Tetrakis[(4S)-4-phenyloxazolidin-2-one]dirhodium(II) and Its Catalytic Applications for Metal Carbene Transformations

The synthesis and X-ray structure of the binuclear complex tetrakis[(4S)-4-phenyloxazolidin-2-one]-dirhodium(II) ([Rh₂{(4S)-phox}₄]) are reported. Structure-selectivity comparisons are made for typical metal carbene transformations, such as inter- and intramolecular cyclopropane formation, intermolecular cyclopropene formation and intramolecular C–H insertions of diazoacetates and diazoacetamides. The enantioselectivity achieved in the [Rh₂{(4S)-phox}₄]-catalyzed reactions is intermediate between that of [Rh₂{(5S)-mepy}₄] and [Rh₂{(4R)-bnox}₄], which were described previously (mepy = methyl 5-oxopyrrolidine-2-carboxylate; bnox = 4-benzyloxazolidin-2-one). In contrast to other catalyzed intermolecular cyclopropane formations, those using [Rh₂{(4S)-phox}₄] result preferentially in formation of the cis-cyclopropane.     

Enantioselective Formation of Bicyclic Lactones by Rhodium-Catalyzed Intramolecular CH-insertion reactions

The decomposition of cyclohexyl diazoacetate ( 5a ) in the presence of the chiral [Rh₂{(2S)-mepy}₄] catalyst leads to a 3:1 cis/trans mixture of bicyclic lactone 6a with an enantiomeric excess of 95–97% (cis) and 90% (trans). The conformationally rigid tert-butyl derivatives 5b and 5c afford, in the presence of the same catalyst, 6b and 6c , respectively, via insertion into the equatorial C? H bonds exclusively, with ee's of ca. 95%. A remarkable degree of induction (92–95%) results in the lactone 6g upon decomposition of 1-isopropyl-2-methylpropyl diazoacetate ( 5g ). The diazoacetates derived from 1-methylcyclohexanol, cyclopentanol and 1-methylcyclopentanol ( 5d–f ) afford under similar conditions insertion products with higher diastereoselectivity, but significantly lower enantioselectivity. Other dirhodium catalysts are less efficient.     

cis-Disubstituted Cyclopropanes via Asymmetric Catalytic Cyclopropenation: Synthesis of Cyclopropyl-dehydroamino Acids and of Dictyopterene C′

The cyclopropenation of diethoxypropyne ( 1 ) with methyl diazoacetate in the presence of [Rh₂{(2S)-mepy}₄] (mepy=methyl 5-oxopyrrolidine-2-carboxylate) proceeds with >95% ee. The resulting cyclopropenecarboxylate 2 underwent stereoselective hydrogenation to the cis-cyclopropane 3 . Hydrolysis of the acetal function of 3 liberated the formyl cyclopropenecarboxylate 4 , which was transformed by Wittig reaction with the phosphonate 5 to afford dehydroamino acid 6 as a mixture of (Z)- and (E)-isomers in various proportions. The (Z)-isomer 6a was hydrolyzed, and the structure and the absolute configuration of the (Z)-dicarboxylic acid 7a were established by X-ray crystallography. The cis-divinylcyclopropane 11 (ee>95%), in turn, was synthesized from 4 via Wittig reaction to afford 8 , which was transformed to the aldehyde 10 and subjected to a second Wittig reaction. Thermolysis of 11 afforded (+)-dictyopterene C′ ( 12 ) in quantitative yield.     

Parallel Kinetic Resolution Approach to the Cyathane and Cyanthiwigin Diterpenes Using a Cyclopropanation/Cope Rearrangement

Parallel effort : Stereodivergent parallel kinetic resolution of a racemic mixture of dienes using Davies' [Rh₂{(S)‐dosp}₄] or [Rh₂{(R)‐dosp}₄] catalysts promotes a tandem vinyl diazoacetate cyclopropanation/Cope rearrangement sequence to afford two diastereomeric, enantioenriched cycloheptadienes, which correspond to the natural antipodes of the title diterpenoids (see scheme).

     

Diastereoselective rhodium-catalyzed nitrene transfer starting from chiral sulfonimidamide-derived iminoiodanes

The dirhodium-catalyzed aziridination of olefins with chiral sulfonimidamides as iminoiodane precursors has been investigated under stoichiometric conditions. Diastereoisomeric excesses of up to 82% have been achieved using [Rh₂{(S)-nttl}₄] as catalyst. Matching and mismatching effects were observed upon use of chiral rhodium(II) carboxylate catalysts.     

Synthesis and Characterization of Chiral Bis(aminato)iridate(I) and Aminato‐Bridged Iridium(I) Complexes

The two dinuclear Ir^I complexes [Ir₂(μ‐Cl)₂ {(R)‐(S)‐PPF‐PPh₂}₂] ( 1 ; (R)‐(S)‐PPF‐PPh₂=(S)‐1‐(diphenylphosphino)‐2‐[(R)‐1‐(diphenylphosphino)ethyl]ferrocene and [Ir₂(μ‐Cl)₂{(R)‐binap}₂] ( 3 ; (R)‐binap=(R)‐[1,1′‐binaphthalene]‐2,2′‐diylbis[diphenylphosphine]) smoothly react with 4 equiv. of the lithium salt of aniline to afford the new bis(anilido)iridate(I) (=bis(benzenaminato)iridate(1‐)) complexes Li[Ir(NHPh)₂{(R)‐(S)‐PPF‐PPh₂}] ( 4 ) and Li[Ir(NHPh)₂{(R)‐binap}] ( 5 ), respectively. The anionic complexes 4 and 5 react upon protonolysis to give the dinuclear aminato‐bridged derivatives [Ir₂(μ‐NHPh)₂{(R)‐(S)‐PPF‐PPh₂}₂] ( 6 ) and [Ir₂(μ‐NHPh)₂{(R)‐binap}₂] ( 7 ), which were characterized by X‐ray crystallography. None of the new complexes 4 – 7 shows catalytic activity in the hydroamination of olefins.     

Intramolecular Asymmetric Amidations of Sulfonamides and Sulfamates Catalyzed by Chiral Dirhodium(II) Complexes

Enantioselective intramolecular amidation of aliphatic sulfonamides was achieved for the first time by means of chiral carboxylatodirhodium(II) catalysts in conjunction with PhI(OAc)₂ and MgO in high yields and with enantioselectivities of up to 66% (Scheme 3, Table 1). The best results were obtained with [Rh₂{(S)‐nttl)₄] and [Rh₂{(R)‐ntv)₄] as catalysts ((S)‐nttl=(αS)‐α‐(tert‐butyl)‐1,3‐dioxo‐2H‐benz[de]isoquinoline‐2‐acetato, (R)‐nto=(αR)‐α‐isopropyl‐1,3‐dioxo‐2H‐benz[de] isoquinoline‐2‐acetato). In addition, these carboxylatodirhodium(II) catalysts were also efficient in intramolecular amidations of aliphatic sulfamates esters, although the enantioselectivity of these latter reactions was significantly lower (Scheme 4, Table 3).     

Carbenoid Reactions in Rhodium(II)-Catalyzed Decomposition of Iodonium Ylides

The intermediacy of metallocarbenes in decomposition reactions of iodonium ylides with [Rh₂(OAc)₄] was established by comparison with reactions of the corresponding diazo compounds. The sensitivity of the Rh^II-catalyzed intermolecular cyclopropane formation from substituted styrenes and bis(methoxycarbonyl)(phenyliodono)methanide ( 1a ) or dimethyl diazomalonate ( 1b ) is identical. The Hammett plot (with σ⁺) has a slope of ?0.47. Iodonium ylides and diazo compounds afford the same products in [Rh₂(OAc)₄]-catalyzed cyclopropane formations, cycloadditions, and intramolecular CH insertions, and exhibit the identical selectivity in intramolecular competitions for cyclopropane formation and insertion. The intramolecular CH insertion of the ylide 20c , when carried out in the presence of a chiral catalyst ([Rh₂{(?)-(S)-ptpa}₄]), results in formation of 21a having an ee of 67%, identical to the ee obtained with the diazo compound 20b .     

Reactions of Diazo Compounds with Imines. Preliminary communication

The [Rh₂(OAc)₄]-catalyzed addition of methyl diazoacetate to N-benzylideneaniline ( 1a ) afforded the imine cis- 2 in 35% yield. Under catalysis by chiral Rh^II catalysts, however, only racemic 1a was produced, and the yield was low. In the presence of dimethyl maleate, aziridine formation was suppressed, and an intermediate ylide 6 was trapped as cycloadduct 7 . No aziridines were obtained, however, from 1b, 1c , and 3 . The iminium salt 8 reacted with (trimethylsilyl)diazomethane in the absence of [Rh₂(OAc)₄] via dipolar cycloaddition followed by extrusion of N₂ to 10 .     

The Enantioselectivity and the Stereochemical Course of Copper‐Catalyzed Intramolecular CH Insertions of Phenyliodonium Ylides

The Cu‐catalyzed intramolecular CH insertion of phenyliodonium ylide 1b was investigated at 0° in the presence of several chiral ligands. Enantioselectivities varied in the range 38–72%, and were higher than those resulting from reaction of the diazo compound 1c at 65°. The intramolecular insertion of the enantiomerically pure methyl diazoacetate (R)‐ 20 and of the corresponding phenyliodonium ylide (R)‐ 21 proceeded to (R)‐ 23 with retention of configuration with [Cu(hfa)₂] (hfa=hexafluoroacetylacetone=1,1,1,5,5,5‐hexafluoropentane‐2,4‐dione) and [Rh₂(OAc)₄]. These results are consistent with a carbenoid mechanism for the Cu‐catalyzed insertion with phenyliodonium ylides. However, the insertion of the perfluorosulfonated phenyliodonium ylide (R)‐ 29 afforded with [Cu(hfa)₂] as well as with [Rh₂(OAc)₄] the cyclopentanone derivative 30 as a cis/trans mixture with only 56–67% enantiomeric excess.     

Rhodium‐Catalyzed Stereoselective Amination of Thioethers with N‐Mesyloxycarbamates: DMAP and Bis(DMAP)CH2Cl2 as Key Additives

A stereoselective Rh‐catalyzed intermolecular amination of thioethers using a readily available chiral N‐mesyloxycarbamate to produce sulfilimines in excellent yields and diastereomeric ratio is described. A catalytic mixture of 4‐dimethylaminopyridine (DMAP) and bis(DMAP)CH₂Cl₂ proved pivotal in achieving high selectivity. The X‐ray crystal structure of the (DMAP)₂?[Rh₂{(S)‐nttl}₄] complex was obtained and mechanistic studies suggested a Rh^II‐Rh^III complex as the catalytically active species.     

Design and Synthesis of Novel Chiral Dirhodium(II) Carboxylate Complexes for Asymmetric Cyclopropanation Reactions

A novel approach to the design of dirhodium(II) tetracarboxylates derived from (S)‐amino acid ligands is reported. The approach is founded on tailoring the steric influences of the overall catalyst structure by reducing the local symmetry of the ligand's N‐heterocyclic tether. The application of the new approach has led to the uncovering of [Rh₂(S‐^tertPTTL)₄] as a new member of the dirhodium(II) family with extraordinary selectivity in cyclopropanation reactions. The stereoselectivity of [Rh₂(S‐^tertPTTL)₄] was found to be comparable to that of [Rh₂(S‐PTAD)₄] (up to >99 % ee), with the extra benefit of being more synthetically accessible. Correlations based on X‐ray structures to justify the observed enantioinduction are also discussed.     

Rhodium(II)‐Catalyzed Inter‐ and Intramolecular Cyclopropanations with Diazo Compounds and Phenyliodonium Ylides: Synthesis and Chiral Analysis

Different classes of cyclopropanes derived from Meldrum's acid (=2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione; 4 ), dimethyl malonate ( 5 ), 2‐diazo‐3‐(silyloxy)but‐3‐enoate 16 , 2‐diazo‐3,3,3‐trifluoropropanoate 18 , diazo(triethylsilyl)acetate 24a , and diazo(dimethylphenylsilyl)acetate 24b were prepared via dirhodium(II)‐catalyzed intermolecular cyclopropanation of a set of olefins 3 (Schemes 1 and 4–6). The reactions proceeded with either diazo‐free phenyliodonium ylides or diazo compounds affording the desired cyclopropane derivatives in either racemic or enantiomer‐enriched forms. The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetates 28, 30 , and 33 were carried out in the presence of the chiral dirhodium(II) catalyst [Rh₂{(S)‐nttl)₄}] ( 9 ) in toluene to afford the corresponding cyclopropane derivatives 29, 31 and 34 with up to 37% ee (Scheme 7). An efficient enantioselective chiral separation method based on enantioselective GC and HPLC was developed. The method provides information about the chemical yields of the cyclopropane derivatives, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the inter‐ and intramolecular cyclopropanation reactions and avoids time‐consuming workup procedures.     

Asymmetric Total Synthesis of (−)‐Englerin A through Catalytic Diastereo‐ and Enantioselective Carbonyl Ylide Cycloaddition

An asymmetric total synthesis of the guaiane sesquiterpene (?)‐englerin A, a potent and selective inhibitor of the growth of renal cancer cell lines, was accomplished. The basis of the approach is a highly diastereo‐ and enantioselective carbonyl ylide cycloaddition with an ethyl vinyl ether dipolarophile under catalysis by dirhodium(II) tetrakis[N‐tetrachlorophthaloyl‐(S)‐tert‐leucinate], [Rh₂(S‐TCPTTL)₄], to construct the oxabicyclo[3.2.1]octane framework with concomitant introduction of the oxygen substituent at C9 on the exo‐face. Another notable feature of the synthesis is ruthenium tetraoxide‐catalyzed chemoselective oxidative conversion of C9 ethyl ether to C9 acetate.     

Spiroketal‐Based Phosphorus Ligands for Highly Regioselective Hydroformylation of Terminal and Internal Olefins

A new class of bidentate phosphoramidite ligands, based on a spiroketal backbone, has been developed for the rhodium‐catalyzed hydroformylation reactions. A range of short‐ and long‐chain olefins, were found amenable to the protocol, affording high catalytic activity and excellent regioselectivity for the linear aldehydes. Under the optimized reaction conditions, a turnover number (TON) of up to 2.3×10⁴ and linear to branched ratio (l/b) of up to 174.4 were obtained in the Rh^I‐catalyzed hydroformylation of terminal olefins. Remarkably, the catalysts were also found to be efficient in the isomerization–hydroformylation of some internal olefins, to regioselectively afford the linear aldehydes with TON values of up to 2.0×10⁴ and l/b ratios in the range of 23.4–30.6. X‐ray crystallographic analysis revealed the cis coordination of the ligand in the precatalyst [Rh( 3 d )(acac)], whereas NMR and IR studies on the catalytically active hydride complex [HRh(CO)₂( 3 d )] suggested an eq–eq coordination of the ligand in the species.     

Syntheses and Structures of Four New Tellurium(II) Complexes

The four Te^II complexes, cis‐[TeCl₂{(ⁱPrNH)₂CS}₂] ( 1 ), cis‐[TeCl₂{(ⁱBuNH)₂CS}₂] ( 2 ), trans‐[TeCl₂{(PhNMe)₂CS}₂] ( 3 ), and trans‐[TeCl₂{(Et₂N)₂CS}₂] ( 4 ), have been synthesised and their molecular structures solved by means of X‐ray crystallography. All four complexes are square planar, those with disubstituted thiourea ligands have a cis configuration, those with tetrasubstituted thioureas have a trans configuration. The Te–S bond lengths in 1 and 2 average 2.4994 and 2.5213 Å, respectively. The Te–Cl bonds trans to the Te–S bonds have average lengths of 2.8754 and 2.8334 Å, reflecting the trans influence of the two disubstituted thioureas. In 3 and 4 with identical ligands trans to each other, the average Te–S and Te–Cl bond lengths are 2.6834 and 2.5964 Å, respectively.     

Mechanistic Insights into Cu-Catalyzed Asymmetric Aldol Reactions: Chemical and Spectroscopic Evidence for a Metalloenolate Intermediate

In situ IR spectroscopy and transmetalation experiments confirm a postulated catalytic cycle. The metalloenolate 1 describes the active intermediate in the aldol reaction catalyzed by [CuF₂{(S)-tol-binap}] (see reaction scheme). (S)-tol-binap=(S)-(−)-2,2′-bis(di-p-tolylphosphanyl)-1,1′-binaphthyl.     

Dirhodium(II) Compounds with Bridging Thienylphosphines: Studies on Reversible P,C/P,S Coordination

Monocyclometalated compound [Rh₂{(C₈H₄S)P(C₈H₅S)₂}(CH₃CO₂H)₂(O₂CCH₃)₃] ( 1 a ) and bis‐cyclometalated compound [Rh₂{(C₈H₄S)P(C₈H₅S)₂}₂(CH₃CO₂H)₂(O₂CCH₃)₂] ( 2 a ) have been isolated from the reaction of dirhodium tetraacetate and tris(2‐benzo[b]thienyl)phosphine ( 2 BTP ) using low acidic solutions. By contrast, in pure acetic acid the reaction of Rh₂(O₂CCH₃)₄ with 2 BTP and tris(2‐thienyl)phosphine ( 2 TP ), followed by replacement of the axial acetate ligands by chlorides, led to [Rh₂{(2‐C₈H₅ S )P(2‐C₈H₅S)₂}₂Cl₂(O₂CCH₃)₂] ( 3 b ) and [Rh₂{(2‐C₄H₃ S )P(C₄H₃S)₂}₂Cl₂(O₂CCH₃)₂] ( 5 b ), respectively. These new dirhodium(II) compounds possess equatorial bridging ligands in a phosphorous–sulfur (P,S) coordination mode. The reversible switching between the P,C and P,S bonding mode of the phosphine has been studied in the monocyclometalated [Rh₂{(C₄H₂S)P(C₄H₃S)₂}(CH₃CO₂H)₂(O₂CCH₃)₃] ( 6 a ), which was selectively transformed into compound [Rh₂{(2‐C₄H₃ S )P(C₄H₃S)₂}(CF₃SO₃)(CH₃CO₂H)(O₂CCH₃)₃] ( 7 c ) in triflic acid media. Remarkably, compound 7 c reverts to the starting compound 6 a upon treatment with sodium acetate. Theoretical DFT calculations for both the P,C/P,S rearrangement and the base‐promoted reversion have been performed to explain the experimental findings. Data suggest the P,C/P,S rearrangement occurs by means of a “concerted protonation–demetalation mechanism” followed by η² coordination of the thienyl ring and subsequent isomerization to the S‐η¹‐coordination mode. In the reversion reaction, the base coordinated at the axial position would promote a concerted metalation–deprotonation mechanism.     

Enantio- and diastereoselective hetero-Diels–Alder reactions between 4-methyl-substituted Rawal’s diene and aldehydes catalyzed by chiral dirhodium(II) carboxamidates: catalytic asymmetric synthesis of (−)-cis-aerangis lactone

The first catalytic asymmetric hetero-Diels–Alder (HDA) reaction between 3-tert-butyldimethylsilyloxy-1-dimethylamino-1,3-pentadiene (4-methyl-substituted Rawal’s diene) and aldehydes is described. With 3 mol % of dirhodium(II) tetrakis[N-benzene-fused-phthaloyl-(S)-piperidinonate], Rh₂((S)-BPTPI)₄, the cycloaddition reaction proceeded exclusively in an endo fashion and gave, after a novel sequential treatment with dimethyl acetylenedicarboxylate and acetyl chloride, the corresponding 2,3-cis-disubstituted dihydropyranones with up to 98% ee and perfect diastereoselectivity. The utility of this catalytic protocol was demonstrated by an asymmetric synthesis of the (−)-cis-aerangis lactone.     

Breaking the Mirror: pH‐Controlled Chirality Generation from a meso Ligand to a Racemic Ligand

To study the conversion from a meso form to a racemic form of tetrahydrofurantetracarboxylic acid (H₄L), seven novel coordination polymers were synthesized by the hydrothermal reaction of Zn(NO₃)₂ ? 6 H₂O with (2S,3S,4R,5R)‐H₄L in the presence of 1,10‐phenanthroline (phen), 2,2′‐bipyridine (2,2′‐bpy), or 4,4′‐bipyridine (4,4′‐bpy): [Zn₂{(2S,3S,4R,5R)‐L}(phen)₂(H₂O)] ? 2 H₂O ( 1 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L}(phen)₂(H₂O)₂] ( 2 ), [Zn₂{(2S,3S,4R,5R)‐L}(H₂O)₂] ? H₂O ( 3 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (2,2′‐bpy)₂(H₂O)₂] ? 2 H₂O ( 4 ), [Zn₂ {(2S,3S,4R,5R)‐L}(2,2′‐bpy)(H₂O)] ( 5 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (4,4′‐bpy)₂(H₂O)₂] ( 6 ), and [Zn₂ {(2S,3S,4R,5R)‐L}(4,4′‐bpy)(H₂O)] ? 2 H₂O ( 7 ). These complexes were obtained by control of the pH values of reaction mixtures, with an initial of pH 2.0 for 1 , 2.5 for 2 , 4 , and 6 , and 4.5 for 3 , 5 , and 7 , respectively. The expected configuration conversion has been successfully realized during the formation of 2 , 4 , and 6 , and the enantiomers of L, (2S,3R,4R,5R)‐L and (2S,3S,4S,5R)‐L, are trapped in them, whereas L ligands in the other four complexes retain the original meso form, which indicates that such a conversion is possibly pH controlled. Acid‐catalyzed enol–keto tautomerism has been introduced to explain the mechanism of this conversion. Complex 1 features a simple 1D metal–L chain that is extended into a 3D supramolecular structure by π–π packing interactions between phen ligands and hydrogen bonds. Complex 2 has 2D racemic layers that consist of centrosymmetric bimetallic units, and a final 3D supramolecular framework is formed by the interlinking of these layers through π–π packing interactions of phen. Complex 3 is a 3D metal–organic framework (MOF) involving meso‐L ligands, which can be regarded as (4,6)‐connected nets with vertex symbol (4⁵.6)(4⁷.6⁸). Complexes 4 and 5 contain 2D racemic layers and (6,3)‐honeycomb layers, respectively, both of which are combined into 3D supramolecular structures through π–π packing interactions of 2,2′‐bpy. The structure of complex 6 is a 2D network formed by 4,4′‐bpy bridging 1D tubes, which consist of metal atoms and enantiomers of L. These layers are connected through hydrogen bonds to give the final 3D porous supramolecular framework of 6 . Complex 7 is a 3D MOF with novel (3,4,5)‐connected (6³)(4².6⁴)(4².6⁶.8²) topology. The thermal stability of these compounds was also investigated.