity in rhodium diphosphine catalyzed hydroformilation was investigated by means of hybrid QM/MM calculations using the IMOMM method. The roles of the diphosphine bite angle and of the nonbonding interactions were analyzed in detail by considering rhodium systems containing xantphos-type ligands, for which a correlation between the natural bite angle and regioselectivity has been recently reported. From the pentacoordinated equatorial--equatorial HRh(CO)(alkene)(diphosphine) key intermediate, eight possible reaction paths were defined and characterized through their respective transition states (TS). We succeeded in reproducing the experimentally observed trends for the studied diphosphines. By performing additional calculations on model systems, in which the steric effects induced by the phenyl substituents of xantphos ligands were canceled, we were able to separate, identify, and evaluate the different contributions to regioselectivity. These additional calculations showed that regioselectivity is governed by the nonbonding interactions between the diphenylphosphino substituents and the substrate, whereas the effects directly associated to the bite angle, what we call orbital effects, seem to have a smaller influence.     

Palladium-diphosphite catalysts for the asymmetric allylic substitution reactions

[structure: see text] We have designed a series of diphosphite ligands to study the effect of the backbone, the size of the chelate ring, and the substituents of the biphenyl moieties and to determine the scope of this type of ligand in the Pd-catalyzed asymmetric substitution reactions of different types of substrates. Good-to-excellent activities and enantioselectivities have been obtained for disubstituted linear substrate 11 (TOF's up to >2000 mol x (mol x h)(-1), ee values up to 99%) and cyclic substrate 14 (TOF up to 285 mol x (mol x h)(-1), ee values up to 92%). However, these ligands are inadequate for the Pd-catalyzed allylic alkylation of monosubstituted linear substrates because they provide low enantioselectivities.     

Ligand‐Controlled Regiodivergent Enantioselective Rhodium‐Catalyzed Alkene Hydroboration

Regiocontrol in the rhodium‐catalyzed boration of vinyl arenes is typically dominated by the presence of the conjugated aryl substituent. However, small differences in TADDOL‐derived chiral monophosphite ligands can override this effect and direct rhodium‐catalyzed hydroboration of β‐aryl and β‐heteroaryl methylidenes by pinacolborane to selectively produce either chiral primary or tertiary borated products. The regiodivergent behavior is coupled with enantiodivergent addition of the borane. The nature of the TADDOL backbone substituents and that of the phosphite moiety function synergistically to direct the sense and extent of regioselectivity and enantioinduction. Twenty substrates are shown to undergo each reaction mode with regioselectivity values reaching greater than 20:1 and enantiomer ratios reaching up to 98:2. A variety of subsequent transformations illustrate the potential utility of each product.     

Asymmetric allylic substitutions on symmetrical and non-symmetrical substrates using [5]ferrocenophane ligands

A series of [5]ferrocenophane diphosphane ligands were used in Pd-catalyzed allylic substitution reactions. With a symmetrical substrate, 1,3-diphenylpropenyl acetate, enantioselectivities between 70% and 94% ee were observed. Several non-symmetrically substituted allylic substrates were also used. Depending on the substituents of the non-symmetrical allylic substrates, various degrees of regioselectivity (from 1:1 to 100:0) and enantioselectivity (from 0% to 96% ee) were observed. Tentative catalytically active complexes were studied by DFT computational methods.     

Highly regioselective isomerization-hydroformylation of internal olefins to linear aldehyde using rh complexes with tetraphosphorus ligands

A series of new pyrrole-based tetraphosphorus ligands were synthesized and used for Rh-catalyzed isomerization-hydroformylation of internal olefins. It was found that the substituents at the 3,3',5,5'-positions of the biphenyl greatly effected the linear selectivity, and the alkyl-substituted tetraphosphorus ligands gave the best results (for 2-octene, n: i up to 207, for 2-hexene, n: i up to 362).     

Pd-catalysed methoxycarbonylation of vinylarenes using chiral monodentate phosphetanes and phospholane as ligands. Effect of substrate substituents on enantioselectivity

Palladium complexes bearing phospholane 1 and phosphetane 2-4 ligands have been synthesised to be used as catalyst precursors in the asymmetric methoxycarbonylation of vinyl arenes. Single crystals of the complex [PdCl2(2)2] II were obtained from a toluene solution and analysed by X-ray crystallography. Using these complexes, excellent regioselectivity (up to 99%) to the branched esters was obtained. Phosphetane ligands provide higher enantioselectivity than the phospholane under the same reaction conditions and an important influence of the substrate was observed. Enantioselectivity up to 50% was obtained using 4-methoxystyrene.     

Transition‐State Stabilization by a Secondary Substrate–Ligand Interaction: A New Design Principle for Highly Efficient Transition‐Metal Catalysis

A library of monodentate phosphane ligands, each bearing a guanidine receptor unit for carboxylates, was designed. Screening of the library gave some excellent catalysts for regioselective hydroformylation of β,γ‐unsaturated carboxylic acids. A terminal alkene, but‐3‐enoic acid, was hydroformylated with a linear/branched (l/b) regioselectivity up to 41. An internal alkene, pent‐3‐enoic acid was hydroformylated with regioselectivity up to 18:1. Further substrate selectivity (e.g., acid vs. methyl ester) and reaction site selectivity (monofunctionalization of 2‐vinylhept‐2‐enoic acid) were also achieved. Exploration of the structure–activity relationship and a practical and theoretical mechanistic study gave us an insight into the nature of the supramolecular guanidinium–carboxylate interaction within the catalytic system. This allowed us to identify a selective transition‐state stabilization by a secondary substrate–ligand interaction as the basis for catalyst activity and selectivity.     

Highly active rhodium/phosphorus catalytic system for the hydroformylation of α-methylstyrene

Rhodium catalyzed hydroformylation of a-methylstyrene was investigated in the presence of monodentate phosphine ligands L1–L6. We found that the phosphine with good p-acceptability could efficiently improve the activity of the a-methylstyrene hydroformylation. The big steric hindrance of a-C in a-methylstyrene enhanced the regioselectivity towards the linear aldehyde, which resulted in3-phenylbutanal as the predominant product(99.0%). When tris(N-pyrrolyl)phosphine(L1) modified Rh(acac)(CO)_2was employed as the catalyst, the TOF could reach up to 5786 h~(-1)in the a-methylstyrene hydroformylation at relatively mild conditions(110 8C, 6 MPa).     

Novel rhodium catalyst for asymmetric hydroformylation of styrene: Study of electronic and steric effects of phosphorus seven-membered ring ligands

The asymmetric hydroformylation of styrene catalysed by rhodium complexes modified by monodentate phosphepine ligands has been investigated. The effects of a systematic variation of the phosphorus substituent on catalytic activity and selectivity are reported as well as the outcome of a combinatorial approach for the formation of mixed ligands complexes with several commercially available ligands. Effective catalytic systems have been devised for the reaction that provide for full conversion within 24 h and regioselectivity up to 96% in the branched aldehyde and enantioselectivities up to 48%. The use of bidentate ligands built up by binaphthyl-supported seven-membered phosphacyclic units does not allow for further improvement in the reaction outcome.     

Rhodium/bisphosphite catalytic system for hydroformylation of styrene and its derivatives

Different kinds of mono‐ and bidentate phosphite ligands were used in Rh‐catalyzed hydroformylation of styrene to illustrate the influence of steric and electronic properties of ligands on catalytic performance. High activity (99.9%) and good regioselectivity (85.4%) to the linear aldehyde were achieved under optimum conditions in the presence of Rh/bisphosphite complex (bisphosphite: 2,2′‐bis(dipyrrolylphosphinooxy)‐1,1′‐(±)‐binaphthyl). This system makes it possible to prepare functionalized terminal aldehydes from readily available styrene or its derivatives through hydroformylation with high linear selectivity. Copyright © 2013 John Wiley & Sons, Ltd.     

Rh-catalyzed asymmetric hydrogenation using a furanoside monophosphite second-generation ligand library: scope and limitations

The ligand design of one of the most successful monophosphite ligand classes in Rh-catalyzed hydrogenation was expanded upon by introducing several substituents at the C-3 position of the furanoside backbone. A small but structurally important library of monophosphite ligands was developed by changing the substituents at the C-3 position of the furanoside backbone and the substituents/configurations at the biaryl phosphite group. These new furanoside monophosphite ligands were evaluated in the Rh-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acid derivatives and enamides. The results show that the effect of introducing a substituent at the C-3 position of the furanoside backbone on the enantioselectivity depends not only on the configuration at the C-3 position of the furanoside backbone and the binaphthyl group but also on the substrate. Thus, the new ligands afforded high to excellent enantioselectivities in the reduction of carboxylic acid derivatives (ee’s up to >99.9%) and moderate ee’s (up to 67%) in the hydrogenation of enamides.     

Highly selective hydroaminomethylation of internal alkenes to give linear amines

The application of phenoxaphosphino-modified Xantphos-type ligands (1-9) in the rhodium-catalyzed hydroaminomethylation of internal olefins to give linear amines is reported. Excellent chemo- and regioselectivities have been obtained through the use of 0.1 mol % [Rh(cod)2]BF(4)/0.4 mol % xantphenoxaphos (1), providing a practical and environmentally attractive synthetic route for the preparation of amines from internal alkenes. For the first time, both functionalized internal olefins and mixtures of internal and terminal olefins have been converted highly selectively into linear amines. Investigations of the effects of the calculated natural bite angles of ligands on hydroaminomethylation shows that the regioselectivity for the linear product follows a similar trend to that seen in the hydroformylation of internal alkenes with the aid of these ligands. Hydroaminomethylation and each of its individual steps were monitored by high-pressure infrared spectroscopy. The results suggest that hydroaminomethylations take place by a sequential isomerization/hydroformylation/amination/hydrogenation pathway.     

Synthesis and Application of Modular Phosphine–Phosphoramidite Ligands in Asymmetric Hydroformylation: Structure–Selectivity Relationship

A series of hybrid phosphine–phosphoramidite ligands has been designed and synthesized in moderate yields from chiral BINOL (1,1′‐bi‐2‐naphthol) or NOBIN (2‐amino‐2′‐hydroxy‐1,1′‐binaphthyl). They have achieved highly regio‐ and enantioselectivities in Rh‐catalyzed asymmetric hydroformylations of styrene derivatives (branched/linear ratio up to 56.6, ee up to 99 %), vinyl acetate derivatives (up to 98 % ee), and allyl cyanide (up to 96 % ee). Systematic variation of ligand structure showed that the steric factor on the phsophoramidite moiety determined the performance of the ligand. With the increased hindrance, the branched/linear ratio rose, while the ee value dropped in the hydroformylation of styrene. However, the N‐substituents did not influence the selectivities much.     

Highly regio- and enantioselective Heck reaction of N-methoxycarbonyl-2-pyrroline with planar chiral diphosphine-oxazoline ferrocenyl ligands

[reaction: see text] A series of planar chiral diphosphine-oxazoline ferrocene ligands were effectively applied in the asymmetric arylation of N-methoxycarbonyl-2-pyrroline, and up to 99% ee was observed for the product 3. The regioselectivity of this reaction was strongly affected by the different precursors of the palladium species and the polarity of the solvent.     

New P,N-ferrocenyl ligands for rhodium-catalyzed hydroboration and palladium-catalyzed allylic alkylation

A set of nine new chiral P,N-ferrocenyl ligands for metal-catalyzed enantioselective reactions has been prepared. The rhodium-catalyzed hydroboration of styrene with catechol borane proceeded with high regioselectivity (up to 97:3) or with high enantioselectivity (up to 92% ee) depending on the catalyst. Good results were also obtained in the palladium-catalyzed asymmetric alkylation of 1,3-diphenylallylic systems (up to 94% ee).     

钯催化芳香硝基化合物与烯烃的选择性还原羰化酰胺化反应

与芳香胺相比,芳香硝基化合物具有廉价易得、官能团兼容性好等优点,作为氮源在下游含氮化学品合成中具有广泛的应用.目前烯烃羰化酰胺化反应绝大多数以胺类化合物为氮源,其中直链和支链酰胺产物的选择性主要是通过具有特定电子和位阻特性的配体调控实现.已报道的芳香硝基化合物的还原酰胺化反应研究中,需要外加还原剂或者利用金属羰基化合物Mo(CO)6释放的CO为羰基源和还原剂.本文发展了一种毋须外加还原剂的钯催化芳香硝基化合物与烯烃的还原羰化酰胺化反应新方法.研究发现,钯金属催化剂(特别是离子型)的抗衡阴离子是还原羰化酰胺化反应中化学选择性和羰化区域选择性的关键因素.抗衡阴离子为氯离子、硼酸为助剂时,最优钯前驱物K2PdCl4的产物主要为支链酰胺,此时不同的膦配体并不能调控其区域选择性,这与胺的烯烃酰胺化反应可以通过配体调控羰化的区域选择性表现出明显的不同.含氮中间体原位捕捉、硝基化合物还原下游可能中间体对照实验等研究表明,芳香硝基化合物在以一氧化碳为还原剂的催化还原体系下被完全脱氧还原为氮烯(Ar-N:),再经过烯酰胺中间体进一步烯键还原得到相应的支链酰胺;当离子型钯前驱物的抗衡阴离子配位性较弱时,最优钯前驱物为Pd(CH3CN)4(OTf)2时,以直链酰胺为主要产物,此时不同的膦配体可以调控酰胺化的区域选择性.同样的机理研究表明,在该催化剂体系下芳香硝基化合物首先被还原为芳基胺,然后再发生与现有报道类似的胺类化合物的烯烃羰化酰胺化反应.这两个催化反应体系都表现出了较好的底物适用性,并且可以高效地应用于除草剂(敌稗)的一步合成.本文为以硝基化合物为起始氮源,通过催化控制生成特定含氮中间体,从而可控合成不同的含氮化学品提供了一条新思路.     

Linear-selective hydroformylation of vinyl ether using Rh (acac)(2,2′-bis{(di[1H-indol-1-yl]phosphanyl)oxy}-1,1′-binaphthalene) – Possible way to synthesize 1,3-propanediol

Three bidentate phosphoramidite ligands were synthesized, characterized, and employed in Rh-catalyzed hydroformylation of vinyl ethers. The complex Rh(acac)(2,2′-bis{(di[1H-indol-1-yl]phosphanyl)oxy}-1,1′-binaphthalene} (acac = acetylacetone) (Rh- L4 ) was also synthesized and characterized. Rh- L4 showed good regioselectivity for the hydroformylation of vinyl ethers under mild reaction conditions: 2 MPa of syngas, 1:1 (H₂/CO) substrate/catalyst molar ratio 1000:1, and 60 °C. The linear selectivity was up to 98%, and in most cases was about 80%, with no hydrogenation product formation observed, which could be a potential way to synthesize 1,3-propanediol. A mechanism study including density functional theory computational analysis showed that both Rh–H and CO insertion steps in the hydroformylation of vinyl ether were linear-preferred in our catalyst system.