The atroposelective synthesis of PINAP ligands has been accomplished via a palladium‐catalyzed C−P coupling process through dynamic kinetic asymmetric transformation. These catalytic conditions allow access to a wide variety of alkoxy‐ and benzyloxy‐substituted PINAP ligands in high enantiomeric excess. The methods described in this communication afford valuable P,N ligands in good yields and high enantioselectivity using low catalyst loading

Bhat, Vikram

Han, Seo-Jung

Stoltz, Brian M.

Virgil, Scott C.

Caltech Authors - Main

Title: Atroposelective Synthesis of PINAP via Dynamic Kinetic
Asymmetric Transformation
Authors: Seojung Han, Vikram Bhat, Brian Stoltz, and Scott Virgil
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801248
Link to VoR: http://dx.doi.org/10.1002/adsc.201801248
 1 
 COMMUNICATION 
DOI: 10.1002/adsc.201((will be filled in by the editorial staff)) 
Atroposelective Synthesis of PINAP via Dynamic Kinetic 
Asymmetric Transformation 
Seo-Jung Han,a,b Vikram Bhat,a,c Brian M. Stoltz,*a and Scott C. Virgil*a 
a The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and 
Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 101-20, Pasadena, 
California 91125, United States 
 E-mail: stoltz@caltech.edu and svirgil@caltech.edu  
b Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), 5, Hwarangro 14-gil, 
Seongbuk-gu, Seoul, 02792, Republic of Korea 
c Abbvie, Inc., 1 N Waukegan Road, North Chicago, IL 60064, United States 
Received: ((will be filled in by the editorial staff)) 
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please 
delete if not appropriate)) 
Abstract. The atroposelective synthesis of PINAP ligands 
has been accomplished via a palladium-catalyzed C–P 
coupling process through dynamic kinetic asymmetric 
transformation.  These catalytic conditions allow access to a 
wide variety of alkoxy- and benzyloxy-substituted PINAP 
ligands in high enantiomeric excess.  The methods 
described in this communication afford valuable P,N 
ligands in good yields and high enantioselectivity using low 
catalyst loading. 
Keywords: PINAP; Dynamic kinetic asymmetric 
transformation; Atroposelective synthesis; P,N ligands 
 
The unique properties of the axially chiral P,N 
ligand QUINAP (1) have been employed widely for 
various transition metal catalyzed asymmetric 
reactions.[1]  Thus, approaches to the synthesis of  
QUINAP ligands in high enantiomeric purity have 
been developed.[2,3]  In 2013, our laboratories 
explored the palladium-catalyzed atroposelective 
synthesis of QUINAP and its derivatives via kinetic 
resolution and dynamic kinetic asymmetric 
transformation.[4]  With a robust method for the 
synthesis of chiral QUINAP in hand, we turned our 
attention to the architecturally related PINAP ligands 
(2).[5]  PINAP ligands (2a and 2b), which possess 
analogous ligation reactivity to QUINAP, were first 
developed by the Carreira group in 2004.[6]  Carreira 
and co-workers separated the two atropoisomeric     
diastereomers     through      column  
Figure 1. QUINAP (1) and PINAP (2) 
chromatography by preparing chiral ether- or amine-
substituted PINAP scaffolds.  Herein, we disclose 
synthetic methods for accessing enantiomerically 
enriched PINAP ligands via dynamic kinetic 
asymmetric transformation (2a, 2c).   
Table 1. Scope of Dynamic Kinetic Asymmetric 
Transformation Under Initial Standard Conditions 
a Reactions performed with 1.0 equiv of triflate 3, 4.0 equiv of DMAP, 
3.0 mol % of Pd[(o-tol)3P]2, 4.5 mol % of (S, RFc)-Josiphos, 1.05 equiv of 
N
N
OTf
OR
Pd[(o-tol)3P]2 (3.0 mol %)
(S, RFc)-Josiphos (4.5 mol %)
Ph2PH, DMAP 
dioxane, 80 °C
3 4
N
N
PPh2
OR
Fe
PCy2
Cy2P
(S, RFc)-Josiphos
4a
N
N
PPh2
OMe
4d
N
N
PPh2
O
4g
N
N
PPh2
O
4f
N
N
PPh2
O
4e
N
N
PPh2
O
4b
N
N
PPh2
OEt
4c
N
N
PPh2
O
90% yieldb, 82% eec 80% yieldb, 75% eec
70% yieldb, 60% eec63% yieldb, 82% eec
t-Bu
61% yieldb, 88% eec
48% yieldb, 71% eec 71% yieldb, 86% eec
10.1002/adsc.201801248
Ac
ce
pt
ed
 M
an
us
cr
ip
t
Advanced Synthesis & Catalysis
This article is protected by copyright. All rights reserved.
 2 
Ph2PH (1.0 M in dioxane) at 0.20 M in dioxane at 80 °C in a glovebox.  
Ph2PH (1.0 M in dioxane) was added over 4 h. b All yields are isolated 
yields.  c Determined by chiral SFC analysis.  
Our initial attempts to apply the standard QUINAP 
dynamic kinetic asymmetric transformation 
conditions,[4] 3.0 mol % of Pd[(o-tol)3P]2  and 4.5 
mol % of (S, RFc)-Josiphos at 80 °C, to  aryl  triflate 3 
afforded various  alkyl-  or  benzyl-substituted  
PINAP  ligands (Table 1).  Asymmetric C–P 
couplings via dynamic kinetic asymmetric 
transformation on substrates incorporating methoxy, 
ethoxy, and isopropoxy groups furnished the 
corresponding PINAP ligands in good yields and 
selectivities (4a, 4b, 4c).  Cyclohexyl, 3,3-dimethyl-
1-butyl, and homoallyl ether groups were also well 
tolerated under the reaction conditions to give the 
desired products. (4d, 4e, 4f).  Additionally, 3,5-
dimethyl benzyloxy-substituted PINAP was obtained 
in good yield and moderate selectivity (4g).  Although 
these initial results were exciting, it was clear that 
additional optimization was needed to improve the 
enantioselectivities in the synthesis of these PINAP 
ligands.  
In order to allow more time for the isomerization of 
the presumed arylpalladium complex before its 
subsequent phosphination, diphenylphosphine (1.0 M 
solution in dioxane) was added slowly.[7]  In addition, 
we used pre-stirred 1.0 mol % of Pd[(o-tol)3P]2 and 
1.5 mol % of (S, RFc)-Josiphos solutions in dioxane.  
Interestingly, improved enantioselectivity was 
observed with reduced palladium and Josiphos ligand 
loadings (1.0 mol % and 1.5 mol %, respectively) 
(Table 2, entries 1 and 2).  We were pleased to find 
that higher enantioselectivities were obtained at lower 
temperatures (Table 2, entries 2–4).  However, the 
conversion rate was dramatically diminished at 50 °C 
(Table 2, entry 5). 
Table 2. Optimization of Reaction Parameters 
a Reactions performed with 1.0 equiv of 3a, 4.0 equiv of DMAP, 1.0 
mol % of Pd[(o-tol)3P]2, 1.5 mol % of (S, RFc)-Josiphos, 1.05 equiv of 
Ph2PH (1.0 M in dioxane) at 0.20 M in dioxane in a glovebox.  Pd[(o-
tol)3P]2 and (S, RFc)-Josiphos in dioxane were pre-stirred before use.  
Ph2PH (1.0 M in dioxane) was added over 8 h.  b All yields are isolated 
yields.  c Determined by chiral SFC analysis.  d ~50% conversion. 
With the optimized conditions in hand, we 
investigated the substrate scope of the reaction (Table 
3).  Several alkoxy- and benzyloxy-substituted 
PINAP ligands were furnished in improved 
enantioselectivities under the optimized conditions 
(4a–4h, 57–80% yields and 82–96% ee).  Even 
PINAP 4g, which had been our worst example under 
our initial conditions, could now be prepared in 60% 
yield and 94% ee.  Applying our optimized conditions 
to a (R)-phenylethoxy-substituted substrate, which 
was previously prepared by the Carreira group by 
chromatographic separation, generated the 
corresponding PINAP product in 95% de (4i).  
Interestingly, diastereomeric PINAP 2a was produced 
by our method with lower selectivity using the (R, 
SFc)-Josiphos ligand indicating some balance between 
substituent and catalyst in the process (e.g., 
mismatched pair).  Thankfully, nearly enantiopure 
PINAP 2a was obtained after recrystallization.[8] 
Unfortunately, in the case of (R)--phenethylamine 
substituted PINAP, only moderate selectivity was 
observed (4j).  Additionally, application of our 
conditions   to    the   reaction   of   triflate     3a     
with  
Table 3. Scope of Dynamic Kinetic Resolution Under 
Optimized Conditions 
N
N
OTf
OMe
Pd[(o-tol)3P]2
(S, RFc)-Josiphos 
Ph2PH, DMAP 
dioxane
3a 4a
N
N
PPh2
OMe
Fe
PCy2
Cy2P
(S, RFc)-Josiphos
entry T (°C)
3 70
4 60
5 50
1 80
2 80
Pd[(o-tol)3P]2 yield (%)
b ee (%)(S, RFc)-Josiphos
3.0 mol %
1.0 mol %
1.0 mol %
1.0 mol %
1.0 mol %
4.5 mol %
1.5 mol %
1.5 mol %
1.5 mol %
1.5 mol %
90
95
75
80
–d
82c
88c
92c
96c
94c
10.1002/adsc.201801248
Ac
ce
pt
ed
 M
an
us
cr
ip
t
Advanced Synthesis & Catalysis
This article is protected by copyright. All rights reserved.
 3 
 a Reactions performed with 1.0 equiv of 3, 4.0 equiv of DMAP, 1.0 
mol % of Pd[(o-tol)3P]2, 1.5 mol % of (S, RFc)-Josiphos, 1.05 equiv of 
Ph2PH (1.0 M in dioxane) at 0.20 M in dioxane at 60 °C in a glovebox.  
Pd[(o-tol)3P]2 and (S, RFc)-Josiphos in dioxane were pre-stirred before use.  
Ph2PH (1.0 M in dioxane) was added over 8 h.  b All yields are isolated 
yields.  c Determined by chiral SFC analysis.  d Determined by chiral SFC 
analysis; SFC conditions: 40% IPA, 2.5 mL/min, Chiralpak OD-H column, 
tR (min): major = 2.26, minor = 3.12.  e Determined by chiral HPLC.  f (R, 
SFc)-Josiphos was used.  g Determined by 
1H NMR. h. The absolute 
stereochemistry of the PINAP ligands were assigned based on the 
stereochemical outcome of the known PINAP 4i, 2a, and 4j. 
 
diphenylphosphine oxide or (p-CF3-C6H4)2PH proved 
unsuccessful, and only low yield and selectivities 
were observed.[9,10] 
We applied PINAP ligand 4a (96% ee) to two 
different reactions (Scheme 1).  Copper catalyzed 
asymmetric phenylacetylene addition to isoquinoline 
iminium 5 with PINAP ligand 4a afforded 
propargylamine 6 in 98% yield and 96% ee (Scheme 
1a).[1l,11] In addition, rhodium-catalyzed 
enantioselective diboration and oxidation of trans--
methylstyrene 7 with PINAP 4a produced diol 8 in 
71% yield and 88% ee (Scheme 1b).[1e,j,12]  The 
enantioselectivities and yields with PINAP ligand 4a 
are parallel to those with QUINAP 1. 
Scheme 1. Applications of PINAP 4a in Catalytic 
Asymmetric Transformations[13] 
 
In conclusion, the atroposelective synthesis of 
various achiral alkyl- or benzyloxy-substituted PINAP 
ligands via dynamic kinetic asymmetric 
transformation has been developed.  The asymmetric 
PINAP ligands formed in this communication are 
envisioned to be useful in several important 
asymmetric reactions.  
Experimental Section 
(This reaction was performed in a nitrogen-filled 
glovebox.) Pd[(o-tol)3P]2 (10.8 mg, 0.0151 mmol) and (S, 
RFc)-Josiphos (13.7 mg, 0.0226 mmol) in dioxane (0.302 
mL) were pre-stirred in a vial until all the solids were 
dissolved.  To a solution of triflates 3 (0.211 mmol, 1.00 
equiv) in dioxane (1.06 mL) was added DMAP (0.844 
mmol, 4.00 equiv) and pre-stirred Pd[(o-tol)3P]2 and (S, 
RFc)-Josiphos (0.05 M in dioxane; 0.00211 mmol, 0.01 
equiv) at 23 °C.  The mixture was placed in a reaction well 
preheated to 60 °C.  A solution of Ph2PH (1.00 M in 
dioxane; 0.317 mmol, 1.50 equiv) was added to the 
reaction mixture in 20 uL portions every 30 minutes 
manually.  After completion of the addition (8 hours), the 
reaction was stirred for further 7 hours at which point 
complete consumption of the starting material was 
observed.  The reaction was cooled, removed from the 
glovebox and dilulted with EtOAc (1.50 mL) and water 
(2.00 mL).  The aqueous phase was extracted with EtOAc 
(3 x 1.50 mL).  The combined organic phases were washed 
with brine, dried with MgSO4 and concentrated.  The crude 
material was purified by flash column chromatography on 
silica gel to afford the corresponding PINAP 4. 
Acknowledgements 
The authors wish to thank NIH-NIGMS (R01GM080269), Amgen, 
the Gordon and Betty Moore Foundation, the Caltech Center for 
Catalysis and Chemical Synthesis, and Caltech for financial 
support.  S.-J.H. thanks the Fulbright program (Foreign Student 
Program, No. 15111120), the Ilju Foundation of Education & 
Culture (Pre-doctoral Research Fellowship), and the KIST 
institutional program (2E28570, 2E28010) for financial support.  
References 
[1] a) H. Doucet, E. Fernandez, T. P. Layzell, J. M. Brown,    
Chem. Eur. J. 1999, 5, 1320–1330; b) J. W. Faller, B. J. 
Grimmond, Organometallics 2001, 20, 2454–2458; c) 
K. Maeda, J. M. Brown, Chem. Commun. 2002, 310–
311; d) N. Gommermann, C. Koradin, K. Polborn, P. 
Knochel, Angew. Chem. 2003, 115, 5941–5944; Angew. 
N
N
OTf
XR
Pd[(o-tol)3P]2 (1.0 mol %)
(S, RFc)-Josiphos (1.5 mol %)
Ph2PH, DMAP 
dioxane, 60 °C
3 4
N
N
PPh2
XR
Fe
PCy2
Cy2P
(S, RFc)-Josiphos
4a
N
N
PPh2
OMe
80% yieldb, 96% eec
4b
N
N
PPh2
OEt
73% yieldb, 94% eec
4c
N
N
PPh2
O
70% yieldb, 82% eec
4d
N
N
PPh2
O
67% yieldb, 95% eec
4e
N
N
PPh2
O
t-Bu
57% yieldb, 95% eec
4f
N
N
PPh2
O
67% yieldb, 94% eec
4g
N
N
PPh2
O
60% yieldb, 94% eec
N
N
PPh2
O
4h
72% yieldb, 94% eec
4i
N
N
PPh2
O Ph
65% yieldb, 95% ded,g
2af
N
N
PPh2
O
71% yieldb, 88% dee,g
(57% yield, >99% deg
after recrystallization)
Ph
4j
N
N
PPh2
HN Ph
79% yieldb, 60% deg
X = O, NH X = O, NH
10.1002/adsc.201801248
Ac
ce
pt
ed
 M
an
us
cr
ip
t
Advanced Synthesis & Catalysis
This article is protected by copyright. All rights reserved.
 4 
Chem. Int. Ed. 2003, 42, 5763–5766; e) J. B. Morgan, S. 
P. Miller, J. P. Morken, J. Am. Chem. Soc. 2003, 125, 
8702–8703; f) C. Chen, X. Li, S. L. Schreiber, J. Am. 
Chem. Soc. 2003, 125, 10174–10175; g) E. Daura-Oller, 
A. M. Segarra, J. M. Poblet, C. Claver, E. Fernández, C. 
Bo, J. Org. Chem. 2004, 69, 2669–2680; h) A. Black, J. 
M. Brown, C. Pichon, Chem. Commun. 2005, 5284–
5286; i) N. Gommermann, P. Knochel, Chem. 
Commun., 2005, 4175–4177, j) S. Trudeau, J. B. 
Morgan, M. Shrestha, J. P. Morken, J. Org. Chem. 2005, 
70, 9538–9544; k) N. Gommermann, P. Knochel, 
Chem.–Eur. J. 2006, 12, 4380–4392; l) A. M. Taylor, S. 
L. Schreiber, Org. Lett. 2006, 8, 143–146; m) X. Li, L. 
Kong, Y. Gao, X. Wang, Tetrahedron Lett. 2007, 48, 
3915–3917; n) T. Miura, M. Yamauchi, A. Kosaka, M. 
Murakami, Angew. Chem. 2010, 122, 5075–5077; 
Angew. Chem. Int. Ed. 2010, 49, 4955–4957; o) A. D. 
Lim, J. A. Codelli, S. E. Reisman, Chem. Sci. 2013, 4, 
650–654; p) E. Fernández, P. J. Guiry, K. P. T. Connole, 
J. M. Brown, J. Org. Chem. 2014, 79, 5391–5400; q) P. 
Ramírez-López, A. Ros, A. Romero-Arenas, J. Iglesias-
Sigüenza, R. Fernández, J. M. Lassaletta, J. Am. Chem. 
Soc. 2016, 138, 12053–12056; r) V. Hornillos, A. Ros, 
P. Ramírez-López, J. Iglesias-Sigüenza, R. Fernández, J. 
M. Lassaletta, Chem. Commun., 2016, 52, 14121–
14124; s) V.  Bhat, E. R. Welin, X. Guo, B. M. Stoltz, 
Chem. Rev. 2017, 117, 4528–4561 
[2] a) N. W. Alcock, J. M. Brown, D. I. Hulmes, 
Tetrahedron: Asymmetry 1993, 4, 743–756; b) C. W. 
Lim, O. Tissot, A. Mattison, M. W. Hooper, J. M. 
Brown, A. R. Cowley, D. I. Hulmes, A. J. Blacker, Org. 
Process Res. Dev. 2003, 7, 379–384; c) T. Thaler, F. 
Geittner, P. Knochel, Synlett 2007, 2655–2658; d) J. 
Clayden, S. P. Fletcher, J. J. W. McDouall, S. J. M. 
Rowbottom, J. Am. Chem. Soc. 2009, 131, 5331–5343; 
e) P. Ramírez-López, A. Ros, B. Estepa, R. Fernández, 
B. Fiser, E. Gómez-Bengoa, J. M. Lassaletta, ACS 
Catal. 2016, 6, 3955–3964. 
[3] For selective recent examples on the atroposelective 
syntheses, see: a) S.-C. Zheng, S. Wu, Q. Zhou, L. W. 
Chung, L. Ye, B. Tan, Nat. Commun. 2017, 8, 15238. 
b) Q.-J. Yao, S. Zhang, B.-B. Zhan, B.-F. Shi, Angew. 
Chem., Int. Ed. 2017, 56, 6617–6621. c) L. Zhang, J. 
Zhang, J. Ma, D.-J. Cheng, B. Tan, J. Am. Chem. Soc. 
2017, 139, 1714–1717. d) Y.-B. Wang, S.-C. Zheng, 
Y.-M. Hu, B. Tan, Nat. Commun. 2017, 8, 15489. e) J. 
D. Jolliffe, R. J. Armstrong, M. D. Smith, Nat. Chem. 
2017, 9, 558–562. f) J. Zheng, W.-J. Cui, C. Zheng, S.-
L. You, J. Am. Chem. Soc. 2016, 138, 5242–5245. g) C. 
Yu, H. Huang, X. Li, Y. Zhang, W. Wang, J. Am. Chem. 
Soc. 2016, 138, 6952–6959. h) R. Miyaji, K. Asano, S. 
Matsubara, J. Am. Chem. Soc. 2015, 137, 6766–6769. i) 
A. Berthelot-Bréhier, A. Panossian, F. Colobert, F. R. 
Leroux, Org. Chem. Front., 2015, 2, 634–644.  
[4] V. Bhat, S. Wang, B. M. Stoltz, S. C. Virgil, J. Am. 
Chem. Soc. 2013, 135, 16829–16832. 
[5] For selected recent works on asymmetric reactions with 
PINAP ligands, see: a) X. Ma, Z. Gu, RSC Adv., 2014, 
4, 36241–36244; b) S. Zhou, R. Tong, Org. Lett. 2017, 
19, 1594–1597; c) W. Fan, W. Yuan, S. Ma, Nat. 
Commun. 2014, 5, 3884; d) K. Wolosewicz, M. 
Michalak, J. Adamek, B. Furman, Eur. J. Org. Chem. 
2016, 12, 2212–2219. 
[6] a) T. F. Knöpfel, P. Aschwanden, T. Ichikawa, T. 
Watanabe, E. M. Carreira, Angew. Chem. 2004, 116, 
6097–6099; Angew. Chem., Int. Ed. 2004, 43, 5971–
5973; b) S. Fujimori, T. F. Knöpfel, P. Zarotti, T. 
Ichikawa, D. Boyall, E. M. Carreira, Bull. Chem. Soc. 
Jpn. 2007, 80, 1635–1657; c) P. Zarotti, T. F. Knöpfel, 
P. Aschwanden, E. M. Carreira, ACS Catal., 2012, 2, 
1232–1234.  
[7] See Ref. 4 for a plausible mechanism of this dynamic 
kinetic asymmetric transformation. 
[8] The crystal was obtained from a gram scale reaction.  
See supporting information for details. 
[9] Attempts to produce PINAP derivatives with 
diphenylphosphine oxide and (p-CF3-C6H4)2PH in high 
enantioselectivities under our dynamic kinetic 
asymmetric transformation conditions were 
unsuccessful.  
 
 [10] To demonstrate the scope of our methodology, the 
enantioselective synthesis of Quinazolinap from triflate 
10 was attempted, but our reaction conditions led to 
poor conversion.  Moreover, treatment of triflate 12 with 
the optimized conditions for PINAP provided the 
QUINAP ligand in diminished selectivity compared to 
that with the original reaction conditions4. 
 
[11] Determined by chiral HPLC analysis: conditions: 10% 
IPA 45 min, AD column, tR: (min): minor = 10.5 min, 
major = 18.2 min.  All the other spectra data were 
identical to the reported data. (ref. 1l) 
N
N
OTf
OMe
Pd[(o-tol)3P]2
(S, RFc)-Josiphos 
Ar2PH, DMAP 
dioxane
3a 9
N
N
PAr2
OMe
Fe
PCy2
Cy2P
(S, RFc)-Josiphos
entry T (°C)
3 70
1 60
2 60
ee (%)
–b
–c
38d
Ar2PH
diphenylphosphine oxide
(p-CF3-C6H4)2PH
(p-CF3-C6H4)2PH
(p-CF3-C6H4)2PH4 80 50d
a Reactions performed with 1.0 equiv of 3a, 4.0 equiv of DMAP, 1.0 mol % of Pd[(o-tol)3P]2, 
1.5 mol % of (S, RFc)-Josiphos, 1.05 equiv of Ar2PH (1.0 M in dioxane) at 0.20 M in dioxane in a 
glovebox.  Ar2PH (1.0 M in dioxane) was added over 8 h.  
b No reaction.  c ~50% conversion. d  
Determined by chiral SFC analysis; SFC conditions: 35% IPA, 2.5 mL/min, Chiralpak IC 
column, tR (min): major = 3.06, minor = 3.98.
O
O
10.1002/adsc.201801248
Ac
ce
pt
ed
 M
an
us
cr
ip
t
Advanced Synthesis & Catalysis
This article is protected by copyright. All rights reserved.
 5 
[12] Determined by chiral SFC analysis: conditions: 20% 
MeOH, 2.5 mL/min, AD-H column, tR (min): major = 
2.46 min, minor = 2.92 min; []D25 +38.6 (c 0.19, 
CHCl3) 
[13] 96% ee (R)-PINAP 4a was used for both applications. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.1002/adsc.201801248
Ac
ce
pt
ed
 M
an
us
cr
ip
t
Advanced Synthesis & Catalysis
This article is protected by copyright. All rights reserved.
 6 
COMMUNICATION    
Atroposelective Synthesis of PINAP via Dynamic 
Kinetic Asymmetric Transformation 
 
 
 
Adv. Synth. Catal. Year, Volume, Page – Page 
Seo-Jung Han, Vikram Bhat, Brian M. Stoltz,* and 
Scott C. Virgil* 
 
 
N
N
OTf
OR
Pd[(o-tol)3P]2 (1.0 mol %)
(S, RFc)-Josiphos (1.5 mol %)
Ph2PH, DMAP 
dioxane, 60 °C
N
N
PPh2
OR
Fe
PCy2
Cy2P
(S, RFc)-Josiphos
57–80% yield, 82–96% ee
10.1002/adsc.201801248
Ac
ce
pt
ed
 M
an
us
cr
ip
t
Advanced Synthesis & Catalysis
This article is protected by copyright. All rights reserved.


Atroposelective Synthesis of PINAP via Dynamic Kinetic Asymmetric Transformation

https://authors.library.caltech.edu/90863/1/Han_et_al-2018-Advanced_Synthesis_%2526_Catalysis.pdf

Atroposelective Synthesis of PINAP via Dynamic Kinetic Asymmetric Transformation

Abstract

Similar works

Full text

Available Versions

Caltech Authors - Main