Application Guide – Phosphine Ligands Phosphine Ligand Application Guide 2 Phosphine Ligands Transition-metal-catalyzed cross-coupling is an efficient tool for constructing C–C, C–N and C–O bonds in organic synthesis. Intensive interest has been focused on the development of the most effective ligands that improve catalyst performance. Ligands play a key role in stabilizing and activating the central metal atom and fine-tuning the selectivity of the transformation. Phosphines continue to be the most significant class of ligands for cross coupling. This brochure highlights the common applications and advantages of monodentate, bidentate, Buchwald, cataCXium®, and Dalphos ligands, all of which are commercially available from Aldrich Chemistry. Monodentate Phosphine Ligands and Precursors Structure and Cat. No. Common Name CAS No. Mol. Wt. Negishi Suzuki Stille Heck Sonogashira Buchwald-Hartwig or C–O) (C–N Additional Applications PPh3 603-35-0 262.29 X X X X X • Morita-Baylis-Hillman reaction P 93090 93092 T84409 CH 3 PMe3 594-09-2 76.08 • Mitsunobu reaction P Transformation of azides into carbamates H3C CH3 • Aziridines from azidoalcohols 323322 • Reagent for iminophosphoranes 324108 (1.0 M in THF) • Aza-Wittig reaction 324116 (1.0 M in toluene) • CH 3 PEt3 554-70-1 118.16 • α-Arylation of ketones H3C P CH3 346179 (1.0 M in THF) 245275 H3C P CH3 P(n-Bu)3 998-40-3 202.32 X • 1,4-addition Acylation CH • 3 • Thioetherification of alcohols T49484 • Preparation of active esters 247049 t-Bu P(t-Bu)3 13716-12-6 202.32 X X X X X X • Addition of organoboronic acids to P aldehydes t-Bu t-Bu Addition of alkynes to benzoylchlorides 570958 • 655325 (1.0 M in toluene) t-Bu TTBP · HBF4 131274-22-1 290.13 X X X X X X • Precusor for P(t-Bu)3 - t-Bu P t-Bu BF4 • Carbonylation H • Addition of boronate esters to alkynes and 578940 alkenes CH2(CH2)6CH3 P(n-Oct)3 4731-53-7 370.64 • Surfactant for nanomaterial and nanocrystal CH3(CH2)6CH2 P synthesis CH2(CH2)6CH3 • A general phosphorus source for the 117854 low-temperature conversion of metals into 718165 metal phosphides PCy3 2622-14-2 280.43 X X X • Hiyama coupling • Krische formal [4+2] of dienes and vicinal diols P 261971 PCy3·HBF4 58656-04-5 368.24 X X X • Control regiochemistry of hydrostannations of 1-alkynes Intramolecular arylation P H BF • 4 • Synthesis of indolines from N-alkyl-2- bromoanilines 631493 Aldrich.com Order 800-325-3010 Technical Service 800-325-5832 Phosphine Ligand Application Guide 3 Structure and Cat. No. Common Name CAS No. Mol. Wt. Negishi Suzuki Stille Heck Sonogashira Buchwald-Hartwig or C–O) (C–N Additional Applications P(o-tol)3 6163-58-2 304.37 X X X X X • Silylation CH3 CH3 P H3C 287822 CH3 Me2PPh 672-66-2 138.15 • Ligand for transition metal complexes P CH3 265020 TFP 5518-52-5 232.17 X X X X X X • Cycloisomerization/oxidation of alcohols O P O O 383767 t-Bu APhos 932710-63-9 265.37 X • A-Phos ligand for cross-coupling P t-Bu H C 3 N CH3 677264 Diphenyl-2-pyridylphosphine 37943-90-1 263.27 • Carbonylations Dehydrogenative coupling N P • • Distannylation • Silylation • Carbostannylation 392960 • Hydration • Mitsunobu reaction HO P OH Tris(hydroxymethyl)phosphine 2767-80-8 124.08 • Precursor for metal complexes OH 177881 H HPCy 829-84-5 198.28 X Precursor for ligands and metal complexes P 2 • 666572 H HPPh2 829-85-6 186.19 • Precusor for the phosphorus-based P alkenation reagents • Source of phosphorus-centered radical 252964 K KPPh2 15475-27-1 224.28 • Precusor for novel sulfur and phosphorus P containing oxazolines used in asymmetric catalysis 380768 Li Ph2PLi 65567-06-8 192.12 • Dealkylation of alkyl aryl ethers P • Dehydroxylation of α-hydroxy ketones 464872 Cl P(i-Pr)2Cl 40244-90-4 152.60 • O-Arylation of phenols P i-Pr i-Pr • Precusor for ligands and metal complexes 337773 H HP(t-Bu) 819-19-2 146.21 X X X Precusor for ligands and metal complexes P 2 • t-Bu t-Bu 362719 Cl P(t-Bu)2Cl 13716-10-4 180.66 X P t-Bu t-Bu 301558 For bulk quantity inquiries contact: [email protected] 4 Monodentate Phosphine Ligands and Precursors – continued Structure and Cat. No. Common Name CAS No. Mol. Wt. Negishi Suzuki Stille Heck Sonogashira Buchwald-Hartwig or C–O) (C–N Additional Applications Cl Cy2PCl 16523-54-9 232.73 • Precusor for phosphine ligands P 481408 OCH 3 P(OMe)3 121-45-9 124.08 X X • Mild desulfurization reagent P H3CO OCH3 92730 240907 O CH3 P(OEt)3 122-52-1 166.16 • Reducing agent P Precusor for phosphonates or phosphates H3C O O CH3 • • Used with copper(I) iodide to form a stable T61204 metal complex Ph O P(OPh)3 101-02-0 310.28 X X • Conversion of alcohols to halides Ph P Ph Wittig-type reaction O O • Deoxygenation T84654 • • Cycloaddition reactions • Allylic alkylations • Cyclohydrocarbonylation/CO insertion • Wittig-type olefinations H3C CH3 2-Chloro-4,4,5,5-tetramethyl- 14812-59-0 182.59 • Reagent for the phosphitylation of alcohols H3C CH3 and heteroatomic nucleophiles O O 1,3,2-dioxaphospholane P Cl 447536 O TOPO® 78-50-2 386.63 • Agent for extraction of metals CH3(CH2)6CH2 P CH2(CH2)6CH3 • Capping ligand for the production of CH2(CH2)6CH3 quantum dots 223301 • Solvent for the synthesis and solubilizes the 346187 growing nanoparticles O HPOPh2 4559-70-0 202.19 X X • Hydrophosphinylation of terminal alkynes P Selective hydrophosphinylation of olefins H • • Precursor for diphenylphosphino- 287881 containing chiral ligands O Ph2POCl 1499-21-4 236.63 • Acid activation P • Alkylphosphine oxide formation Cl • Amine protection 230235 O TPPO 791-28-6 278.28 • Catalyst for allylation of aldehydes or N-aryl P hydrazones • Promoter for coupling reaction of 1-alkenyl with sulfonyl chlorides T84603 • Cocatalyst for enantioselective cyanosilylations • Tuning ligand for asymmetric epoxidation • Scavenger for enantioselective Michael reactions of enones O PhPOCl2 824-72-6 194.98 • Precursor for phosphonate ligands and P Cl metal complexes Cl 389560 i-Pr i-Pr N Di-tert-butyl N,N-diisopro- 137348-86-8 277.38 • Precursor for ligands t-Bu P t-Bu pylphosphoramidite • Reagent for the synthesis of nucleosides O O and nucleotides 419362 i-Pr i-Pr Bis(diisopropylamino)chloro- 56183-63-2 266.79 • Reagent for the synthesis of N N i-Pr P i-Pr phosphine oligonucleotides Cl 341347 Aldrich.com Order 800-325-3010 Technical Service 800-325-5832 Phosphine Ligand Application Guide 5 Structure and Cat. No. Common Name CAS No. Mol. Wt. Negishi Suzuki Stille Heck Sonogashira Buchwald-Hartwig or C–O) (C–N Additional Applications CH3 CH3 HMPT 1608-26-0 163.20 X • Synthesis of epoxides, arene oxides, and N N carbonates H3C P CH3 N Conversion of alcohols to alkyl chlorides H C CH • 3 3 • Conversion of disulfides to sulfides 393290 • Deoxygenation of sulfoxides and azoxyarenes • Reduction of ozonides • Replaces Ph3P in the Wittig reaction CH 3 P(NEt2)3 2283-11-6 247.36 • Precursor for phosphine ligands and metal complexes H3C N P H3C N N CH3 CH3 CH3 253189 CH 3 P(SiMe3)3 15573-38-3 250.54 • Phosphorus source H3C Si CH3 • Alternative to phosphine gas H3C P CH3 Precursor of (Me3Si)2PLi H3C Si Si CH3 • CH3 CH3 333670 Ph Ph CH Triphos 22031-12-5 624.67 • Reagent for metal complexes P 3 P Ph Ph Ph P Ph 380741 Cl PhPCl2 644-97-3 178.98 • Precursor for phosphine ligands P Cl D71984 H3C P CH3 Et2PCl 686-69-1 124.55 • Precursor for phosphine ligands Cl 573949 BippyPhos 894086-00-1 506.62 X Amidation t-Bu N • P N Ph • Coupling of hydroxylamines with aryl t-Bu halides N Ph N Ph 676632 t-Bu QPhos 312959-24-3 710.71 X X X • α-Arylation of esters, amides and aldehydes P t-Bu Fe Ph Ph Ph Ph Ph 675784 N PTA 53597-69-6 157.15 X X • Morita–Baylis–Hillman reactions NN • Hydrogenations P • Olefin hydroformylations 695467 • Cyclization Bis(p-sulfonatophenyl) 151888-20-9 534.62 X phenylphosphine dihydrate P dipotassium salt O O KO S S OK O • 2H2O O 698539 6-DPPon 64741-28-2 279.1 • New Breit’s Regioselective Hydroformylation H • P N O Ligand RNI00061 For bulk quantity inquiries contact: [email protected] 6 Bidentate Phosphine Ligands and Precursors Structure and Cat. No. Common Name CAS No. Mol. Wt. Negishi Suzuki Stille Heck Sonogashira Buchwald-Hartwig or C–O) (C–N Additional Applications H3C CH3 XantPhos 161265-03-8 578.62 X X X • C-P bond formation • Regioselective hydroformylation of O allylamines P P • Borylation of nitriles Ph Ph Ph Ph 526460 Ph Ph Ph Ph P P DPEPhos 166330-10-5 538.55 X X X X • Hydroamination O 510017 (±)-BINAP 98327-87-8 622.67 X X Intramolecular acylation of aryl bromides Ph • P Ph • Minisci reaction with alcohols • Decarboxylative benzylation of P Ph diphenylglycinate Imines Ph • Regioselective hydroarylation 481084 • Decarboxylative cycloaddition • S-arylation (S)-SEGPHOS® 210169-54-3 610.57 • Stereoselective preparation of homoallylic O alcohols via Ir-catalyzed stereoselective transfer hydrogenative crotylation of an O P allylic acetate with alcohols or aldehydes O P O 693006 Ph dppbenz 13991-08-7 446.46 • Cycloadditions P Ph • Addition of arylboronic acids Ph Baeyer-Villiger oxidation P • • Reduction of propargyl oxiranes and Ph hydroboration of styrene 460273 Ph dppf 12150-46-8 554.38 X X X X X X • Tsuji-Trost allylation P Carbonylation of vinyl triflates Ph • Ph Fe • Enantioselective ene reaction P • Addition of organoboronic acids to Ph aldehydes 177261 CH3 dmpe 23936-60-9 150.14 • Ligand for metal complexes P CH3 H3C P CH3 261939 Ph Ph dppm 2071-20-7 384.39 X X Ligand for metal complexes P P • Ph Ph 127566 Aldrich.com Order 800-325-3010 Technical Service 800-325-5832 Phosphine Ligand Application Guide 7 Structure and Cat.