Reprinted I'rom The Journal of Organic ('hemistry, 1981,'16, 2861. Copyright O 1981by the American Chemical Society and reprinted by permissionof the copyright owner
Synthesis of Functional Chelating Diphosphines Containing the Bis[2-(diphenylphosphino)ethyl]aminoMoiety and the Use of These Materials in the Preparation of Water-Soluble Diphosphine Complexesof Transition Metalsr
Ralph G. Nuzzo, Sharon L. Haynie, Michael E. Wilson, and GeorgeM. Whitesides*
Department of Chemistry, MassachusettsInstitute of Technology,Carnbridge, Massachusetts 02139
ReceiuedMarch 19. 1981
Acylation of bis[2-(diphenylphosphino)ethyl]amine provides a flexible synthesis of functionalized chelating diphosphines. This t.uitiott off"rs a route to diphosphine complexes of transition metals having a wide r?n-ge of structures and physical properties and especiallyto water-soluble complexes. The aqueoussolubility of the free ligands and of ttre compleres prepared from them depend on the ligand, on the metal, and on other materials (especially surfactants) present in the solution. We describe typical preparations of ligands and outline the properties of their complexes with certain transition metals.
Homogeneous catalysis and asymmetric synthesis in- functionalized, water-soluble,chelating diphosphines and creasingly require complex organic structures incorporating presented examples of applications of these materials. ligands capable of coordinating a transition-metal center. This paper provides experimental proceduresfor these In earlier papers,2-awe described a flexible synthesisof synthesesand outlines factors affecting the properties of the resulting materials in aqueous solutions.
(1) Supported by the National Science Foundation (Grants Results and Discussion 77LL282CHE and8012722-CHE). R.G.N. held a predoctoral traineeship from the National Cancer Institute (CA 09112CT) and S.L.H. an HEW All synthesesare basedon bisl2-(diphenylphosphino)- predoctoral fellowship. ethyllamine 1 (SchemeI).5 This compound, isolated as (2) Wilson, M. E.; Whitesides,G. M. Arn. Chem. Soc.1978,100, "/. air-stable hydrochloride' can be acylated at 306-307. a crystalline, (3) Wilson, M.E.; Nuzzo,R. G.;Whitesides,G. M. J. Am. Chem. Soc. 1978, 100,2269-2270. (4) Nuzzo, R. G.; Feitler, D.; Whitesides,G. M. J. Am. Chem. Soc. (5) Compound 1 was first prepared by: Sacconi, L.; Marassi, R. J. 1979, 101,3683-3685. Chem. Soc. A 1968,2997-3002. 2862 J. Org.Chem., Vol. 46, No. 14, 1981 \r.rz-zr,€t al
Scheme I. Preparation of Bis[2-(diphenylphosphino )ethyl]amine and Derivatives
-.- ,.4", wl l) 2 Ph2Pfl .Apph^ cl'' H^N'z''a--rct - (cH--[coKJHF* t' t.tr. ,rn. 2) HCI
r I o -4=4 I ll l0 I \-z:( 'b I o-- i I 4 i
o I /-1,'PPhz I /1pp,""2 !-7.=y/(J \ n AY';r1 \-//PPhz or)',) \-''PPhz oiY/1po- . -h? .\ 4"", - ^-/( N' -" 'r--,rPPh, l o O 5 5, i I , Nuc, Nuc: I t
O0 0 'oF\ xo$'r-^.tr,,- n'1PPh. o 'PPh2 u,,\1\2 . /PPh, tlrcfA _,.r(- 0 1----'PPh'
Y
nitrogen without competingreaction at phosphorus. The groups.These groups can be designedto conferthe desired ability to functionalizenitrogen selectively,inthe presence physicalpropertres to the final complex. of the phosphinecenters is the basisfor a method for the An alternativestrategy, direct ac1'lation of 1 te.g..I + incorporationof I into complex organicstructures. 7) is also suc'c'essful.Although this procedureappears The reactivity of I toward acid chlorides,anhl'drides, simpler.in practicewe havefound it to be lessuseful than isocyanates,alkyl chlorocarbonates.and .\'-hvdroxl'- I - 5 - 8 or I -. 6 -* 9 as a method for generating succinimide (NHS) active estersis that erpected for a functionalized (especiallywater soluble) diphosphines. stericallyhindered, secondary amine. Theserea('tions go The number of readily availablereactive species of the trpe to completionat ambient temperatures(the time necessarv representedby 4 (that is, specieswhich react selectivell' for reactiondepends both on the couplinggroup empkrl'ed with nitrogen in the presenceof phosphorusand w'hich and on the nature of additionalbases present in solution; introducehighly polar groups)is small. Bv contrast.2 is see Experimental Section). Little or no competing re- commerciallyavailable and inexpensive,and 5 react-sn'ith activity is observedfor the phosphinegroups. Onlv in the a wide range of amines. In applicationsin n'hich rl'ater casesof materials capableof reactionsother than acylation solubility is not an important objective.hon'ever. direct do competing reactionsbecome important: specialcare acylation can provide a convenientand useful methodolog'u' must be exercisedin usingthese coupling agenLs. Acryloyl (vide infra). chloride can be used to acylate I under the conditions Table I lists the substancesprepared. the coupling describedbelow. All attempts to acylate I with maleic agentsused in their preparation,and the vields in which anhydride gaveonly air-sensitive,red gums: although some they wereobt.ained. The purification and characterization amide formation is apparent in the IR spectra of the re- of these complexesproved difficult. Manl' have surfactant action mixtures, we have been unable to isolate a useful properties;their polar functionalities are hydrated or derivative of I from these mixtures. Soft electrophiles solvated to varying extents; they are noncrystaliine. (sulfonyl chlorides,cyanogen bromide, phosphoryi halides) Characterizationoften was basedprimarily on IR and 31P also seem not to demonstrate the selectivity toward ni- and lH NMR spectroscopiesand on the physical properties trogen required to achieve useful functionalization. (water solubility, abilit5,'to complexmetals) of the com- The most useful synthetic strategy to emergefrom this pounds. Only compounds10, 12, 13, 15, 17,2l,and 22 were work used a diacylating reagent [trimellitic anhydride acid isolated in a form sufficiently pure to give acceptableel- chloride (2) or tricarballylic anhydride acid chloride (3)l emental analyses.Analytical data for others are included to couple I to another amine-containing group which in the ExperimentalSection, as an aid in judging purity. conferredthe physical properties required. Thus, for ex- Yields given in parenthesesin Table I are for crude com- ample, reaction of 1 with 2 proceedscleanly at the more pounds and are upper limits. reactive acid chloride site and generates5. The effect of The proton NMR spectra of a number of the water- this transformation is to convert 1 (in which functionali- solublederivatives (17-20) in aqueoussolution show broad, zation is based on the difference between the nucleo- complexresonances. suggesting micelle formation, although philicity of the nitrogen and phosphoruscenters) to 5 (in the presenceof aggregatedstructures was not rigorously which functionalization can be basedon the electrophilic established.The 31PNMR spectraof the free ligandsare anhydride group, without competition from the phosphine usuallycharacterized by'two linescentered at -1.5 ppm. centers). Compound 5 (and the analogous6) is not isolated Control experimentsdemonstrated that the splitting occ\us but is allowed to react directly with other nucleophilic on acylation;we a^ssumethat it reflects slow rotation about Functional Chelating Diphosphines J. Org.Chem., Vol. 46, No. 14, 1981 2863
Table I. Functionalized Diphosphines from L having 7 as a ligand.6'7 Of the severalmetals examined - lNP, N(CHrCHrPPhr)rl in this study, the cationic rhodium complexeswere the reacting yield,o most soltrblein water. compd group % The aqueoussolubility of the free ligands seemsto follow expectedtrends. The doubly chargedspecies 17, 18,and o o ,/"-1 20 are much more soluble than singly chargedmaterials (Yn" Ip \y'so.Ho \.^,Ss^ such as 7, 16, and 19. The neutral polyethyleneglycol o sy'steml1 shows increasingsolubility with increasing '(\' RCONHS = 11O molecularweight: at n 110the material appearsto be ( s)--.-,-.r,/(Np. completelysoluble. In this sameseries similar changes I rverenoted in the solubility of 11.PtCl2complexes. c Hr( ocHzcH 2)n O C NP2 ROCOCI n. 2,6, ltO HomogeneousCatalysis by Cationic Rhodium Com- 'f plexes. he Rh(I) complexesof severalof theseligands Ph NHC NPz RNCO 93 have been shown to act as effective homogeneoushydro- J genation c'atalystsin aqueoussolution for a range of r3 .ltt.o, 4coHe, Anhydr ith w'ater-solublesubstrates.a The data presentedbelow ex-
HPlP. pand Llponearlier observations.a t4 o\r?o In general,the most solublecomplexes acted as the best Anhy dri dc (e.g., 4' OMe'n catalvsts. Catalyststhat precipitated from solution l6.Rh(l )) saveunderstandably low rates of hydrogenation t5 c H3coN P2 RCOC rr.ithtr-acetamidoacrylic acid (turnover number = TN < i mol of olefin reduced/mol of rhodium complex/h).
16 xo.c'.r/\ne. A nhtd rr da Solubilitv is, however,not the only requirementfor high ac'tivitl'sincell.Rh(I) (a = 16, 110)was a poor catalyst O HOt\,--\y Np_ despiteits reasonablyhigh solubility in water. The com- t7 lz5 aac* pler 7.Rh(I) was sparinglysoluble and had low activity. o ro oI1\7irc, Since7 is extremelysoluble, we infer that coordinationof 18 *0.t, 3 -aTf/ _--,-] the sulfonicacid group to rhodium resultsin this decrease 0- in ,solubilityand activity.8 In our hands,rhodium com- xoir, o rs 6 plexesof l7 and 18 formed the catalystshaving the highest /Yf--Ant lo For reasons, \NHCO(CHOH)4CH2OH activitl'. several we believe that the best material for most applications in homogeneoushydro- 0 no{--\ genationis 17.Rh(I). First, unlike most of theseligands, ?o Noo.s 6 J ;"i'lr,/'-\./^Npz -t - purified. \ 7, 17 is highly crystallineand is easily Second,the o protonated form of the acid is soluble in a wide range of o_0 /-\ il ?t Hf Rcocl organic solvents,a feature attractive for catalyst prepa- il\ /)-cNP2 42 o- ration. Dissolution in water is easily accomplished by L1-\ I transferring the catalyst preparation in a water-miscible P2Nc{'>cNP2 w organic solvent such as acetone,under argon, into the reactionmedia. In this manner,the number of manipu- ?3 Ph.P (CH.CH.O) RCi rMe lations necessaryto prepare the catalyst can be minimized. Third, the synthesisof 17 is simple and can be easily
24 -r'-\(Npz Rcocl ,9a 1 carried out on practical scales:routine preparationsgave o? more than 10 g of purified material in nearly quantitative '-i.?l yield. Fourth, hydrogenationrates with 17.Rh(I) 25 o (-\r b e. are the -t:t-'^ 'af NH(cH2)r'cH3 ,.*i highest observedfor any derivative of 1: for example,TNs U > 275h't (Pn, = 32 psi; -4000 turnoversof Rh(I), 100To o Yields given in parentheses are for crude compouncls reduction) were found with a-acetamidoacrylicacid as a and are upper limits. substrate. An interesting effect is observedwhen hydrogenations 31P the amide bond. Examination of the NMR data also using 16.Rh(I),a poor catalyst,are carried out in aqueous showedthat tlpical preparationsof ligandscontained (5% solutions containing 0.1% by weight sodium dodecyl contamination by phosphine oxides. The phy'sicalprop- sulfate. Under these conditions, useful rates (TN = 120 erties of most of these compoundsmade purification dif- h-l for a-acetamidoacrylic acid) were observed. This ficult, and great care was required to prevent oxidation catalyst system was also found to be extremely stable, during manipulation or in syntheses.For similar reasons, maintaining most of its catalytic activity even in the all reagentswere purified carefully prior to use. In most presenceof low concentrationsof substrate. At the com- instances,impurities do not affect the performanceof these pletion of the reduction (total turnover number of Rh(I) materials as ligands for transition metals. >4000, 100% reduction) bright yellow and completely Solubility of Metal Complexes and Ligands. As homogeneoussolutions were obtained. Thus, it appears might be expected,the nature of the metal coordinated that 16.Rh(I) is incorporated into SDS micellesand that to a particular ligand strongly influencesthe solubility of the final complex. For example, 1l (n = 16) forms a stable though sparingly soluble platinum(Il) dichloride complex. (6) An exception was found for ll.NiCl2 (n = 110). This material forms stable red solutions in water. The cause of this effect is not un- When coordinatedto a rhodium(I) norbornadienecation, derstood. 1l.Rh(Nbd)*, a much more solublematerial is obtained. (7) Similar behavior was also observed with both NiBr2 and NiI2 This sameligand in the red-browncomplex 11.NiCl2 de- complexesof a number of the ligands. (8) composesto an insoluble white Related effects have been observed with sulfonated triphenyl- w€x on contact with water. phosphinecomplexes of Rh(I). See: Borowski,A. F.; Cole-Hamilton,D. Similar results were also observedwith nickel complexes J.; Wilkinson, G. Nouu. J. Chim. 1978,2,137-144. 2864 J. Org. Chem.,Vol. 46, No. 14, 1981 Nuzzo et al. this incorporation somehow stabilizesthe complex.e THF and diethyl ether were distilled from sodium benzophenone Rhodium complexesof 10 and 21, themselvesinsoluble dianion under argon. Methylene chloride and methanol (analytical in water, dissolveeasily in aqueoussolutions containing grade) were used without further purification. Taurine, bis(2- stoichiometric amounts of avidin3 and carbonic anhy- chloroethyl)amine hydrochloride, tricarballylic acid, and trimellitic anhydride acid chloride were obtained from Aldrich. o-Sulfo- drase,l0respectively. In these instances,solution reflects benzoicanhydride was obtained from Eastman. o-Gluconic acid protein. specific binding of the diphosphine to the d-lactonewas obtained from Sigma. A generoussample of o-biotin The catalytic activities of the rhodium complexesof 17 was a gift of the Hoffmann-La Roche Co. Polyethyleneglycol and 25 are dramatically influenced bV the presenceof monomethylethers (mol wt -500, 750,5000)were purchasedfrom a-chymotrypsin and bovine serum albumin in solution. Polyscience.Gantrez AN-119, a copollmer of methyl vinyl ether Although the nature of the interaction of these substrates and maleic anhydride, was purchasedby GAF. Pyridine was with these proteins has not been established,llpreliminary distilled from calcium hydride under argon. Triethylamine was studies indicate that albumin may influence the substrate purified by treatment with benzoicanhydride followed by dis- specificity of the rhodium catalyst. The conjugate of tillation. Ethylenediaminewas distilled under argon. Reagent grade (Eastman) purifi- 1O.Rh(I) with avidin is an asymmetric catalyst for the N,N-dimethylaniline was usedwithout cation. hydrogenation of a-acetamidoacrylic The acid. other Diphenylphosphine was prepared by literature procedures.r3 rhodium-protein conjugatesdo not exhibit enantioselec- Bis[2-(diphenylphosphino)ethyl]amine (l). Diphenyl- tivity in the hydrogenation of this substrate. ph
Anal. Calcd for C37HgN1O5P2:C, 70.13;H, 5.25;N, 2.21. 3360(vs, br), 1640(s). 1550 (m) cm I. Found: C, 69.89;H, 5.31;N, 2.32. This material was extremely Preparation of Compound 19. In an argon-flushed.250-mL hygroscopicand was stored under vacuum to prevent hydration. flask equippedwith a stirring bar and addition funnel were placed Sodium Taurinate. In a 1-L flask was suspended55.0 g (aa} 0.353g (2.00mmol) of tricarballvlic anhl'dride acid chlorideand mmol) of taurine in 550 mL of absolutemethanol. To the vig- 80 mL of dry CH2CI2.The mixture wasstirred until dissolution orously stirred mixture was slowly added 23.0S (426 mmol) of was complete. The addition funnel was chargedrvith a solution solid sodium methoxide. After the mixture was stined at ambient of 0.96g (2.00mmol) of I.HCI and 0.51mL (0.-19g. 1.0 mmol) temperature for 24 h, the residual solids were removed by fil- of l{,N-dimethvlaniline in 20 mL of CH2CI2,and this was added tration, and the solvent was removed under reduced pressureto dropwise to the acid chloride solution at 0 oC with vigorous give the product in quantitative yield. stirring. The reaction was warmed slowly to ambient temperature Preparation of Compound 18. In a 100-mLflask, under an and stirred overnight. Examination of an aliquot by IR showed argon stream,were placed 1.00g (1.63mmol) of 5, a stirring bar, clean formation of the anhydride amide 6: 1850(m), 1780 (vs), and severalglass beads. Into this mixture, with vigorousstirring, 1635(s) cm r. The solution was filtered under argon,the volume was poured a solution of 1.00g (6.80 mmol) of sodium taurinate reduced to -20 mL, and the resulting solution then added with dissolvedin 30 mL of degassed,absolute methanol. The sudsy vigorous stirring to a solution of 3,82 g (16.0 mmol) of N-(2- solution and white precipitate that formed were stirred for 20 h aminoethyl)gluconamidein 20 mL of distilled water in a thin, at ambient temperature. The methanol was removed under continuousstream (ca.8 min to completeaddition). The frothy reduced pressure,and the white solids produced were extracted mixture was stirred for 6 h at ambient temperature, and the with portions (6 x 100 mL) of CHCI3 under argon. The combined methylene chloride was evaporatedcarefully (foaming) under organic phases were filtered and the volatiles removed under reducedpressure. The aqueoussolution was cooledto 0 oC and reducedpressure to give 1.2g (95n) of 18: IR (CH2CI2)1712 (w), slowly acidified kr pH - 1.0by dropwiseaddition of concentrated 1625(vs), 1595(vs), 1200 (vs), 1050 (s) cm 1. The lH NMR spectra HCI. The white solid that precipitated was collectedby filtration, were difficult to interpret due to extremely broad line widths found washedquicklv with 5 mL of saturated aqueousNaCl, 1 mL of in all solvents in which 6 dissolved. In general,aromatic and H2O,and pxrrtionsQ x 5 mL) of 2:\ (v lv) EteO lCH2Cl2,and dried aliphatic resonancesshowing little structure are observed. In D2O under reducedpressure (0.05 torr) for 7 days at ambient tem- low levelsof taurine are observed:31P NMR (H2O)-21.4 (s),-23.1 peratureto give 1.2g (7:)Vclof an off-white solid: IR (neat)3300 (s) ppm. (vs,b), 1710(s), 1635 (vs) cm r. Anal. Calcdfor QeH36N2Na2O7Pf,: C, 59.69;H,4.62; N, 3.57. Anal. Calcd for Ca2H.lNrOroP::C, 61.53;H, 6.08;N, 5.13. The data suggestsodium taurinate ((0.2 molar equiv) to be the Found: C, 60.85;H, 6.08;N, 5.3-1(this material may be partially major impurity present [Found: C, 58.17;H, 4.51; N, 3.87]. hydrated). Tricarballylic a,B-Anhydride. In a 500-mL flask protected Preparation of Compound 20. Compound6 wasprepared from atmospheric moisture was placed 76.6 g (0.435mmol) of by proceduressimilar to those describedin the preparation of tricarballylic acid. Acetic anhydride (41.0mL, 44.49,0.435 mmol) 19 (at half the scaledescribed). The solutionof 6 (- 1.0mmol) was added, with stirring, in one portion. The reaction mixture thus obtainedwas evaporated to drmess under reducedpressure was heated to 45 oC and becamehomogeneous after 20 min at and treated while beingstirred vigorousl-'-with a solution of 0.75 this temperature. After t h the reaction solidified. A 150-mL g (5.1 mmol) of sodium taurinate in 30 mL of methanol. The portion of glacial acetic acid was added and the mixture heated reaction was stirred under argon for 24 h, the volatiles were to 65 oC for t h to give a homogeneoussolution. Slow cooling removedunder reducedpressure, and the solidswere extracted to ambient temperature gavea copious,white, microcrystalline with portions (8 x 100 mL) of CHCI3/MeOH (2.5:l v/v) and powder. The solid was collected by filtration, washedwith portions CH2CI2(4 x 100 mL). The combined organic extracts were (4 x 100 mL) of ether, and dried in vacuo to give 60.4 g (87%) evaporated under reduced pressureto give an oily material which, of producl mp 133-135'C (lit.lEmp 133-134oC); IR (Fluorolube) when washedwith 50 mL of ether, gave 0.64 g of a white, hy- 1855(m), 1780(vs), 1700(s) cm t. groscopic,semicrystalline solid: IR (neat) 3450 (s), 1630 (s), 1580 Tricarballylic a,B-Anhydride Acid Chloride. In a 100-mL (s), 1200(s), 1050(m) cm 1;31P NMR 20.9(s), -22.1 (s) ppm. flask containing 50 mL of thionyl chloride was suspended11.1 The lH NMR in D2O spectrashowed a seriesof broad resonances g (70.2 mmol) of tricarballylic a,p-anhydride under argon. To and significant levels of excess taurine. Anal. Calcd for the gently stirred mixture was added 6 drops of dimethylform- C36H3sN2Na2O7P2S1:C, 57.60; H, 5.10;N, 3.73. Found: C, 47.58; amide, and the reaction was heated to 45 "C. A vigorousreaction H, 4.85;N, 4.11. (Theseanalyses indicate that slightly greater ensued,and heating was applied intermittently to maintain ev- than 1 molar equiv of sodium taurinate remainsin the prepila- olution of gassesover an -2-h period, grving a homogeneousyellow tion.) The mixture was purified further by dissolving the product solution. The excessthionyl chloride was removed under reduced under argon in 8 mL of H2O, cooling to 0 oC, adding 10 mL of pressure,and portions (3 x 30 mL) of CH2CI2were sequentially n-pentane,stirring the mixture vigorously, and precipitating the added and evaporated under reduced pressure to complete its product by slow. dropwise addition of concentratedHCI. The removal. The white paste obtained was recrystallized twice from liquids were decanted from the white gum that formed. This a minimum of hot CH2CI2to give 7.5 g (61To)of white crystals. material was then washedwith 1.0 mL of 1.0 M HCI and extracted This compound was stored in a desiccatorat -10 oC when not into 10 mL of CH2CI2. The organic phasewas separated,con- in use: IR (CH2CI, 1865(m), 1790(vs) with a shoulderat 1780 centrated, and dried under reduced pressureto give 0.36g (49Vo, (s) cm-l; massspectrum, mf e 41 (M+ - Cl,2 CO, CO2,base peak), if pure) of a white, microcrvstallinepowder: IR (neat) 3400-2500 141(M+ - Cl), 132(M* - COt, 113,99, 76, 69, 63, 55 (no molecular (s),1705 (s), 1630 (vs), 1170 (vs), 1025 (s) cm-l; 31PNMR (HrO, ion is observed). pH -8.0) -20.8 (s),-22.'2 (s) ppm. N-(2-Aminoethyl)gluconamide. Into a 100-mL Erlenmeyer Anal. Calcdfor C36H1eN2NaO7P2S1:C, 59.33; H, 5.39;N, 3.84. flask containing 55 mL of ethylenediaminewas added 2.50g (14.0 Found: C, 57.56;H, 5.63;N, 3.57(this material is believedto be mmol) of o-glucono-D-lactonewith vigorous stirring, and the re- hydrated). action mixture was flushed quickly with argon. An exothermic Preparation of Compound 21. A solution of p-sulfamyl- reaction ensued, and eventually a homogeneoussolution was benzoylchloride 0.725 g, 3.30mmol) in 20 mL of THF was added formed. After stirring for 24h at ambient temperature, the excess to a solution of 1.57g (3.30mmol) of l.HCl and 1.0mL of pyridine diamine was removed under reducedpressure (0.05 torr), and the in 20 mL of THF. After the mixture was stirred for 20 h at glassymaterial thus obtained was dried under reduced pressure ambient temperature, 30 mL of H2O was poured into the solution. (0.05ton) for 20 h at 60 oC. Analysis by lH NMR showedresidual The mixture was extracted with 20 mL of benzene,and the extract diamine in the preparation. For removal of this contaminant, was washedwith 100 mL of 2 N HCI and 100 mL of saturated the solid was extracted with portions (8 x 100 mL) of absolute aqueousNaCl. The solution was dried over Na2SOa,filtered, and diethyl ether, agitating each extraction in an ultrasonic bath for evaporated to give a gummy material which recrystallized from 30 min. The solids thus obtained were dried under reduced 20Vo aqueousmethanol as an off-white powder: 42% yield (0.79 pressure (0.05torr) for 3 days to give 3.3 g of a light yellow glass. g); rH NMR (CDCI3)6 1.8-2.8(m, 4 H), 3.0-3.9(m,4 H), 5.7(., This mixture was not purified further: rH NMR (D2O) 6 2.7 (t, 2 H) 6.8-7.9(m, 24H); IR (CDCls)3425 (s),3340 (s), 1622(s), 2 H),3.4 (t, 2 H), 3.5-4.3(m, -g H), 4.4 (d, -1 H); IR (neat) 1350(s), 1160 (m) cm I. Functional Chelating Diphosphines J. Org. Chem., Vol. 46, No. 14, 1981 2867
Anal. Calcd for C35H3aN2O3P2S:C, 67.30;H, b.49;N, 4.48. (s),1480, 1435 (s) cm t; NMR (CDCU 6 7.3 (m, 8.8H),6.4-5.3 Found: C, 67.28;H, 5.64;N, 4.31. (m, 1 H),3.6-3.1(m, 2 H), 2.I-2.4 (m, 2 H). Although it is obvious Preparation of Compound 22. The procedureand sca_leused from NMR and TLC analysesthat 24 is not pure, this material were similar to that describedfor the preparation of 15. The was used without further purification. product is initially obtained as a waxy gum and can be recrys- Preparation of Compound 25. The amide anhydride 5 (L62 tallized from ethanol to give 70 mg (:70%)of a white solid: mp mg,0.264mmol) and n-octadecylamine(71 mg,0.264 oC; 'H mmol) were 2L3-2L3.5 NMR (CDCIJ 6 L.7,2.8(br m,8 H), 2.8-3.9(br placed in separateround-bottomed flasks which were stoppered m, 8 H), 6.7-7.7(m,44 H); IR (Nujol) 1633cm-l. and flushed with argon for 30 min. Both solids were dissolved Preparation of Compound 23. Polyethyleneglycol mono- in 4.0 mL of dry methylene chloride and the mixtures vigorously methyl ethyl ether (averagemol wt 550; 59 g,0.11 mol) was stirred for severalminutes before dropwise addition of the amine dissolvedin 100mL of pyridine, and thionyl chloride (10 mL, 0.14) solution to the flask containing the anhydride. The yellow oily was added dropwiseover a period of 10 min. After the exothermic mixture was stirred for at least 2 h at room temperature under reaction subsided,the solution was poured into 500 mL of ether, a static atmosphereof argon. The solvent was removed under and the ether layer was decanted from the insoluble residuethat reduced pressureby using a rotary evaporator (20 torr) and high was deposited. The residuewas extracted with portions (3 x b00 vacuum (0.05torr) to afford in quantitative yield (233 mg) a pale mL) of ether, the combined organic phaseswere neutralizedby yellow glass. The glasswas characterizedby its NMR and IR washing with saturated aqueousNaHCO3, and the volatiles were spectra and was used in hydrogenation reactionswithout further removed under reduced pressureto give a brown oil. The oil was purification: IR (neat,oil) 2980,2900(s), 1725 (m),1640 (s, br), dissolved in methylene chloride, decolorized with activated 1590(m), 1,170,1.1-10 (m) cm-l;NMR (CDCIJ 6 ?.0-?.8(m, 20 H), charcoal (Fischer Darco), filtered, passedthrough a 1 X 8 cm 2.0 3.9(m, 1.0H), 1.3(m,3.5 H). column of Woelm activity I neutral alumina, and evaporatedunder Preparation of Metal Complexes. Nickel dichloridecom- reducedpressure to give a clearoil (20.8g, BIVo). Part of this plexes of the phosphinesdescribed above were prepared by material (I2 g,21 mmol) was dissolvedin 30 mL of THF and modificationof literature procedures.le Platinum dichloride added dropwise to a stirred solution of potassium diphenyl- complexeswere prepared by standard proceduresby reacting phosphide, prepared by reaction of 3.7 g (2I mmol) of di- (COD)PtCl220under argonwith a slight excessof the ligand in phenylphosphinewith 0.65g (21 mmol) of potassiumhydride in THF for 48 h; the products were isolated oC. as THF-insoluble 30 mL of THF at 0 The reaction was stirred for t h and precipitatesby filtration. Preparationof cationic rhodium com- quenchedby addition of 2 mL of water to the reactionmlxture. plexesand subsequentcatalyses performed with them were ef- The reactionwas diluted with 500 mL of ether, filtered through fected bv proceduresanalogous to those already described.a 100g of Woelm activity I neutral alumina, and crystallizedat ;8 oC to give a yellow oil at room temperature. This material q'as Acknowledgment. We thank Dr. David Feitler, who (0.05 dried under reduced pressure torr, 20 h) to gir..et 1 g of prrepared 23 and initiated our studies in homogeneous product. The 3tP NMR (6 - suggestedthat l l 22.8)comprised hvdrogenations in aqueous solution. 85% of the phosphorus-containingspecies present. Anal. ,1.30. Calcdfor C37H61O12P:C,61.06; H, 8.46;P, F.ound: Registry No. l.HCl, 66534-97-22, 1204-28-0;3, 77461-97-3;4, C, 60.50;H, 8.45;P, 3.06. r1-08-;l;5, 71120-43-9;6, 77461-98-4; 7.Na, 7746I-99-5; 10, 66b61- Preparation of N,,V-Bis[2-(diphenylphosphino)ethyl ]- 97-5;I l. 66536-67-2; 12,66561-98-6; L3, 77 519-44-9; 15, 6653a-91-6; acrylamide (24). In a 25-mL flask wasdissolved l.HCl (465mg, I 6. 66534-94-9; 17, 77 462-00-l; I 8.2Na, 77 462-01-2;Ig, 77 462-02-3; 0.975mmol) in 15 mL of dry methylenechloride. Distilled tri- 20.Na, i 7462-03- 4; 20.2Na,7 7 462-04-5; 2 1,66534-9 2-7 ; 22,66534-93-8; ethylamine (0.275mL, 2.0 mmol) was injected into the flask, and 23, 77 461-22- 4; 24, 77 462-05-6;25, 77 462-06-7; diphenylphosphine, the solution was stirred for 15 min at room temperature. The 829-85-6;bis(2-chloroethyl)amine HCl, 821-48-?;N-biotinoxysuccin- reaction vesselwas immersed in an acetone/dry ice bath. Acryloyl imide, 35013-72-0;a-(chlorocarbonyl)-<,r-methoxypoly(oxy-1,2- chloride (0.078mL,0.975 mmol) wasadded dropwiseover a period ethanediyl),51023-28-0; phenyl isocyanate,103-? 1-9; o-camphoric of 3 min, and the solution was stirred for an additional 5 min anhydride,595-29-9; acetyl chloride,75-36-5; succinic anhydride, -25-3; before the flask was allowed to warm to ambient temperature. 108- 30- 5 ; taurine,1 07-35-7 ; sodium taurinate, 7 347 tricarballylic ,r.,i-anhydride, The solution was washedwith 10% hydrogen chloride (B x 25 4756-10-9; tricarballylic acid, 99-14-9; N-(2-amino- ethvl)gluconamide,74426-36-l; mL) and distilled water (2 x 25 mL). The methylenechloride ethylenediamine,10?-15-3; o- glucono-6-lactone,90-80-2; p-sulfamylbenzoyl chloride, 51594-9?-9; layer was dried over anhydrous sodium sulfate for 4b min under terephthaloylchloride, 100-20-9; a-(2-chloroethyl)-<,r-methoxypoly- a moderate stream of argon before filtration. solvent was removed i