From chiral and prochiral N-allylpyrroles to stereodefined pyrrole fused architectures: A particular application of the rhodium-catalyzed hydroformylation

We review our recent results on the rhodium-catalyzed hydroformylation of chiral and prochiral N-allylpyrroles as a synthetic route to stereodefined 5,6-dihydro- and 5,6,7,8-tetrahydroindolizines. The indolizine nucleus at different degrees of unsaturation is a building block of natural and synthetic target compounds; thus new approaches, especially if stereoselective and/or stereospecific, are highly desirable. The construction of the indolizine architectures reported here occurs by formation of a C8-C9 bond through intramolecular cyclization of the 4-pyrrolylbutanal intermediate.     

4-甲基吡咯并[2,1,5-cd]中氮茚的合成

以2-乙基吡啶生成的叶立德为原料,采用1,3-偶极环加成反应,得到了一系列3-乙酰基(或苯甲酰基)-5-乙基中氮茚衍生物,后者与KOH在加热条件下发生分子内缩合,得到了一系列4-甲基吡咯并[2,1,5-cd]中氮茚.     

Domino reaction sequences in the rhodium-catalyzed hydroformylation of 3-acetyl-1-allylpyrrole: a short route to 5,6,7,8-tetrahydroindolizines

When 3-acetyl-1-allylpyrrole (1) was subjected under hydroformylation conditions, with Rh₄(CO)₁₂ as catalyst precursor, to 30 atm CO/H₂ (1:1) total pressure and 140 °C, an equimolar mixture of the isomeric 5,6,7,8-tetrahydroindolizines 4′ and 5′ was obtained as the almost exclusive product. In both cases a domino hydroformylation/cyclization on the α pyrrole positions by the aldehyde 3 carbonyl group occurs which involves different intermediates: while 4′ is generated via the dihydroindolizine 4, 5′ forms via direct reduction of 8-hydroxytetrahydroindolizine 5, a structure that has never been observed before from 1-allylpyrroles under oxo conditions.     

Synthesis of new o-alkyl substituted arylalkylphosphanes: study of their molecular structure and influence on rhodium-catalyzed propene and 1-hexene hydroformylation

A set of new phosphane ligands designed to increase the branched-to-normal ratio of the hydroformylation reaction were prepared in the same way as the previously reported ortho-alkyl substituted arylphosphanes, which have shown increased i/n ratios in the hydroformylation of propene and 1-hexene. In order to determine the relationship between the catalytic behavior and stereoelectronic properties of the ligands, various functional alkyl groups (methyl, isopropyl, cyclohexyl) were placed on the phosphorus atom directly and in the ortho position of the phenyl ring connected to phosphorus. In the hydroformylation reaction of propene and 1-hexene a higher i/n ratio resulted with nearly all the ligands compared with that of triphenylphosphane. Additionally as the ortho-alkyl-substituent became larger, it had a favorable effect on the i-selectivity. Characterization of the ligands was carried out by NMR spectroscopy (mainly ¹H, ³¹P{¹H}, ¹³C{¹H}, HSQC/HETCOR and COSY-90). Properties of the ligands were also studied by quantum mechanical calculations and by synthesizing three Rh(acac)(CO)(PR₃) derivatives. The o-alkyl-substituent was orientated outside the ligands’ cone angle in the X-ray crystal structures of (2-cyclohexylphenyl)dicyclohexylphosphane and (2,5-dimethylphenyl)bis(4-pyridyl)phosphane, and Rh(acac)(CO)(PR₃) complex of (2-methylphenyl)dicyclohexylphosphane.     

Phosphinoethyl-sulfonatoalkylthioethers and diphenyl-ω-sulfonatoalkyl-phosphines as ligands and polyoxyethylene–polyoxypropylene–polyoxyethylene triblock co-polymers as promoters in the rhodium-catalyzed hydroformylation of 1-dodecene in aqueous two-phase systems

The rhodium-catalyzed hydroformylation of 1-dodecene was investigated with a series of sulfonated water-soluble phosphine ligands at a pressure of 60 bar CO/H₂ and a temperature of 120 °C. Seven different groups of water-soluble phosphines were used for our investigations. We established an optimized ligand/rhodium ratio of 5 for the phosphines 1a, [Ph₂P(CH₂)₂S(CH₂)₂SO₃Na], and 1b, [Ph₂P(CH₂)₂S(CH₂)₃SO₃Na]. The utilized arylphosphino-thioether-alkylsulfonates formed with Rh(I) compounds highly active catalysts which could be recycled. The addition of detergents speeds up the hydroformylation reaction, but disturbs the phase separation (recycling). The best promotion effect and the smallest negative influence on phase separation gave polyoxyethylene–polyoxypropylene–polyoxyethylene triblock co-polymers. The ratio of 1-dodecene/rhodium could be increased up to 10.000 and we achieved turnover numbers (TONs)>50.000 without any surfactant and TONs of about 65.000 in presence of the co-polymers owing to the recycling on the catalytic system.     

Desulfitative palladium‐catalyzed direct C‐3 arylation of indolizines with arylsulfonyl chlorides

An efficient Pd‐catalyzed desulfitative approach to C‐3 arylation of indolizine derivatives has been developed, and the protocol uses readily available arylsulfonyl chlorides as the arylation reagent under nitrogen. This transformation was performed in a mixed solvent of 1‐methyl‐2‐pyrrolidone and dimethoxyethane using simple triphenylphosphine as a ligand, which provides a new method for the C‐3 arylation of indolizines. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of monofluorinated indolizines and their derivatives by the 1,3-dipolar reaction of N-ylides with fluorinated vinyl tosylates

Monofluorinated indolizines 4, benzo[d]indolizines 7 and 4H-pyrrolo[1,2-a]benzimidazoles 8 were synthesized in moderate yields by 1,3-dipolar reaction between fluorinated vinyl tosylates 2a and N-ylides of pyridinium, isoquinolinium and benzimidazolinium, generated in situ from their halides salts. When the same N-ylides were allowed to react with 2,3,3-trifluoro-1-propenyl tosylate 2b, the unexpected product formylated indolizines and their derivatives 9 were obtained. The reaction mechanism is also proposed.     

Phosphabarrelenes as ligands in rhodium-catalyzed hydroformylation of internal alkenes essentially free of alkene isomerization

Despite significant research efforts in the past, one of the remaining problems to be solved in industrially important hydroformylation is the chemoselective low-pressure hydroformylation of internal alkenes. We report here on a new class of phosphabarrelene/rhodium catalysts 2 that display very high activity towards hydroformylation of internal alkenes with an unusually low tendency towards alkene isomerization. Preparation of new phosphabarrelene ligands, studies of their coordination properties, as well as results obtained in the rhodium-catalyzed hydroformylation of cyclic and acyclic internal alkenes are reported.     

A further breakthrough in biphasic, rhodium-catalyzed hydroformylation: the use of Per(2,6-di-O-methyl)-β-cyclodextrin as inverse phase transfer catalyst

Solvent free biphasic hydroformylalion of various water-insoluble terminal olefins can be achieved in high yields and sclcctivitics by using a water-soluble rhodium/triphenylphosphine trisulfonate catalyst and per(2,6-di-o-mclhyl)-β-cyclodcxtrin as inverse phase transfer catalyst. The catalytic activities were up to ten times higher than those observed without pcr(2,6-di-o-methyl)-β-cyclodextrin.     

Synthesis,characterization and evaluation of heterobimetallic Fe(II)/Rh(I) and Fe(II)/Ru(II) complexes as catalyst precursors for hydroformylation of 1-octene

Abstract

Two new ferrocenyl iminopyridyl ligands, L1 and L2, have been synthesized and characterized using spectroscopic and analytical techniques. Both ligands were used to prepare new Rh(I) and Ru(II) ferrocenyl complexes 1–4. The structures of the complexes were confirmed using ¹H and ¹³C nuclear magnetic resonance spectroscopy, high resolution electrospray ionization mass spectrometry, and infrared spectroscopy. The complexes were tested as catalysts in the hydroformylation of 1-octene. Rh ferrocenyl complexes 1 and 4 produced aldehydes under mild conditions while the Ru-ferrocenyl complexes 2 and 3 required higher temperature and pressure for effective hydroformylation to occur. The catalysts display excellent aldehyde chemoselectivity with varying regeoselectivity depending on temperature and pressure conditions employed. At high temperatures, the Rh ferrocenyl precatalysts favor formation of branched aldehydes due to increased isomerization at high temperatures. The Ru ferrocenyl precatalysts displayed less hydroformylation activity; however, the complexes show good chemoselectivity for aldehydes with no hydrogenation products formed.     

Rhodium catalysed hydroformylation of unsaturated esters

Rhodium catalysed hydroformylation of unsaturated esters has been studied. A pronounced temperature dependence was observed on the regioselectivity and catalytic activity for these reactions, and under the appropriate conditions, it is possible to obtain preferentially either linear or quaternary products. A quaternary selective hydroformylation of methyl atropate to give 1,3-aldehydic esters has also been developed.     

Rhodium phosphine complexes immobilized on silica as active catalysts for 1-hexene hydroformylation and arene hydrogenation

In immobilizing the rhodium complexes [Rh(acac)(CO)(P)] (1) and [Rh(acac)(P)₂] (2) (P = Ph₂PCH₂CH₂Si(OMe)₃) onto SiO₂, acetylacetone is found to be released through protonation of the acac ligand by the acidic silica-OH groups. The resulting complexes [Rh(O-{SiO₂}(HO-{SiO₂})(CO)(P-{SiO₂})] (1a) and [Rh(O-{SiO₂})(HO-{SiO₂})(P-{SiO₂})₂] (2a) were successfully tested with respect to their catalytic action on 1-hexene hydroformylation as well as benzene and toluene hydrogenation. The reaction outcome, viz. the formation of aldehydes versus isomerization, depends strongly on the presence and concentration of a phosphine co-catalyst. Thus, while 1a gave only a 17% yield of aldehyde in the absence of phosphines, the yield is increased to 54% in the presence of phosphinated silica P-{SiO₂} or even 94% if PPh₃ is added to the solution. Without extra added phosphine, both 1a and 2a effect mainly the isomerization of 1-hexene to 2-hexene. Pre-catalyst 1a catalyzes also the hydrogenation of benzene at 10.5 atm H₂ and 90 °C to give cyclohexane with a TOF of 608 h⁻¹.     

Comparison of a range of rhodium-based catalysts for the hydroformylation of selected alkenes

Four rhodium-based catalyst systems 1, 2, 3, and [Rh(OAc)₂]₂/PPh₃ have been used in the hydroformylation of 1-hexene, styrene and some phosphino-, amino- and amido-alkenes. In general the catalysts showed very similar reactivity and selectivity.     

An alternative synthesis of the lipophilic tail portion of abediterol using linear-selective hydroformylation

Abediterol is a compound currently in development for the treatment of respiratory disease at AstraZeneca. In this work we employ hydroformylation, an under-utilised reaction in the synthesis of pharmaceutical intermediates, as a key step to access the lipophilic amine portion of this molecule. The route described herein addresses some of the issues identified in the original route. Namely, hazardous materials are avoided and increased levels of control – from a process chemistry point of view – are demonstrated, with isolation of intermediates possible at multiple points in the synthesis. This work provides ‘proof-of-concept’ for an alternative synthetic route and provides high-quality material using a series of robust transformations.     

铑-三苯基膦配合物功能化的聚合物@介孔氧化硅复合材料在1-辛烯氢甲酰化反应中的应用(英文)

通过在介孔氧化硅材料中原位聚合的方法制备了三苯基膦功能化的有机聚合物@介孔氧化硅复合材料PPh3polymer@FDU-12.采用X射线衍射、氮气吸附脱附、透射电镜和热重等手段对其结构和组成进行了表征.该复合材料与金属前驱体Rh(acac)(CO)2配位后得到的固体催化剂,在长链烯烃1-辛烯的氢甲酰化反应中,醛选择性可达92%–96%,并表现出高于聚合物的活性(99%转化率).这主要归因于介孔氧化硅材料的高比表面积和有序的孔结构更有利于反应物和催化活性中心的接触.研究发现,调变复合材料中聚合物的含量或使用不同孔道结构的氧化硅载体(SBA-15,MCM-41和FDU-12)都会影响固体催化剂的反应活性和选择性.该方法得到的多相催化剂具有较好的循环使用性能,在循环使用15次后仍能保持较好的反应活性,但醛选择性有所降低.     

Synthesis of 2-chromanol by hydroformylation of 2-hydroxystyrene derivatives

2-Benzyloxy- and 2-tosyloxystyrene were hydroformylated under different reaction conditions with the aim to obtain the corresponding linear aldehydes, valuable intermediates to 2-chromanol, a structural moiety present in several interesting therapeutically active molecules. The best results were obtained by using the catalytic precursor Pt(Xantphos)Cl₂ in toluene or the water-soluble catalytic system Rh(CO)₂acac/Xantphos(SO₃Na)₂ in the biphasic medium water/toluene. Rather good regioselectivities were also achieved employing the unmodified complex Rh₄(CO)₁₂ at high temperature and low pressure for very short reaction times: unfortunately the chemoselectivity of the process was not satisfactory, due to the extensive formation of the substrate hydrogenation product.     

Platinum complexes of 2-diphenylphosphinobenzaldehyde-derived P-alkene ligands and their application in the hydroformylation of styrene

Neutral complexes of the formula PtCl₂L₂ (where L = diethyl 2-diphenylphosphino-benzylidene-malonate (1), diisopropyl 2-diphenylphosphino-benzylidene-malonate (2), di-tert-butyl 2-diphenylphosphino-benzylidene-malonate (3), methyl E-2-(2′-diphenylphosphinophenyl)-acrylate (4), tert-butyl E-2-(2′-diphenylphosphinophenyl)acrylate (5)) were prepared. These complexes proved to be excellent precursors to active catalysts for the hydroformylation of styrene. The platinum-containing catalytic systems prepared from malonate-based ligands 1 and 2 provided the highest activity. Chemoselectivities of up to 87% were obtained, while the two aldehyde regioisomers were formed in almost equimolar ratio. The in situ studies by using lower ligand to Pt ratios resulted in slight decrease in both regio- and chemoselectivities.³¹P NMR studies on the PtCl₂L₂ complexes revealed that the formation of trans isomers is highly preferred in the case of benzylidene malonate-type ligands with two ester functionalities (1-3) probably due to steric hindrance. A mixture of cis/trans geometrical isomers (on the Pt) with a predominance of the trans isomer was formed when acrylate-type ligands with one ester functionality (4 and 5) were used.