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Organophosphorus Chemistry (Kanda, 2019) Baran lab Group Meeting Yuzuru Kanda Organophosphorus Chemistry 09/20/19 bonding and non-bonding MOs of PH3 bonding and non-bonding MOs of PH5 # of R P(III) ← → P(V) O P P R R R R R R phosphine phosphine oxide D3h C3v C2v O O JACS. 1972, 3047. P P P P R NH R OH R OH R NH Chem. Rev. 1994, 1339. R 2 R R R 2 D C phosphineamine phosphinite phosphinate phosphinamide 3h 4v O O O R P R P R P R P R P R P NH2 NH2 OH OH NH2 NH2 H2N HO HO HO HO H2N phosphinediamine phosphonamidite phosphonite phosphonate phosphonamidate phosphonamide O O O O H N P P P P P P P P 2 NH HO HO HO HO HO HO H2N H N 2 NH2 NH2 OH OH NH2 NH2 NH2 2 H2N HO HO HO HO H2N H2N phosphinetriamine phosphorodiamidite phosphoramidite phosphite phosphate phosphoramidate phosphorodiamidate phosphoramide more N O more O Useful Resources more N P P P Corbridge, D. E. C. Phosphorus: Chemistry, Biochemistry and H OH H H H H H H H Technology, 6th ed.; CRC Press Majoral, J. P. New Aspects In Phosphorus Chemistry III.; Springer phosphinous phosphane phosphane Murphy, P. J. Organophosphorus Reagents.; Oxford acid oxide Hartley, F. R. The chemistry of organophosphorus compounds, O O volume 1-3.; Wiley P P P Cadogan. J. I. G. Organophosphorus Reagents in Organic H OH H OH H OH HO HO H Synthesis.; Academic Pr phosphonate phosphonus acid phosphinate Not Going to Cover ↔ (phosphite) Related GMs Metal complexes, FLP, OPV Highlights in Peptide and Protein NH S R • oxidation state +5, +4, +3, +2, +1, 0, -1, -2, -3 Synthesis (Malins, 2016) R P-Stereogenic Compounds P P R P • traditionally both +3 and -3 are written as (III) R • 13/25th most abundant element on the earth (Rosen, 2014) R • but extremely rare outside of our solar system Ligands in Transition Metal phosphine imide phosphine sulfide phosphorane Catalysis (Farmer, 2016) Baran lab Group Meeting Yuzuru Kanda Organophosphorus Chemistry 09/20/19 Me P Me Me Low-Coordinate Low Oxidation State P tBu tBu P P phosphaalkyne R N P PivCl 2 P Me Cl TMS OTMS NaOH R = tBu Nb N tBu PTMS3 P O H O P NR2 then Na/Hg tBu N -2 Nb tBu R2N Me Nb N tBu 5x10 mbar, 160 ºC NR2 95% R2N Me N O 1. Tf2O Me Nb 2. Δ tBu R2N O 1. LAH NR2 2. DBU R = Me R2N P recyclable Me EtO HP P R EtO J. Chem. Soc. Chem. JACS. 2000, 13916. Commun. 1992, 415. PPh3 20-80 ºC PPh3 Cl JACS. 2012, 134, 13978. P R P 1. Me2NPCl2 Mg 2. HCl JACS. 2014, 13586. R JACS. 2018, 17985.: P31 nuclear spin- rotation coupling (J = 0←1) (R = Me) R ≠ H, tBu tBu O N R’ tBu Ph O N R' Ph N O Ph Ph R X N P P R N PhMe, tBu P V tBu P [2+1] then O Cl Cl P O 100 ºC, 14 days X 1,3-X shift Cl P P tBu N Ph R R P R Ts tBu tBu P A B C Ts N N P P A C R 2TsN3 P P B [2+3] P N N N Δ or Zr cat R P P N tBu P tBu P R R P tBu P tBu N O N R Ts Ts H O ACIE. 1984, 900. P ene Weidner. S (2002) PhD thesis, University of Kaiserslautern R P R Chem. Rev. 1990, 191. Chem. Rev. 1990, 191. JACS. 1982, 4484. ACIE. 1987, 1257. ACIE 1989, Et3N Et3N LnM R ML [2+2] 225. Phosphorus Sulfur. 1987, 479. Bull. Soc. Chem. Br Br P P P n THF, -5 ºC Br THF, 40 ºC Fr. 1995, 652. Synthesis. 1998, 125. ACIE. 1986, Br Br P Br M = Co, Rh, Hf, Zr 644. ACIE, 1988. 1157. Chem. Ber. 1988, 637. ACIE. P TL. 1989 817. R Br Br 1995, 2227. ACIE. 1998, 1233. Chem. Eur. J. 2000, Polyhedron. 1990, 991 4558. ACIE. 1989, 1013. ACIE. 1992, 758. Baran lab Group Meeting Yuzuru Kanda Organophosphorus Chemistry 09/20/19 Phosphide Anion C, SiO2 1200-1400 ºC • reduction of energy inputs O O Cl2 O • less waste O HSiCl3 (neat) versatile 1 Mt/y O P P O • no elemental P P P organophosphorus O O 110 ºC, 72 h Cl Si SiCl • no Cl2 oxidation P O O 3 3 precursor 65%, gram scale O O •3TBA•2H2O O O Ph O 1. [TBA]3[P3O9]•2H2O, P Cl HSiCl , 64% (one-pot) P N 3 H Cy O O O H2SO4 HO 2. H O 2 2 HO2C Ph Ph Me Me Me 90 Mt/y fosinopril Direct Method original prep: 4-phenyl-1-butene, H3PO2, AIBN, 93% contaminated w/ 2% anti-Markovnikov regioisomer H3PO4, TBACl Oct Cl Oct PH2 JACS. 2019, 6375. OPRD. 1997, 315. Science 2018, 1383. JACS. 2019, 6375. HSiCl3, 110 ºC P-P bonds for detail see; Corbridge, D. E. C. Phosphorus: Chemistry, Low-Coordinate Hypervalent Phosphorus useful reviews Biochemistry and Technology, 6th ed.; CRC Press JACS. 1987, 627. Chem. Rev. 1994, 1215. TIPS P tBu tBu tBu tBu O O O O tBu Nb XH N N tBu X if X = OR N TIPS -2 tBu Ar Ar N P N P N P N P Phospha-Wittig P PMo(N[tBu]Ar) TIPS H O Ar 3 OR P P P O O reductive O O P tBu TIPS elimination tBu N Mo tBu tBu tBu tBu Mo tBu N tBu if X = H stable if N tBu N tBu N Ar JACS. 2009, 8764. X = H, NHR N Ar 10-P-3 ADPO R Ar Ar Ar N P • T-shaped O Ar O O hν P Me • strongly reducing N P iPrOH P OiPr P P P • formally dianionic P O O N P Me tBu P P hex, DMSO tBu • pseudo-TBP H P 15% (34% brsm) 8-P-3 8-P-3 Me Me Me O Me ACIE. 2010, 7516. w/o unsaturation JACS. 2014, 13586. 10-P3 not observed R stable Cl 1. AlCl P 3 2. LAH P Δ OH O O P P(OMe)3 H BH3•DMS 55% For P2 surrogate also see; NH N P N P Science 2006, 1276. OMe instead BH adduct recall: phosphaalkyne precursor 3 Inorg. Chem. 2007, 7387. OH O dimer was isolated - O P3 ; ACIE. 2010, 1595. Baran lab Group Meeting Yuzuru Kanda Organophosphorus Chemistry 09/20/19 R = H active reductant tBu stepwise tBu R = Pr, O oxidative Naph Naph R R O= 2,6-diiPrC6H3 N N addition N N P NH R R H P 2 N H Me H Me ADPO N P N N R Me Me H H N P first-order w/ H no H cat. 1 mol%, HBpin ADPO, [NH R]3 O RH2N reductive N N 2 O H tBu elimination 91% JACS. 2019, 14083. tBu Ar N Br 91:1 er N Br also see; JACS. 2018, 652. tBu tBu tBu N H O O Ar Phosphine Me Ph P P H H N NH NH2 miscellaneous phosphine synthesis; for more info see GM by Rosen (2014) NH Bn N 3 N 2 N Ar P P tBu Ar N P N P P R R H Me H rt N 3RX P tBu tBu Ar P P N N Ar Ti tBu benzene, rt R O NH2iPr O Ar = 2,6-diiPrC H P 6 3 tBu N 64-97% tBu tBu JACS. 2014, 4640. tBu 3,5-Me2C6H3 New J. Chem., 2010, 1533. other oxidative addition reactivities of ADPO JACS. 2014, 16764 R = Ph, Cy, TMS, Ph3Sn Org. Chem. Front. 2018, 3421. tBu Ph Cl 1. Et N O O O Cl O N P 3 P F 2. H O CO Et Cl O O O Br 2 2 F F C P N CO Et N P CF O 3 H 2 3 F C Ph 3. HSCH2CH2SH, S F 3 tBu Br O Cl F C O BF3•Et2O tBu P O 3 S O O O 4. Raney-Ni tBu O O 5. LAH tBu F O F N P 6. HCl NaOH F3C CF3 Ph w/ F CF3 w/ o-chloranil w/ Heteroat. Chem. 1993, 213. JACS. 1987, 627. JACS. 1987, 627. P P CF3 tBu Na spiro conjugation O N P O CF3 Tet. 1983, 4225. O CF 3 N P CN F C CF3 N P 3 H [2+3] CF3 Ph chemische berichte, CF3 CF3 N2 CF3 tBu CF Ph NaOMe 1966, 514. CF O 3 Ar P F C CF Δ O 3 Ph w/ 3 3 tBu P P tBu Ph CN JACS. 1987, 627. D symmetric orbitals Ph 2d π Ph NO2 NO JACS. 1967, 5208. S ≈ 20% of planar system 2 Phosphenium Cation; Chem. Rev. 1985, 367. styrene (10 eq), via tBu Me4NF (15 mol%), tBu P(CH OH) P Ph 2 3 [FpTHF][BF4] (10 mol%) P N P N P N tBu Fe CO BF 73%, >99:1 dr F 4 CH O BF4 CO Ph 2 Me Me ACIE. 1964, 384. Me JACS. 2019, 13336. Baran lab Group Meeting Yuzuru Kanda Organophosphorus Chemistry 09/20/19 Me Me Me Me 1. PhCCCO Me NHCbz 2 NHCbz Ph3P, Ph3P•HClO4 NHCbz Me Me 2. S PPh3 PhPX2 Δ 8 R Ar R CO2H 5 mA, DCM, -30 ºC R CHO P P O (+)graphite/(-)graphite TL.
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