Polyfunctionalized pyrrolidines by Ugi multicomponent reaction followed by palladium-mediated SN2' cyclizations

A 4-component Ugi reaction with a suitable isocyanide, followed by a novel secondary transformation involving a Pd(II)-mediated (R5 = H) or a Pd(0)-mediated (R5 = CO2Me) SN2' cyclization to give highly functionalized N-acyl-2-vinylpyrrolidines, is reported. The overall yields are usually good and in most cases the Pd(0)-catalyzed reaction gave the final product in almost quantitative yield.     

Asymmetric synthesis of a chiral building block for cyclopentanoids: a novel enantioselective synthesis of preclavulone A

A new asymmetric approach to the hydroxylactone (+)-(3aR,4R,6aS)-4-(hydroxymethyl)-3a,4-dihydro-3H-cyclopenta[b]furan-2(6aH)-one (1), a key synthetic building block for cis-1,2-disubstituted five-membered ring derivatives (i.e., isoprostanes, jasmonates, and clavulones), has been described. A remarkable control of the absolute and relative configuration of the three stereocenters was achieved. Thus, the use of the Trost's asymmetric allylic alkylation strategy secured highly enantioenriched (R)-3-(nitromethyl)cyclopent-1-ene (13), which was smoothly converted to (R)-cyclopent-2-enecarboxylic acid (15) in excellent yield and high enantiomeric purity (>98% ee). 6-exo-trig atom-transfer radical cyclizations of ((R)-cyclopent-2-enyl)methyl 2-iodoacetate (12) produced exclusively the desired cis-fused delta-lactone (4aR,7aR)-hexahydro-5-iodocyclopenta[c]pyran-3(1H)-one (11), which was subsequently elaborated to hydroxylactone 1 through a stereocontrolled Pd(II)-mediated lactonization reaction. En route to preclavulone A, a putative elusive intermediate in the biosynthesis of clavulones, the synthetic utility of compound 1 was demonstrated. The key feature in this synthesis was the installation of the lower side chain via the Knochel organozinc sp3-sp C-C coupling protocol.     

Transformation of 3-(Furan-2-yl)-1,3-di(het)arylpropan-1-ones to Prop-2-en-1-ones via Oxidative Furan Dearomatization/2-Ene-1,4,7-triones Cyclization

The approach to 3-(furan-2-yl)-1,3-di(het)arylprop-2-en-1-ones based on the oxidative dearomatization of 3-(furan-2-yl)-1,3-di(het)arylpropan-1-ones followed by an unusual cyclization of the formed di(het)aryl-substituted 2-ene-1,4,7-triones has been developed. The cyclization step is related to the Paal–Knorr synthesis, but the furan ring formation is accompanied in this case by a formal shift of the double bond through the formation of a fully conjugated 4,7-hydroxy-2,4,6-trien-1-one system or its surrogate.     

Palladium acetate-catalyzed cyclization reaction of 2,3-allenoic acids in the presence of simple allenes: an efficient synthesis of 4-(1'-bromoalk-2'(Z)-en-2'-yl)furan-2(5H)-one derivatives and the synthetic application

We have realized a cyclization reaction of 2,3-allenoic acids 1 in the presence of simple alkyl- or aryl-substituted allenes 3. In this reaction, the cyclic oxypalladation of 2,3-allenoic acid with Pd(II) would afford the furanonyl palladium intermediate 2, which could be trapped by the simple allene to afford a pi-allylic intermediate anti-9. This intermediate anti-9 could be nucleophilically attacked by Br- to yield 4-(1'-bromoalk-2'(Z)-en-2'-yl)furan-2(5H)-one derivatives Z-5 and Pd(0). The in-situ formed Pd(0) was efficiently converted to the catalytically active Pd(II) species by benzoquinone in HOAc. The functional groups, such as malonate, acetoxyl, and phthalic amide in allene 3, are tolerable under the current conditions. High efficiency of chirality transfer was observed when optically active 2,3-allenoic acids were used, which reveals that the formation of the intermediates 2 was a highly stereoselective anti-oxypalladation process. The highly selective formation of Z-isomer may be explained by face-selective coordination of allene 3 with the palladium atom in intermediate 2: the palladium atom coordinates to the terminal C=C double bond of allene 3 from the face opposite to the substituent group to avoid the steric congestion. The products Z-5 could be further elaborated via the S(N)2 nucleophilic substitution with amine or sodium benzenesulfinate, the reduction of the C-Br bond by NaBH(4), and the CuBr.SMe(2)-catalyzed S(N)2'-substitution with CH(3)MgBr.     

Palladium(II) acetate mediated oxidative cyclization of omega-unsaturated alpha-cyano ketones. A facile methylenecyclopentane annulation process

A highly efficient methylenecyclopentane annulation process has been developed based on the Pd(II)-mediated oxidative cyclization of omega-unsaturated alpha-cyano ketones, readily accessed via the Michael addition of 3-butenylmagnesium bromide with 2-cyano-2-cycloalkenones.     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

Hydrogenolysis of palladium(II) hydroxide, phenoxide, and alkoxide complexes

A series of pincer ((tBu)PCP)Pd(II)-OR complexes ((tBu)PCP = 2,6-bis(CH(2)P(t)Bu(2))C(6)H(3), R = H, CH(3), C(6)H(5), CH(2)C(CH(3))(3), CH(2)CH(2)F, CH(2)CHF(2), CH(2)CF(3)) were synthesized to explore the generality of hydrogenolysis reactions of palladium-oxygen bonds. Hydrogenolysis of the Pd hydroxide complex to generate the Pd hydride complex and water was shown to be inhibited by formation of a water-bridged, hydrogen-bonded Pd(II) hydroxide dimer. The Pd alkoxide and aryloxide complexes exhibited more diverse reactivity. Depending on the characteristics of the -OR ligand (steric bulk, electron-donating ability, and/or the presence of β-hydrogen atoms), hydrogenolysis was complicated by hydrolysis by adventitious water, a lack of reactivity with hydrogen, or a competing dissociative β-hydride abstraction reaction pathway. Full selectivity for hydrogenolysis was observed with the partially fluorinated Pd(II) 2-fluoroethoxide complex. The wide range of Pd-OR substrates examined helps to clarify the variety of reaction pathways available to late-transition-metal alkoxides as well as the conditions necessary to tune the reactivity to hydrogenolysis, hydrolysis, or dissociative β-hydride abstraction.     

Alkene metatheses in transition metal coordination spheres: dimacrocyclizations that join trans positions of square-planar platinum complexes to give topologically novel diphosphine ligands

The alkene-containing phosphines PPh((CH2)(n)CH=CH2)2)2 are prepared from PPhH(2), n-BuLi, and the corresponding bromoalkenes (1:2:2), and combined with the platinum tetrahydrothiophene complex [Pt(mu-Cl)(C(6)F(5))(S(CH2CH2(-))2)]2 to give the square-planar adducts trans-(Cl)(C(6)F(5))Pt(PPh((CH2)(n)CH=CH2)2)2 (11, 93-73%; n=a, 2; b, 3; c, 4; d, 5; e, 6; f, 8). Ring-closing metatheses with Grubbs' catalyst (2) are studied. With, two isomers of trans-(Cl)(C6F5)[formula: see text](14)Ph)(15e) are isolated after hydrogenation. Both form via dimacrocyclization between the trans-phosphine ligands, but differ in the dispositions of the PPh rings (syn, 31%; anti, 7%). The alternative intraligand metathesis product trans-(Cl)(C6F5)[formula: see text](14)Ph)2 (16e) is independently prepared by (i) protecting 4e as a borane adduct, H(3)B.PPh((CH(2))(6)CH=CH2)2, (ii) cyclization with 2 and hydrogenation to give H(3)B[formula: see text] (14), (iii) deprotection and reaction with 12. The sample derived from 11e contains < or = 2% 16e; mass spectra suggest that the other products are dimers or oligomers. The structures of syn-15e, anti-15e and 16e are verified crystallographically, and the macrocycle conformations analyzed. As expected from the (CH(2))(n) segment length, 11a undergoes intraligand metathesis to give (Z,Z)-trans-(Cl)(C6F5)Pt[formula: see text]CH2)2)2 (86%), as confirmed by a crystal structure of the hydrogenation product. Although 11b does not yield tractable products, 11c gives syn-(E,E)-trans-(Cl)(C6F5[formula:see text](21%). This structure, and that of the hydrogenation product (syn-15c; 95%), are verified crystallographically. Analogous sequences with 11d,f give syn-15d (5 and 14% overall).     

Pd(CH3CN)2Cl2-catalyzed oxidative heterodimerization reaction of 2,3-allenamides and 1,2-allenyl ketones: an efficient synthesis of 4-(furan-3'-yl)-2(5H)-furanimines

The Pd(II)-catalyzed oxidative heterodimerization reaction of 2,3-allenamides and 1,2-allenyl ketones was studied. It provides an efficient route for the synthesis of the polysubstituted 4-(furan-3'-yl)-2(5H)-furanimines, which are not readily available from the known methods. Due to the application of benzoquinone, the loadings of both the palladium catalyst and ketone have been greatly reduced for the oxidative heterodimerization of 2,3-allenamides and 1,2-allenyl ketones in acetic acid.     

Structural characterization of four members of the electron-transfer series [PdII(L)2)2]n (L = o-Iminophenolate derivative; n = 2-, 1-, 0, 1+, 2+). ligand mixed valency in the monocation and monoanion with S = (1)/(2) ground states

The reaction of the ligand 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol, H(2)((1)L(IP)), and PdCl(2) (2:1) in the presence of air and excess NEt(3) in CH(2)Cl(2) produced blue-green crystals of diamagnetic [Pd(II)((1)L(ISQ))(2)] (1), where ((1)L(ISQ))(*)(-) represents the o-iminobenzosemiquinonate(1-) pi radical anion of the aromatic ((1)L(IP))(2-) dianion. The diamagnetic complex 1 was chemically oxidized with 1 equiv of Ag(BF(4)), affording red-brown crystals of paramagnetic (S = (1)/(2)) [Pd(II)((1)L(ISQ))((1)L(IBQ))](BF(4)) (2), and one-electron reduction with cobaltocene yielded paramagnetic (S = (1)/(2)) green crystals of [Cp(2)Co][Pd(II)((1)L(ISQ))((1)L(IP))] (3); ((1)L(IBQ))(0) represents the neutral, diamagnetic quinone form. Complex 1 was oxidized with 2 equiv of [NO]BF(4), affording green crystals of diamagnetic [Pd(II)((1)L(IBQ))(2)](3)(BF(4))(4){(BF(4))(2)H}(2).4CH(2)Cl(2) (5). Oxidation of [Ni(II)((1)L(ISQ))(2)] (S = 0) in CH(2)Cl(2) solution with 2 equiv of Ag(ClO(4)) generated crystals of [Ni(II)((1)L(IBQ))(2)(ClO(4))(2)].2CH(2)Cl(2) (6) with an S = 1 ground state. Complexes 1-5 constitute a five-membered complete electron-transfer series, [Pd((1)L)(2)](n) (n = 2-, 1-, 0, 1+, 2+), where only species 4, namely, diamagnetic [Pd(II)((1)L(IP))(2)](2-), has not been isolated; they are interrelated by four reversible one-electron-transfer waves in the cyclic voltammogram. Complexes 1, 2, 3, 5, and 6 have been characterized by X-ray crystallography at 100 K, which establishes that the redox processes are ligand centered. Species 2 and 3 exhibit ligand mixed valency: [Pd(II)((1)L(ISQ))((1)L(IBQ))](+) has localized ((1)L(IBQ))(0) and ((1)L(ISQ))(*)(-) ligands in the solid state, whereas in [Pd(II)((1)L(ISQ))((1)L(IP))](-) the excess electron is delocalized over both ligands in the solid-state structure of 3. Electronic and electron spin resonance spectra are reported, and the electronic structures of all members of this electron-transfer series are established.     

Novel PdII-mediated cascade carboxylative annulation to construct benzo[b]furan-3-carboxylic acids

[reaction: see text] Benzo[b]furan-3-carboxylic acid (2) was generated from 1 by forming three new bonds in one step via a Pd(II)-mediated cascade carboxylative annulation. The proposed mechanism was supported by the observation of an unusual acetylation of 1 as a side reaction together with an (18)O-labeling study.     

吡唑并三嗪[1,5-a][1,3,5]-4(3H)-酮类衍生物的合成

设计并实现了以具有脒代吡唑结构的中间体与三聚光气在低温下进行分子内环合得到吡唑并三嗪[1,5-a][1,3,5]-4(3H)-酮衍生物(9a~9c)的新方法。1H NMR,IR,MS和元素分析表征证明9a~9c为新化合物。     

Chiral bisphosphinite metalloligands derived from a P-chiral secondary phosphine oxide

Interaction of PdCl(2)(MeCN)(2) with 2 equiv of (S(P))-(t)BuPhP(O)H (1H) followed by treatment with Et(3)N gave [Pd((1)(2)H)](2)(micro-Cl)(2) (2). Reaction of 2 with Na[S(2)CNEt(2)] or K[N(PPh(2)S)(2)] afforded Pd[(1)(2)H](S(2)CNEt(2)) (3) or Pd[(1)(2)H)[N(PPh(2)S)(2)] (4), respectively. Treatment of 3 with V(O)(acac)(2) (acac = acetylacetonate) and CuSO(4) in the presence of Et(3)N afforded bimetallic complexes V(O)[Pd(1)(2)(S(2)CNEt(2))](2) (5) or Cu[Pd(1)(2)(S(2)CNEt(2))](2) (6), respectively. X-ray crystallography established the S(P) configuration for the phosphinous acid ligands in 3 and 6, indicating that 1H binds to Pd(II) with retention of configuration at phosphorus. The geometry around Cu in 6 is approximately square planar with the average Cu-O distance of 1.915(3) A. Treatment of 2 with HBF(4) gave the BF(2)-capped compound [Pd((1)(2)BF(2))](2)(micro-Cl)(2) (7). The solid-state structure of 7 containing a PdP(2)O(2)B metallacycle has been determined. Chloride abstraction of 7 with AgBF(4) in acetone/water afforded the aqua compound [Pd((1)(2)BF(2))(H(2)O)(2)][BF(4)] (8) that reacted with [NH(4)](2)[WS(4)] to give [Pd((1)(2)BF(2))(2)](2)[micro-WS(4)] (9). The average Pd-S and W-S distances in 9 are 2.385(3) and 2.189(3) A, respectively. Treatment of [(eta(6)-p-cymene)RuCl(2)](2) with 1H afforded the phosphinous acid adduct (eta(6)-p-cymene)RuCl(2)(1H) (10). Reduction of [CpRuCl(2)](x)() (Cp = eta(5)-C(5)Me(5)) with Zn followed by treatment with 1H resulted in the formation of the Zn(II) phosphinate complex [(CpRu(eta(6)-C(6)H(5)))(t)BuPO(2))](2)(ZnCl(2))(2) (11) that contains a Zn(2)O(4)P(2) eight-membered ring.     

Palladium(II) acetate mediated oxidative cyclization of ω-unsaturated α-cyano ketones for facile construction of methylenecyclohexane ring system

A highly efficient annulative approach towards the construction of the structurally attractive methylenecyclohexane ring was developed through a convenient 1,4-addition of 4-pentenylmagnesium bromide to 2-cyano-2-cycloalkenones followed by a Pd(II)-mediated oxidative cyclization of the resulting ω-unsaturated α-cyano ketones. Based on this newly developed protocol, polycyclic adducts bearing various ring sizes and substitutions can be prepared in moderate to high yields.     

Regiocontrolled intramolecular cyclizations of carboxylic acids to carbon-carbon triple bonds promoted by acid or base catalyst

We systematically investigated, for the first time, the relationship between regioselectivity and acid/base effects in the cyclization reactions between carboxylic acids and carbon-carbon triple bonds. We found novel acid- and base-promoted cyclizations to selectively give isocoumarin or pyran-2(2H)-one and phthalide or furan-2(5H)-one skeletons, respectively, and established a catalytic version of regioselective heterocyclic ring synthesis. Density functional theory calculations and application to a short route to thunberginol A were also described. [reaction: see text].     

Synthesis of 3-(2-Oxo-2,3-dihydrobenzo[<Emphasis Type="Italic">b</Emphasis>]furan-3-ylidenehydrazono)-2,3-dihydrobenzo[<Emphasis Type="Italic">b</Emphasis>]furan-2-one

Reactions of benzophenone and fluoren-9-one hydrazones with (2-hydroxyphenyl)oxoacetic acid gave [carboxy(2-hydroxyphenyl)methylidenehydrazono](2-hydroxyphenyl)acetic acid which underwent intramolecular cyclization with formation of 3-(2-oxo-2,3-dihydrobenzo[bfuran-3-ylidenehydrazono)-2,3-dihydrobenzo[b]furan-2-one. The symmetric azine was also obtained by reactions of (2-hydroxyphenyl)oxoacetic acid with triphenylphosphoranylidenehydrazones derived from benzophenones, fluoren-9-one, and 1-methyl-2,3-dihydro-1H-indole-2,3-dione.     

Synthesis of spirocyclic azacycles from the cyclization of furan tethered N-acyliminium ions

The protic and Lewis acid promoted cyclization reactions of tethered furan-4,5-dihydroxypiperid-2-ones, furan-4,5-diacetoxypiperid-2-ones and furan-3,4-diacetoxypyrrolid-2-ones, via their corresponding N-acyliminium ion intermediates, have been studied. In the case of the furan-4,5-dihydroxypiperid-2-one 2a and its diacetate derivative 2b, macrocyclic products were formed from an initial intermolecular reaction between 2a or 2b, via the nucleophilic C5 furan carbon, and their corresponding N-acyliminium ion intermediates. When the furan C5 position of 2b was blocked by substitution with bromine then TFA or Sc(OTf)₃ catalysed cyclization reactions gave a spirotricyclic product (a 5-6-6-tricycle) in a highly diastereoselective manner. Cyclization of the analogous C5-Br-furan-pyrrolidone 29 with TFA resulted in a related spirotricyclic (a 5-6-5 tricycle) product. Attempts to prepare an analogous azepine system, a 5-7-5 tricycle, were not successful. Cyclization reactions of the C5-PhS-furan- or C5-phenylsulfonyl-pyrrolidone analogues of 29 with TFA were also not successful.     

Palladium-catalyzed aerobic intermolecular cyclization of acrylic acid with 1-octene to afford α-methylene-γ-butyrolactones: the remarkable effect of continuous water removal from the reaction mixture and analysis of the reaction by kinetic, ESI-MS, and XAFS measurements

Further study of our aerobic intermolecular cyclization of acrylic acid with 1-octene to afford α-methylene-γ-butyrolactones, catalyzed by the Pd(OCOCF(3))(2)/Cu(OAc)(2)?H(2)O system, has clarified that the accumulation of water generated from oxygen during the reaction causes deactivation of the Cu cocatalyst. This prevents regeneration of the active Pd catalyst and, thus, has a harmful influence on the progress of the cyclization. As a result, both the substrate conversion and product yield are efficiently improved by continuous removal of water from the reaction mixture. Detailed analysis of the kinetic and spectroscopic measurements performed under the condition of continuous water removal demonstrates that the cyclization proceeds in four steps: 1)?equilibrium coordination of 1-octene to the Pd acrylate species, 2)?Markovnikov-type acryloxy palladation of 1-octene (1,2-addition), 3)?intramolecular carbopalladation, and 4)?β-hydride elimination. Byproduct 2-acryloxy-1-octene is formed by β-hydride elimination after step 2). These cyclization steps fit the Michaelis-Menten equation well and β-hydride elimination is considered to be a rate-limiting step in the formation of the products. Spectroscopic data agree sufficiently with the existence of the intermediates bearing acrylate (Pd-O bond), η(3)-C(8)H(15) (Pd-C bond), or C(11)H(19)O(2) (Pd-C bond) moieties on the Pd center as the resting-state compounds. Furthermore, not only Cu(II), but also Cu(I), species are observed during the reaction time of 2-8?h when the reaction proceeds efficiently. This result suggests that the Cu(II) species is partially reduced to the Cu(I) species when the active Pd catalytic species are regenerated.     

Autocatalytic oxidative addition of PhBr to Pd(PtBu3)2 via Pd(PtBu3)2(H)(Br)

We report that oxidative addition of bromobenzene to Pd(PtBu3)2 occurs by an unusual autocatalytic mechanism. Studies on the effect of various additives showed that the degree of rate acceleration followed the trend: (PtBu3)Pd(Ph)(Br) approximately (HPtBu3)Br < [(PtBu3)Pd(mu-Br)]2 < (PtBu3)2Pd(H)(Br). Studies on the reactions of Pd(PtBu3)2 in the presence of (PtBu3)2Pd(H)(Br) showed that the concentration of (PtBu3)2Pd(H)(Br) decreased only after the Pd(0) complex had been consumed. These data indicated that the catalyst in this process is (PtBu3)2Pd(H)(Br). Thermal decomposition of the three-coordinate oxidative addition product (PtBu3)Pd(Ar)(Br) during the reaction of Pd(PtBu3)2 and bromoarenes ultimately leads to formation of (PtBu3)2Pd(H)(Br). Parallel reactions of bromobenzene with (PtBu3)2Pd(H)(Br) and Pd(PtBu3)2 showed that the bromoarenes reacted considerably faster with the Pd(II) species than with the Pd(0) species. We therefore propose a catalytic cycle for oxidative addition in which PBut3.HBr reacts with the Pd(0) species to form (PtBu3)2Pd(H)(Br), and (PtBu3)2Pd(H)(Br) reacts with the bromoarene, possibly though the anionic species [HPtBu3+][(PtBu3)Pd(Br)-], to form [Pd(PtBu3)(Ar)(Br)].     

Palladium-catalyzed asymmetric phosphination. Scope, mechanism, and origin of enantioselectivity

Asymmetric cross-coupling of aryl iodides (ArI) with secondary arylphosphines (PHMe(Ar'), Ar' = (2,4,6)-R3C6H2; R = i-Pr (Is), Me (Mes), Ph (Phes)) in the presence of the base NaOSiMe3 and a chiral Pd catalyst precursor, such as Pd((R,R)-Me-Duphos)(trans-stilbene), gave the tertiary phosphines PMe(Ar')(Ar) in enantioenriched form. Sterically demanding secondary phosphine substituents (Ar') and aryl iodides with electron-donating para substituents resulted in the highest enantiomeric excess, up to 88%. Phosphination of ortho-substituted aryl iodides required a Pd(Et-FerroTANE) catalyst but gave low enantioselectivity. Observations during catalysis and stoichiometric studies of the individual steps suggested a mechanism for the cross-coupling of PhI and PHMe(Is) (1) initiated by oxidative addition to Pd(0) yielding Pd((R,R)-Me-Duphos)(Ph)(I) (3). Reversible displacement of iodide by PHMe(Is) gave the cation [Pd((R,R)-Me-Duphos)(Ph)(PHMe(Is))][I] (4), which was isolated as the triflate salt and crystallographically characterized. Deprotonation of 4-OTf with NaOSiMe3 gave the phosphido complex Pd((R,R)-Me-Duphos)(Ph)(PMeIs) (5); an equilibrium between its diastereomers was observed by low-temperature NMR spectroscopy. Reductive elimination of 5 yielded different products depending on the conditions. In the absence of a trap, the unstable three-coordinate phosphine complex Pd((R,R)-Me-Duphos)(PMeIs(Ph)) (6) was formed. Decomposition of 5 in the presence of PhI gave PMeIs(Ph) (2) and regenerated 3, while trapping with phosphine 1 during catalysis gave Pd((R,R)-Me-Duphos)(PHMe(Is))2 (7), which reacted with PhI to give 3. Deprotonation of 1:1 or 1.4:1 mixtures of cations 4-OTf gave the same 6:1 ratio of enantiomers of PMeIs(Ph) (2), suggesting that the rate of P inversion in 5 was greater than or equal to the rate of reductive elimination. Kinetic studies of the first-order reductive elimination of 5 were consistent with a Curtin-Hammett-Winstein-Holness (CHWH) scheme, in which pyramidal inversion at the phosphido ligand was much faster than P-C bond formation. The absolute configuration of the phosphine (SP)-PMeIs(p-MeOC6H4) was determined crystallographically; NMR studies and comparison to the stable complex 5-Pt were consistent with an RP-phosphido ligand in the major diastereomer of the intermediate Pd((R,R)-Me-Duphos)(Ph)(PMeIs) (5). Therefore, the favored enantiomer of phosphine 2 appeared to be formed from the major diastereomer of phosphido intermediate 5, although the minor intermediate diastereomer underwent P-C bond formation about three times more rapidly. The effects of the diphosphine ligand, the phosphido substituents, and the aryl group on the ratio of diastereomers of the phosphido intermediates Pd(diphos*)(Ar)(PMeAr'), their rates of reductive elimination, and the formation of three-coordinate complexes were probed by low-temperature 31P NMR spectroscopy; the results were also consistent with the CHWH scheme.