pp 1-38 | Cite as

Process Economics and Atom Economy for Industrial Cross Coupling Applications via LnPd(0)-Based Catalysts

  • Eric D. SlackEmail author
  • Peter D. Tancini
  • Thomas J. ColacotEmail author
Part of the Topics in Organometallic Chemistry book series


Up to and beyond the 2010 Nobel Prize in Chemistry, Pd-based cross coupling has seen a boom in industrial applications and scientific research. These efforts have yielded a wealth of information on Pd-based catalyst technology that can be separated into two broad categories: pre-catalysts and in situ generated catalysts. Proper selection of the catalyst system, i.e., in situ vs pre-catalyst is although process dependent, herein we provide an in-depth look into the often overlooked benefits of the pre-catalyst technology for maximizing the process economics. Although ligands play a crucial role in catalysis, it is not “all about ligands” alone. To improve the efficiency of the process one may need to precisely generate the active catalytic species for that particular reaction. In this chapter, we highlighted this concept by providing industrial case studies where switching from in situ generated to pre-catalyst technology yielded significant process economic benefits. We also provided process chemists with a methodology to properly evaluate catalyst technology and make recommendations on potential benefits by weighing the pros and cons of using in situ vs preformed.


Atom economy  Catalyst cycle  Catalyst selection  Cross coupling  In situ catalyst generation Industrial applications LPd(0) Pre-catalysts Preformed Pd complexes Process economics 





















4,5-Bis(diphenylphosphino)-9,9-dimethyl-xanthene [55]


  1. 1.
    Colacot TJ (ed) (2015) New trends in cross-coupling: theory and applications. Royal Society of Chemistry, CambridgeGoogle Scholar
  2. 2.
    Payard P, Perego LA, Ciofini I, Grimaud L (2018). ACS Catal 8:4812Google Scholar
  3. 3.
    Planas O, Whiteoak CJ, Ribas X (2019) In: Gebbinik RJMK, Moret M (eds) Non-noble metal catalysis: molecular approaches and reactions. Wiley, Hoboken, pp 297–328Google Scholar
  4. 4.
    Neidig ML, Carpenter SH, Curran DJ, DeMuth JC, Fleischauer VE, Iannuzzi TE, Neate PGN, Sears JD, Wolford NJ (2019). Acc Chem Res 52:140Google Scholar
  5. 5.
    Hazari N, Melvin PR, Beromi MM (2017). Nat Rev Chem 1:25Google Scholar
  6. 6.
    Li H, Johansson Seechurn CCC, Colacot T (2012). J ACS Catal 2:1147Google Scholar
  7. 7.
    Johansson Seechurn CCC, Kitching MO, Colacot TJ, Snieckus V (2012). Angew Chem Int Ed 51:5062Google Scholar
  8. 8.
    Heijnen D, Gualtierotti J, Hornillos V, Feringa BL (2016). Chem A Eur J 22:3991Google Scholar
  9. 9.
    Pinxterhuis EB, Giannerini M, Hornillos V, Feringa BL (2016). Nat Commun 7:11698Google Scholar
  10. 10.
    DeAngelis A, Colacot TJ (2015) In: Colacot TJ (ed) New trends in cross-coupling. Royal Society of Chemistry, Cambridge, pp 20–66Google Scholar
  11. 11.
    Chartoire A, Nolan SP (2015) In: Colacot TJ (ed) New trends in cross-coupling. Royal Society of Chemistry, Cambridge, pp 139–154Google Scholar
  12. 12.
    Martin R, Buchwald SL (2008). Acc Chem Res 41:1461Google Scholar
  13. 13.
    Jiao J, Nishihara Y (2013) In: Nishihara Y (ed) Applied cross-coupling reactions. Springer, Heidelberg, pp 85–106Google Scholar
  14. 14.
    King AO, Yasuda N (2004) In: Larson RD (ed) Organometallics in process chemistry. Springer, Heidelberg, pp 205–244Google Scholar
  15. 15.
    Ruiz-Castillo P, Buchwald SL (2016). Chem Rev 116:12564Google Scholar
  16. 16.
    Magano J, Dunetz JR (2011). Chem Rev 111:2177Google Scholar
  17. 17.
    Torborg C, Beller M (2009). Adv Synth Catal 351:3027Google Scholar
  18. 18.
    The Nobel Prize in Chemistry (2013) Nobel Media AB 2013. Accessed 16 Apr 2014
  19. 19.
    Biffis A, Centomo P, Zotto AD, Zecca M (2018). Chem Rev 118:2249Google Scholar
  20. 20.
    Gildner PG, Colacot TJ (2015). Organometallics 34(23):5497Google Scholar
  21. 21.
    Ritter SK (2016). Chem Eng News 94:20Google Scholar
  22. 22.
    Busacca CA, Fandrick DR, Song JJ, Senanayake CH (2011). Adv Syn Cat 353:1825Google Scholar
  23. 23.
    Dhangar G, Serrano JL, Schulzke C, Gunturu KC, Kapdi AR (2017). ACS Omega 2:3144Google Scholar
  24. 24.
    Jung BJ, Tremblay NJ, Yeh M, Katz HE (2011). Chem Mater 23:568Google Scholar
  25. 25.
    Boudreault PLT, Najari A, Leclerc M (2011). Chem Mater 23:45Google Scholar
  26. 26.
    Takimiya K, Osaka I, Nakano M (2014). Chem Mater 26:587Google Scholar
  27. 27.
    Brocklehurst CE, Gallou F, Hartwieg JCD, Palmieri M, Rufle D (2018). Org Process Res Dev 22:1453Google Scholar
  28. 28.
    Higginson PD, Sach NW (2004). Org Process Res Dev 8:1009Google Scholar
  29. 29.
    Gillmore AT, Badland M, Crook CL, Castro NM, Critcher DJ, Fussell SJ, Jones KJ, Jones MC, Kougoulos E, Mathew JS, McMillan L, Pearce JE, Rawlinson FL, Sherlock AE, Walton R (2012). Org Process Res Dev 16:1897Google Scholar
  30. 30.
    Colacot TJ, Shea HA (2004). Org Lett 6:3731Google Scholar
  31. 31.
    Hayashi T, Konishi M, Kumada M (1979). Tetrahedron Lett 20:1871Google Scholar
  32. 32.
    Organ MG, Avola S, Dubovyk I, Hadei N, Kantchev EAB, O’Brien CJ, Valente C (2006). Chem A Eur J 12:4749Google Scholar
  33. 33.
    Nasielski J, Hadei N, Achonduh G, Kantchev EAB, O’Brien CJ, Lough A, Organ MG (2010). Chem A Eur J 16:10844Google Scholar
  34. 34.
    Bruneau A, Roche M, Alami M, Messaoudi S (2015). ACS Catal 5:1386Google Scholar
  35. 35.
    Stambuli JP, Kuwano R, Hartwig JF (2002). Angew Chem Int Ed 41(24):4746Google Scholar
  36. 36.
    Diehl CJ, Scattolin T, Englert U, Schoenebeck F (2019). Angew Chem Int Ed 58:211Google Scholar
  37. 37.
    Johansson Seechurn CCC, Sperger T, Scrase TG, Schoenebeck F, Colacot TJ (2017). J Am Chem Soc 139:5194Google Scholar
  38. 38.
    Kuwano R, Utsunomiya M, Hartwig JF (2002). J Org Chem 67(18):6479Google Scholar
  39. 39.
    Kalvet I, Sperger T, Scattolin T, Magnin G, Schoenebeck F (2017). Angew Chem Int Ed 56:7078Google Scholar
  40. 40.
    Proutiere F, Schoenebeck F (2011). Angew Chem Int Ed 50:8192Google Scholar
  41. 41.
    Hill LL, Crowell JL, Tutwiler SL, Massie NL, Hines CC, Griffin ST, Rogers RD, Shaughnessy KH, Grasa GA, Johansson Seechurn CCC, Li H, Colacot TJ, Chou J, Woltermann CJ (2010). J Org Chem 75:6477Google Scholar
  42. 42.
    Johansson Seechurn CCC, Parisel SL, Colacot TJ (2011). J Org Chem 76:7918Google Scholar
  43. 43.
    Crabtree RH (2015). Chem Rev 115:127Google Scholar
  44. 44.
    Mitchell EA, Jessop PG, Baird MC (2009). Organometallics 28:6732Google Scholar
  45. 45.
    Yunker LPE, Ahmadi Z, Logan JR, Wu W, Li T, Martindale A, Oliver AG, McIndoe JS (2018). Organometallics 37:4297Google Scholar
  46. 46.
    Mitchell EA, Baird MC (2007). Organometallics 26:5230Google Scholar
  47. 47.
    Stambuli JP, Incarvito CD, Bühl M, Hartwig JF (2004). J Am Chem Soc 126:1184Google Scholar
  48. 48.
    Christmann U, Vilar R (2005). Angew Chem Int Ed 44:366Google Scholar
  49. 49.
    Li Z, Fu Y, Guo Q, Liu L (2008). Organometallics 27:4043Google Scholar
  50. 50.
    Ahlquist M, Fristrup P, Tanner D, Norrby P (2006). Organometallics 25:2066Google Scholar
  51. 51.
    Wang Y, Przyuski K, Roemmele RC, Hudkins RL, Bakale RP (2013). Org Process Res Dev 17:846Google Scholar
  52. 52.
    Ozawa F, Akihiko K, Hayashi T (1992). Chem Lett 21:2177Google Scholar
  53. 53.
    Amatore C, Jutand A, Thuilliez A (2001). Organometallics 20:3241Google Scholar
  54. 54.
    Amatore C, Broeker G, Jutand A, Khalil F (1997). J Am Chem Soc 119:5176Google Scholar
  55. 55.
    Fu GC (2008). Acc Chem Res 41:1555Google Scholar
  56. 56.
    Littke AF, Fu GC (2002). Angew Chem Int Ed 41:4176Google Scholar
  57. 57.
    Hills ID, Netherton MR, Fu GC (2003). Angew Chem Int Ed 42:5749Google Scholar
  58. 58.
    Surry DS, Buchwald SL (2008). Angew Chem Int Ed 47:6338Google Scholar
  59. 59.
    Devendar P, Qu R, Kang W, He B, Yang G (2018). J Agric Food Chem 66:8914Google Scholar
  60. 60.
    Shockley SE, Holder JC, Stoltz BM (2015). Org Process Res Dev 19:974Google Scholar
  61. 61.
    Ye J, Ma S (2014). Acc Chem Res 47:989Google Scholar
  62. 62.
    Khan F, Dlugosch M, Liu X, Banwell MG (2018). Acc Chem Res 51:1784Google Scholar
  63. 63.
    He G, Wang B, Nack WA, Chen G (2016). Acc Chem Res 49:2444Google Scholar
  64. 64.
    Baudoin O (2017). Acc Chem Res 50:549Google Scholar
  65. 65.
    Wu X, Neumann H, Beller M (2013). Chem Rev 113:1Google Scholar
  66. 66.
    Matthey J. Price charts. Accessed 24 Apr 2019
  67. 67.
    Hagelüken C (2005) Markets for the catalyst metals platinum, palladium and rhodium. Metall 60(1):31–42. Scholar
  68. 68.
    Hayler JD, Leahy DK, Simmons EM (2019). Organometallics 38:36Google Scholar
  69. 69.
    Prices at the time of writing this were 38$/mmol Pd2dba3(Per Pd); 25$/mmol Pd(OAc)2; 26.7$/mmol XPhos; 146$/mmol BrettPhos; PtBu3 12$/mmol; 6.7$/mmol PCy3Google Scholar
  70. 70.
  71. 71.
    Wang L, Green L, Li Z, Dunn JM, Bu X, Welch CJ, Li C, Wang T, Tu Q, Bekos E, Richardson D, Eckert J, Cui J (2011). Org Process Res Dev 15:1371Google Scholar
  72. 72.
    Jo J, Tu Q, Xiang R, Li G, Zou L, Maloney KM, Ren H, Newman JA, Gong X, Bu X (2019). Organometallics 38:185Google Scholar
  73. 73.
    Miyamoto H, Sakumoto C, Takekoshi E, Maeda Y, Hiramoto N, Itoh T, Kato Y (2015). Org Process Res Dev 19:1054Google Scholar
  74. 74.
    Fors BP, Krattiger P, Strieter E, Buchwald SL (2008). Org Lett 10:3505Google Scholar
  75. 75.
    Melvin PR, Balcells D, Hazari N, Nova A (2015). ACS Catal 5:5596Google Scholar
  76. 76.
    Colcacot TJ (2015) Preface. In: Colacot TJ (ed) New trends in cross-coupling: theory and applications. Royal Society of Chemistry, Cambridge, pp xiii–xixvGoogle Scholar
  77. 77.
    Deddis CR Introduction. Process economics. Chem Eng Chem Process Technol IV:1–3Google Scholar
  78. 78.
    Heinlein RA (1966) The moon is a harsh mistress. Putnam, New YorkGoogle Scholar
  79. 79.
    Colacot T (2012). J Platinum Metals Rev 56:110Google Scholar
  80. 80.
    Chekal BP, Guinness SM, Lillie BM, McLaughlin RW, Palmer CW, Post RJ, Sieser JE, Singer RA, Sluggett GW, Vaidyanathan R, Withbroe GJ (2014). Org Process Res Dev 18:266Google Scholar
  81. 81.
    Netherton MR, Fu GC (2001). Org Lett 3:4295Google Scholar
  82. 82.
    Busacca CA, Cerreta M, Dong Y, Eriksson MC, Farina V, Feng X, Kim J, Lorenz JC, Sarvestani M, Simpson R, Varsolona R, Vitous J, Campbell SJ, Davis MS, Jones P, Norwood D, Qiu F, Beaulieu PL, Duceppe J, Haché B, Brong J, Chiu F, Curtis T, Kelley J, Lo YS, Powner TH (2008). Org Process Res Dev 12:603Google Scholar
  83. 83.
    Mauger C, Mignani G (2005). Adv Synth Catal 347:773Google Scholar
  84. 84.
    Carole WA, Colacot T (2016). J Chem Eur J 22:7686Google Scholar
  85. 85.
    Carole WA, Bradley J, Sarwar M, Colacot T (2015). J Org Lett 17:5472Google Scholar
  86. 86.
    Bedford RB, Bowen JG, Davidson RB, Haddow MF, Seymour-Julen AE, Sparkes HA, Webster RL (2015). Angew Chem Int Ed 54:6591Google Scholar
  87. 87.
    High purity palladium acetate, Pd3(OAC)6, is available from Johnson-Matthey as Pd-111.
  88. 88.
    Wei CS, Davies GHM, Soltani O, Albrecht J, Gao Q, Pathirana C, Hsiao Y, Tummala S, Eastgate MD (2013). Angew Chem Int Ed 52:5822Google Scholar
  89. 89.
    Cong M, Fan Y, Raimundo J, Tang J, Peng L (2014). Org Lett 16:4074Google Scholar
  90. 90.
    Kapdi AR, Whitwood AC, Williamson DC, Lynam JM, Burns MJ, Williams TJ, Reay AJ, Holmes J, Fairlamb IJS (2013). J Am Chem Soc 135:8388Google Scholar
  91. 91.
    Garrett CE, Prasad K (2004). Adv Synth Catal 346:889–900Google Scholar
  92. 92.
    Sawadjoon S, Orthaber A, Sjöberg PJR, Eriksson L, Samec JSM (2014). Organometallics 33:249Google Scholar
  93. 93.
    Janusson E, Zijlstra HS, Nguyen PPT, MacGillivray L, Martelinoa J, McIndoe JS (2017). Chem Commun 53:854Google Scholar
  94. 94.
    Fairlamb IJS, Kapdi AR, Lee AF (2004). Org Lett 6:4435Google Scholar
  95. 95.
    Merritt JM, Buser JY, Campbell AN, Fennell JW, Kallman NJ, Koenig TM, Moursy H, Pietz MA, Scully N, Singh UK (2014). Org Process Res Dev 18:246Google Scholar
  96. 96.
    Zalesskiy SS, Ananikov VP (2012). Organometallics 31:2302Google Scholar
  97. 97.
    Anderson CE, Kirsch SF, Overman LE, Richards CJ, Watson MP (2007). Organic Synth 84:148Google Scholar
  98. 98.
    Young AJ, White MC (2008). J Am Chem Soc 130:14090Google Scholar
  99. 99.
    Grasa GA, Colacot TJ (2007). Org Lett 9:5489Google Scholar
  100. 100.
    Klingensmith LM, Strieter ER, Barder TE, Buchwald SL (2006). Organometallics 25:82Google Scholar
  101. 101.
    Shaughnessy KH (2015) In: Colacot TJ (ed) New trends in cross-coupling: theory and applications. Royal Society of Chemistry, Cambridge, pp 139–154Google Scholar
  102. 102.
    Zim D, Buchwald SL (2003). Org Lett 5:2413–2415Google Scholar
  103. 103.
    Li H, Johansson Seechurn CCC, Colacot TJ (2012) More in depth analysis of the synthesis of these complexes can be found. ACS Catal 2:1147Google Scholar
  104. 104.
    Johansson Seechurn CCC, Colacot TJ (2015) In: Colacot TJ (ed) New trends in cross-coupling: theory and applications. Royal Society of Chemistry, Cambridge, p 95Google Scholar
  105. 105.
    Coombs JR, Fraunhoffer KJ, Simmons ER, Stevens JM, Wisniewski SR, Yu M (2017). J Org Chem 82:7040Google Scholar
  106. 106.
    Albaugh-Robersson P, Katzenellenbogen JA (1982). Tetrahedron Lett 23:723Google Scholar
  107. 107.
    Lu CC, Peters JC (2004). J Am Chem Soc 126:15818Google Scholar
  108. 108.
    Amatore C, Jutand A (2000). Acc Chem Res 33:314Google Scholar
  109. 109.
    Guram AS, King AO, Allen JG, Wang X, Schenkel LB, Chan J, Bunel EE, Faul MM, Larsen RD, Martinelli MJ, Reider PJ (2007). Org Lett 72:5104Google Scholar
  110. 110.
    Guram AS, King AO, Allen JG, Wang X, Schenkel LB, Chan J, Bunel EE, Faul MM, Larsen RD, Martinelli MJ, Reider PJ (2006). Org Lett 8:1787Google Scholar
  111. 111.
    Cooke JWB, Bright R, Coleman MJ, Jenkins KP (2001). Org Process Res Dev 5:383Google Scholar
  112. 112.
    Jacks TE, Belmont DT, Briggs CA, Horne NM, Kanter GD, Karrick GL, Krikke JJ, McCabe RJ, Mustakis JG, Nanninga TN, Risedorph GS, Seamans RE, Skeean R, Winkle DD, Zennie TM (2004). Org Process Res Dev 8:201Google Scholar
  113. 113.
    Moseley JD, Murray PM, Turp ER, Tyler SNG, Burn RT (2012). Tetrahedron 68:6010Google Scholar
  114. 114.
    Murray PM, Bower JF, Cox DK, Galbraith EK, Parker JS, Sweeney JB (2013). Org Process Dev 17:397Google Scholar
  115. 115.
    Serrano JL, García L, Pérez J, Pérez E, García J, Sánchez G, Sehnal P, De Ornellas S, Williams TJ, Fairlamb IJS (2011). Organometallics 30:5095Google Scholar
  116. 116.
    Ji Y, Plata RE, Regens CS, Hay M, Schmidt M, Razler T, Qiu Y, Geng P, Hsiao Y, Rosner T, Eastgate MD, Blackmond DG (2015). J Am Chem Soc 137:13272Google Scholar
  117. 117.
    Trzeciak AM, Ziółkowski JJ (2002). Organometallics 21:132Google Scholar
  118. 118.
    Kamer PCJ, van Leeuwen PWNM, Reek JNH (2001). Acc Chem Res 34:895Google Scholar
  119. 119.
    Colacot TJ, Parisel S (2008) In: Stepnick P (ed) Ferrocenes: ligands, materials and biomolecules. Wiley, West Sussex, pp 117–141Google Scholar
  120. 120.
    Senn HM, Ziegler T (2004). Organometallics 23:2980Google Scholar
  121. 121.
    Yin J, Buchwald SL (2002). J Am Chem Soc 124:6043Google Scholar
  122. 122.
    Schnetz T, Röder M, Romingera F, Hofmann P (2008) Dalton Trans 2238Google Scholar
  123. 123.
    Kawatsura M, Hartwig JF (1999). J Am Chem Soc 121:1473Google Scholar
  124. 124.
    Bellingham R, Borrett G, Bret G, Choudary B, Colclough D, Hayes J, Hayler J, Hodnett N, Ironmonger A, Ochen A, Pascoe D, Richardson J, Vit E, Alexandre F, Caillet C, Amador A, Bot S, Bonaric S, da Costa D, Lioure M, Roland A, Rosinovsky E, Parsy C, Dousson CB (2018). Org Process Res Dev 22:200Google Scholar
  125. 125.
    Hughes DL (2017). Org Process Res Dev 21:1227Google Scholar
  126. 126.
    Hartwig JF, Kawatsura M, Hauck SI, Shaughnessy KH, Alcazar-Roman LM (1999). J Org Chem 64:5575Google Scholar
  127. 127.
    Kruger AW, Rozema MJ, Chu-Kung A, Gandarilla J, Haight AR, Kotecki BJ, Richter SM, Schwartz AM, Wang Z (2009). Org Process Res Dev 13:1419Google Scholar
  128. 128.
    Nicholas PP (1987). J Org Chem 52:5266Google Scholar
  129. 129.
    Littke AF, Fu GC (1998). Angew Chem Int Ed 37:3387Google Scholar
  130. 130.
    Littke AF, Fu GC (1999). J Org Chem 64:10Google Scholar
  131. 131.
    Yoshida T, Otsuka S (1990). Inorg Synth 28:113Google Scholar
  132. 132.
    Norton DM, Mitchell EA, Botros NR, Jessop PG, Baird MC (2009). J Org Chem 74:6674Google Scholar
  133. 133.
    Ogata T, Hartwigm JF (2008). J Am Chem Soc 130:13848Google Scholar
  134. 134.
    Paul F, Patt J, Hartwig JF (1995). Organometallics 14:3030Google Scholar
  135. 135.
    Dai C, Fu GC (2001). J Am Chem Soc 123:2719Google Scholar
  136. 136.
    Morris RJ, Girolami GS (1990). Inorg Chem 29:4167Google Scholar
  137. 137.
    Johnson Matthey PLC. Preparation of a metal complex. US Patent US8772520B2. 12 Jan 2010Google Scholar
  138. 138.
    Li H, Grasa GA, Colacot TJ (2010). Org Lett 12:3332Google Scholar
  139. 139.
    Matsuoka RT, Boros EE, Brown AD, Bullock KM, Canoy WL, Carpenter AJ, Cobb JD, Condon SE, Deschamps NM, Elitzin VI, Erickson G, Fang JM, Igo DH, Joshi BK, Kaldor IW, Mitchell MB, Peckham GE, Reynolds DW, Salmon MC, Sharp MJ, Tabet EA, Toczko JF, Wu LM, Zhou XM (2016). Org Process Res Dev 20:1469–1475Google Scholar
  140. 140.
    Huang Q, Richardson PF, Sach NW, Zhu J, Liu KKC, Smith GL, Bowles DM (2011). Org Process Res Dev 15:556Google Scholar
  141. 141.
    Nonoyama A, Nakai Y, Lee S, Suzuki S, Ando T, Fukuda N, Tanaka H, Takahashi K (2019) Org Proc Res Dev. In PressGoogle Scholar
  142. 142.
    Zheng Q, Liu Y, Chen Q, Hu M, Helmy R, Sherer EC, Welch CJ, Chen H (2015). J Am Chem Soc 137:14035Google Scholar
  143. 143.
    Barrios-Landeros F, Carrow BP, Hartwig JF (2009). J Am Chem Soc 131:8141Google Scholar
  144. 144.
    Ingoglia BT, Buchwald SL (2017). Org Lett 19:2853Google Scholar
  145. 145.
    Anjali BA, Suresh CH (2017). ACS Omega 2:4196Google Scholar
  146. 146.
    Biscoe MR, Fors BP, Buchwald SLJ (2008). Am Chem Soc 130:6686Google Scholar
  147. 147.
    DeAngelis AJ, Gildner PG, Chow R, Colacot TJ (2015). J Org Chem 80:6794Google Scholar
  148. 148.
    Vilar R, Michael D, Mingos P, Cardin CJ (1996) J Chem Soc Dalton Trans 4313Google Scholar
  149. 149.
    Beller M, Fischer H, Herrmann WA, Öfele K, Brossmer C (1995). Angew Chem Int Ed 34:1848Google Scholar
  150. 150.
    Schnyder A, Indolese AF, Studer M, Blaser H (2002). Angew Chem Int Ed 41:3668Google Scholar
  151. 151.
    Bruno NC, Niljianskul N, Buchwald SL (2014). J Org Chem 79:4161Google Scholar
  152. 152.
    Krska SW, DiRocco DA, Dreher SD, Shevlin M (2017). Acc Chem Res 50:2976Google Scholar
  153. 153.
    PIQUR Therapeutics AG; Universitaet Basel; Conformationally restricted P13K and mTOR inhibitors. US Patent US9556203B2. 31 Jan 2017Google Scholar
  154. 154.
    Stumpf A, McClory A, Yajima H, Segraves N, Angelaud R, Gosselin F (2016). Org Process Res Dev 20:751Google Scholar
  155. 155.
    Heffron TP, Ndubaku CO, Salphati L, Alicke B, Cheong J, Drobnick J, Edgar K, Gould SE, Lee LB, Lesnick JD, Lewis C, Nonomiya J, Pang J, Plise EG, Sideris S, Wallin J, Wang L, Zhang X, Olivero AG (2016). ACS Med Chem Lett 7:351Google Scholar
  156. 156.
    Heffron TP, McClory A, Stumpf A (2016) Comprehensive accounts of pharmaceutical research and development: from discovery to late-stage process development volume 1, pp 147–173Google Scholar
  157. 157.
    Lennox AJJ, Lloyd-Jones GC (2014). Chem Soc Rev 43:412Google Scholar
  158. 158.
    Sun J, Perfetti MT, Santos WL (2011). J Org Chem 76:3571Google Scholar
  159. 159.
    Molander GA, Trice SLJ, Kennedy SM (2012). J Org Chem 77:8678Google Scholar
  160. 160.
    Smith AC, Kung DW, Shavnya A, Brandt TA, Dent PA, Genung NE, Cabral S, Panteleev J, Herr M, Yip KN, Aspnes GE, Conn EL, Dowling MS, Edmonds DJ, Edmonds ID, Fernando DP, Herrinton∥ PM, Keene NF, Lavergne SY, Li Q, Polivkova J, Rose CR, Thuma BA, Vetelino MG, Wang G, Weaver JD, Widlicka DW, Wiglesworth KEP, Xiao J, Zahn T, Zhang Y (2018). Org Process Res Dev 22:681Google Scholar
  161. 161.
    Hansen MM, Jolly RA, Linder RJ (2015). Org Process Res Dev 19:1507Google Scholar
  162. 162.
    Gurung SR, Mitchell C, Huang J, Jonas M, Strawser JD, Daia E, Hardy A, O’Brien E, Hicks F, Papageorgiou CD (2017). Org Process Res Dev 21:65Google Scholar
  163. 163.
    Usutani H, Nihei T, Papageorgiou CD, Cork DG (2017). Org Process Res Dev 21:669Google Scholar
  164. 164.
    Viciu-Fernandez O, Stevens ED, Nolan SP (2002). Organometallics 21:5470Google Scholar
  165. 165.
    Galardon E, Ramdeehul S, Brown JM, Cowley A, Hii KK, Jutand A (2002). Angew Chem Int Ed 41:1760Google Scholar
  166. 166.
    Viciu MS, Navarro O, Germaneau RF, Kelly RA, Sommer W, Marion N, Stevens ED, Cavallo L, Nolan SP (2004). Organometallics 23:1629Google Scholar
  167. 167.
    Chartoire A, Lesieur M, Slawin AMZ, Nolan SP, Cazin CSJ (2011). Organometallics 30:4432–4436Google Scholar
  168. 168.
    Marion N, Navarro O, Mei J, Stevens ED, Scott NM, Nolan SP (2006). J Am Chem Soc 128:4101Google Scholar
  169. 169.
    Takeda Y, Ikeda Y, Kuroda A, Tanaka S, Minakata S (2014). J Am Chem Soc 136:8544Google Scholar
  170. 170.
    Hruszkewycz DP, Balcells D, Guard LM, Hazari N, Tilset M (2014). J Am Chem Soc 136:7300Google Scholar
  171. 171.
    Linghu X, Wong N, Iding H, Jost V, Zhang H, Koenig SG, Sowell CG, Gosselin F (2017). Org Process Res Dev 21:387Google Scholar
  172. 172.
    Linghu X, Wong N, Jost V, Fantasia S, Sowell CG, Gosselin F (2017). Org Process Res Dev 21:1320Google Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Johnson MattheyWest DeptfordUSA

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