Site-Selective and Stereoselective trans-Hydroboration of 1,3-Enynes Catalyzed by 1,4-Azaborine-Based Phosphine-Pd Complex

Article abstract of DOI:10.1021/jacs.6b09759

A concise synthesis of monobenzofused 1,4-azaborine phosphine ligands (Senphos) is described. These Senphos ligands uniquely support Pd-catalyzed trans-selective hydroboration of terminal and internal 1,3-enynes to furnish corresponding dienylboronates in

Full text of DOI:10.1021/jacs.6b09759

Subscriber access provided by TUFTS UNIV
Communication
Site- and Stereo-selective trans-Hydroboration of 1,3-Enynes
Catalyzed by 1,4-Azaborine-Based Phosphine-Pd Complex
Senmiao Xu, Yuanzhe Zhang, Bo Li, and Shih-Yuan Liu
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b09759 • Publication Date (Web): 24 Oct 2016
Downloaded from http://pubs.acs.org on October 24, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
Site- and Stereo-selective trans-Hydroboration of 1,3-
Enynes Catalyzed by 1,4-Azaborine-Based Phosphine-Pd
Complex
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Senmiao Xu,§ Yuanzhe Zhang, Bo Li, Shih-Yuan Liu*
Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467-3860, United States
Supporting Information Placeholder
Scheme 1. An application of BN/CC isosterism in catalysis
ABSTRACT: A concise synthesis of monobenzofused 1,4-azaborine
phosphine ligands (Senphos) is described. These Senphos ligands
uniquely support Pd-catalyzed trans-selective hydroboration of termi-
nal and internal 1,3-enynes to furnish corresponding dienylboronates
in high efficiency and diastereoselectivity. X-ray structural analysis of
the Senphos-Pd(0) complex reveals a κ2-P-η2-BC coordination mode,
and this isolated complex has been shown to serve as a competent
catalyst for the trans-hydroboration reaction. This work demonstrates
that the expanded chemical space provided by the BN/CC isosterism
approach translates into the functional space in the context of stereose-
lective catalytic transformations.
1,4-azaborine ligand
κ2,η2-BC coordination
trans-hydroboration
1,4-hydroboration
of a 1,3-enyne
of a 1,3-enyne
Me
N
Me
N
Me
N
H
(3)
B
C
[Pt]
Me
Me
B
B
Pt
PPh2
PPh2
N
N
vs.
Me
B (or L1)
C
A
nal alkyne proton due to the operating reaction mechanisms. Metal
vinylidene species have been proposed for the Miyaura10 and Leitner11
catalysts whereas the Chirik system involves a Co-alkynyl12 intermedi-
ate. Thus, internal enynes would not be suitable substrates for these
systems. Lee and Yun reported very recently a Copper(I)−thiophene-
2-carboxylate/DPEphos catalyzed trans-hydroboration of terminal
aryl-alkynes in which the terminal alkyne proton does not undergo a
migration that is observed in the Miyaura, Leitner, and Chirik sys-
tems.13 To the best of our knowledge, the only metal-catalyzed system
that can achieve the trans-hydroboration of internal alkynes is the
[Cp*Ru(MeCN)3]PF6 system by Fürstner.14 This system works par-
ticularly well with symmetrical internal alkynes, and enynes have been
pointed out as a problematic substrate for Fürstner’s Ru catalyst.
BN/CC isosterism, i.e., the replacement of a CC bond unit with the
isoelectronic and isosteric BN bond unit, has recently emerged as a
viable strategy to increase the structural diversity of organic molecules.1
While early applications have appeared in the area of materials science2
and biomedical research,3 efforts taking advantage of expanded chemi-
cal space provided by BN/CC isosterism in ligand-supported catalysis
for organic synthesis have lagged behind.4-6 This is surprising in view of
tremendous opportunities for achieving new reactivity and selectivity
in catalytic transformations that the electronic tuning through BN/CC
isosterism could potentially provide. In a recent example, we disclosed
that the 1,4-azaborine-based pyridine ligand A (Scheme 1) exhibits a
κ2-η2-BC coordination with group 10 transition metals and that the
phosphine derivative B in conjunction with Pd could uniquely catalyze
the hydroboration of a terminal enyne in a trans-selective fashion.7 In
contrast to B, the corresponding carbonaceous phosphine ligand
isostere C behaves more similarly to a monodentate phosphine such as
PPh3 in terms of hydroboration selectivity and yield, producing prefer-
entially allenes via 1,4-hydroboration; bisphosphine ligands such as
1,2-bis(diphenylphosphino)ethane (dppe) furnish syn-hydroboration
products exclusively.8 Despite this promising preliminary result, our
trans-hydroboration reaction still needed optimization with regard to
yield and selectivity. More importantly, we wondered whether we
could develop a trans-hydroboration protocol for internal enynes, a
substrate class that is considered significantly more challenging (vide
infra).
Scheme 2. Transition-metal catalyzed trans-selective hydrobo-
ration of alkynes
previous work:
trans-hydroboration of terminal alkynes
HB(pin), HBCat,
or HB(dan)
2000, Norio Miyaura
H
R
H
2012, Walter Leitner
2015, Paul Chirik
2016, Jaesok Yun
R
H
Ir, Rh, Ru, Co, Cu
B(pin)
or B(dan)
trans-hydroboration of internal alkynes
H
R
R
HB(pin)
2012, Alois Fürstner
R
R
Cp*Ru(CH3CN)3PF6
B(pin)
this work:
trans-hydroboration of both terminal and internal enynes
H
R3
site-selective
HBCat
R3
stereo-selective
broad substrate scope
scalable
R1
R1
L/Pd(0)
then pinacol
R2 B(pin)
R2
To date, only a handful of metal-catalyzed systems have been
demonstrated to achieve trans-hydroboration of alkynes.9 Miyaura
reported the first example in 2000 using Ir or Rh catalysts (Scheme
2).10 In 2012, Leitner showed that a Ru/PNP pincer complex can pro-
duce Z-vinylboronates via trans-hydroboration of alkynes with H-
Bpin,11 and Chirik introduced a Co-based system in 2015.12 What these
systems have in common is that they require the presence of the termi-
In this communication, we disclose a Pd-catalyzed trans-selective
hydroboration of both terminal and internal 1,3-enynes with high site-
and stereo-selectivity that is supported by 1,4-azaborine-based phos-
phine ligands. Key to the successful development of this reaction is a
new, concise synthesis of monobenzofused 1,4-azaborine phosphines
(Senphos), which we report here as well.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
Our original synthesis of Senphos-type ligands via ring-closing me-
smaller substituents (Table 1, enty 4 vs. entries 1-3). Switching the
tathesis7 was unfortunately not amenable to scale-up15 and ready modi-
fication of the C(3) position, which we believe could play an important
role due to its proximity to the catalytically active Pd metal. This syn-
thetic limitation significantly hampered our ability to develop a general
and versatile trans-hydroboration protocol. Recognizing that N-vinyl-
B-Cl intermediate D (Scheme 3, top) contains a nucleophilic enamine
and an electrophilic boron atom, we envisioned that D could be poised
to undergo intramolecular electrophilic cyclization16 to furnish C3-
substituted monobenzofused 1,4-azaborine E after aromatization, thus
circumventing the limiting ring-closing-metathesis approach. Interme-
diate D should be accessible from commercially available 2-
bromoaniline, a variety of acyl chlorides, and (diisopropylamino)boron
dichloride.
boron substituent from o-diphenylphosphinophenyl to 2-
diphenylphosphinonaphth-1-yl group did not result in obvious trends
in terms of both reactivity and stereo-selectivity (Table 1, entries 2 vs.
5, and entry 3 vs. 6). The isolated yield of dienylboronate ester 5a
could be elevated to 86% when 1.5 equivalents of CatBH is used in-
stead of 1.0 equivalent (Table 1, entry 7).
1
2
3
4
5
6
7
8
Table 1. Ligand survey of trans-hydroboration of terminal 1,3-
enyne 4a catalyzed by L/Pd(0)
9
4 mol% L
2 mol% Pd2dba3
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H
H
HBCat
Ph
CH2Cl2, 0.25 M, RT, 30 min.
then pinacol (12.0 equiv)
Ph
B(pin)
4a
1.0 equiv
5a
Scheme 3. Retro-synthetic analysis and preparation of
Senphos Ligands L2-L6
trans-hydroboration
selectivitya
entry
yield (%)b
L
Me
Me
1) electrophilic
nucleophilic
cyclization
1
2
93:7
92:8
59
60
56
62
59
68
86
L1
L2
L3
L4
L5
L6
L4
N
NH2
N
Cl
O
BCl
X
R
Br
B
X
R
2) aromatization
3
96:4
R
electrophilic
i-Pr2NBCl2
E
D
4
>98:2
96:4
5
Me
N
Me
N
0.05 mol%
(PPh3)2(CO)IrCl
1) RCH2COCl, pyridine
CH2Cl2, 0 °C, 30 min
NH2
Br
6
94:6
R
R
7c
>98:2
O
PMHS, toluene
2) NaH, MeI
THF, 0 °C, 2 h
Br
Br
1a, R = Me, 82%
1b, R = Et, 92%
1c, R = iPr, 94%
2a, R = Me, 63%
2b, R = Et, 71%
2c, R = iPr, 86%
aThe diastereomeric ratio was determined by 1H NMR of crude material
before addition of pinacol; bYield of isolated product, based on 4a; c1.5
equiv of HBCat was applied. dba: dibenzylidineacetone.
1) n-BuLi,
2) i-Pr2NBCl2
THF, –78 °C
then
vaccum
distillation
Under optimized reaction conditions, various terminal E-1,3-enynes
4 were subjected to the trans-selective hydroboration, and the results
are summarized in Table 2. High yield and trans-selectivity were ob-
served consistently with an array of electronically and sterically differ-
ent substituents on the alkene. The stereochemistry of dienylboronate
5a was confirmed by single crystal X-ray diffraction analysis (Table 2).
Br
Me
N
Me
PPh2
Me
N
N
B
R
B
R
n-BuLi, THF, –78 °C
B
R
PPh2
PPh2
Cl
Table 2. Trans-hydroboration of terminal 1,3-enynes 4 cata-
lyzed by L4/Pd(0)
L2, R = Me, 58%
L3, R = Et, 67%
L4, R = iPr, 81%
3a, R = Me, 79%
3b, R = Et, 69%
3c, R = iPr, 94%
L5, R = Me, 75%
L6, R = Et, 68%
With a new synthetic strategy in hand, we began our synthesis of a
library of ligands with the acylation and methylation of 2-bromoaniline
to provide amides 1a-c. The critical enamine functionality was intro-
duced using a protocol developed by Nagashima.17 Treatment of 1 with
polymethylhydrosiloxane (PHMS) in the presence of 0.05 mol% of
Vasaka’s complex (PPh3)2(CO)IrCl as a catalyst furnished the corre-
sponding enamines 2a-c in 63-86% yield. Subsequent lithium-halogen
exchange followed by addition of i-Pr2NBCl2 and distillation of the
resulting reaction mixture under attenuated pressure afforded directly
the versatile B-Cl-substituted monobenzofused 1,4-azaborines 3a-c.18
The structure of 3a is further unambiguously confirmed by single crys-
tal X-ray diffraction analysis (see supporting information). Finally, the
substitution reaction of 3a-c with phosphine-containing organolithium
nucleophiles gave targeted SenPhos ligands L2-6.
4 mol% L4
2 mol% Pd2dba3
H
H
H
HBCat
R1
R1
CH2Cl2, 0.25 M, RT,
then pinacol (12.0 equiv)
1.5 equiv.
R2 B(pin)
R2
4
5
B(pin)
B(pin)
B(pin)
Me
Me
5a
85% (> 98 : 2)
5b
5c
X-ray structure of 5a
86% (> 98 : 2)
82% (98 : 2)
B(pin)
B(pin)
B(pin)
B(pin)
MeO
Me
5d
F
Cl
5e
5g
82% (98 : 2)
5f
80% (98 : 2)
76% (> 98 : 2)
88% (> 98 : 2)
B(pin)
B(pin)
S
B(pin)
B(pin)
We chose terminal E-1,3-enyne 4a as our initial substrate to probe
the effects of the ligand structure on the trans-hydroboration selectivi-
ty. In the presence of 4 mol% catalyst “L1 (= B)/Pd(0)”, reaction of 4a
with 1 equivalent of catecholborane (HBCat) in CH2Cl2 at room tem-
perature and subsequent transesterification with pinacol19 afforded the
corresponding trans-hydroboration product 5a with decent trans-
hydroboration stereo-selectivity (93 : 7) in 59% yield (Table 1, entry
1). No background reaction was observed in the absence of the catalyst
under otherwise identical reaction conditions. The C3-substituent in L
plays an important role in the optimization of stereo-selectivity. For
example, when L4, which bears the sterically more demanding i-Pr
group at the C3 position, is used as the ligand, the reaction gave superi-
or (> 98:2) trans-hydroboration selectivity compared to those with the
Br
5j
81% (> 98 : 2)
5h
5i
5k
81% (97 : 3)
76% (98 : 2)
80% (> 98 : 2)
Hexn
B(pin)
O
B(pin)
B(pin)
B(pin)
TBSO
5l
84% (97 : 3)
5m
5n
5o
86% (> 98 : 2)
82% (94 : 6)
87% (97 : 3)
Me Me
(H2C)9
TBSO
B(pin)
B(pin)
B(pin)
Me
5q
93% (95 : 5)
5p
91% (96 : 4)
5r
70% (97 : 3)
Yield of isolated product (average of 2 runs), based on 4.The diastereomeric ratio in parenthesis was
determined by 1H NMR of crude material before addition of pinacol.
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
The metal-catalyzed trans-hydroboration of internal 1,3-enynes is a
Our method is amendable to scale up. As can be seen from eq 2,
trans-hydroboration of 1,3-enyne 6l (1.138 g, 8.0 mmol) with a re-
duced catalyst loading (1 mol% Pd) furnished the desired product 7l in
89% yield (1.819 g) without erosion of stereo-selectivity.
1
2
3
4
5
6
7
8
significantly more demanding problem and has currently no precedent
in the literature. Internal 1,3-enynes are generally less reactive toward
hydroboration, and the control of both site- and stereoselectivity is
more challenging.20 Gratifyingly, when the concentration of the reac-
tion is increased from 0.25 M to 1.25 M,21 the reaction of internal E-
1,3-enyne 6a with CatBH (see eq 1) in the presence of 4 mol% L1/Pd
was complete within 90 minutes at room temperature, affording 7a in
89% yield with 90:10 trans-hydroboration selectivity after treatment
with pinacol. Other regioisomers were not observed. Further optimiza-
tion with regard to the ligand structure revealed that the C3-ethyl sub-
stituted L3 was the best performing ligand producing 7a in 92% yield
and 96:4 trans-hydroboration selectivity.22
1 mol% L3
0.5 mol% Pd2dba3
CH2Cl2, 30 min
Me
1.25 M
Me
Ph
(2)
HBCat
then pinacol (12.0 equiv)
Ph
B(pin)
1.5 equiv.
6l
7l
1.138 g
89% (> 98 : 2)
1.819 g
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dienylboronate esters such as 7l are versatile intermediates in organic
synthesis,23 and Scheme 4 illustrates that 7l is capable in engaging in
subsequent C-C bond forming transformations stereospecifically. For
example, 7l undergoes Pd catalyzed Suzuki-Miyaura24 coupling with
bromobenzene to furnish 1,3-diene 8 in 83% yield with complete re-
tention of the olefin stereochemistry (Scheme 4, eq 3). Furthermore,
Diels-Alder reaction of 7l with N-methylmaleimide afforded bicyclic 9
containing 4 stereogenic centers with high diastereoselectivity (en-
do/exo>98:2) in 67% yield (Scheme 4, eq 4).25 Finally, homologation
of 7l with deprotonated carbamate 10 followed by oxidation furnished
corresponding dienol 11 in 62% yield (Scheme 4, eq 5).26
4 mol% L
2 mol% Pd2dba3
H
Me
Me
HBCat
1.5 equiv.
(1)
CH2Cl2, 1.25 M. RT, 1.5 h
then pinacol (12.0 equiv)
B(pin)
6a
7a
The substrate scope for the trans-hydroboration of internal 1,3-
enynes is summarized in Table 3. In general, 1,4-disubstituted 1,3-
eynes 6 bearing an aryl group at R1 position gave superior trans-
hydroboration selectivity than alkyl groups (Table 3, entries 7h-7l vs.
7a-7g). Increasing the substituent size of the R3 substituent in 6 reduc-
es trans-hydroboration selectivity (Table 3, entries 7l-7p, in particular
7l vs. 7p). The bond connectivity of dienylboronate 7a and the hy-
droboration stereoselectivity were unambiguously confirmed by the
solid-state structure of 7a (Table 3).
Scheme 4. Functionalization of hydroboration product 7l
bromobenzene
2 mol% Pd2dba3
4 mol% S-Phos
Me
Me
Ph
(3)
Ph
Ph
THF/3 M NaOH
(v/v = 3: 1)
60 °C, 16 h
B(pin)
7l
8
Table 3. Trans-hydroboration of internal 1,3-enynes 6 cata-
lyzed by L3/Pd(0)
(> 98 : 2)
87% (> 98 : 2)
4 mol% L3
2 mol% Pd2dba3
Me
N-methylmaleimide
mesitylene
B(pin)
O
H
R3
Me
R3
(4)
HBCat
Ph
R1
N
Me
R1
CH2Cl2, 1.25 M, RT,
then pinacol (12.0 equiv)
170 °C, 3 days
B(pin)
R2 B(pin)
R2
O
6
7
Ph
7l
9
67%, endo/exo > 98: 2
OCb
Me
Me
B(pin)
(±)-
Hexn
10
Ph
Me
B(pin)
s-BuLi
ether, –78 °C
then RT, 2 hr
7a
7b
Me
Me
O
92% (96 : 4)
X-ray structure of 7a
80% (93: 7)
(5)
Ph
Ph
Me
Cb =
B(pin)
N(iPr)2
HO
Ph
then aq. H2O2
NaOH, THF
7l
nBu
Me
B(pin)
Et
B(pin)
11
Hexn
TBSO
Me
62% (> 98 : 2)
B(pin)
7c
93% (82 : 18)
7d
77% (81 : 19)
7e
84% (92 : 8)
We were able to obtain the single crystal X-ray structure of Senphos
L4 bound to Pd(0)dba. Scheme 5 shows that the κ2-P-η2-BC coordina-
tion mode to Pd(0) in complex 12 is preserved even with the sterically
demanding i-Pr group at the C(3) position.27,28 Complex 12 is a chemi-
cally and kinetically competent catalyst. Trans-hydroboration of sub-
strate 4a with the isolated Pd(0) complex 12 as the catalyst furnished
the desired product 5a in the same amount of yield and diastereoselec-
tive within 30 minutes as described in Table 1.
Me
B(pin)
Me
B(pin)
Me
TBSO(H2C)9
B(pin)
Me
7g
7f
89% (94 : 6)
7h
87% (> 98 : 2)
79% (97 : 3)
Me
Me
Me
B(pin)
B(pin)
B(pin)
Scheme 5. Isolated Pd(0) complex 12 is a competent catalyst for
trans-hydroboration
Cl
F
MeO
7j
7i
7k
90% (> 98: 2)
87% (> 98 : 2)
85% (> 98 : 2)
Me
N
nBu
B(pin)
Me
Et
B(pin)
i-Pr
B(pin)
B
Pd dba
7l
7m
96% (95 : 5)
7n
88% (93 : 7)
PPh2
88% (> 98 : 2)
nOctyl
B(pin)
OTBS
B(pin)
12
B(pin)
H
7o
7p
7q
4 mol% 12
H
90% (93 : 7)
86% (86 : 14)
86% (93 : 7)
H
HBCat
1.5 equiv
(6)
Ph
CH2Cl2, 0.25 M, RT, 30 min.
then pinacol (12.0 equiv)
Ph
B(pin)
Yield of isolated product (average of 2 runs), based on 6.The diastereomeric ratio in
parenthesis was determined by 1H NMR of crude material before addition of pinacol.
4a
5a
81% (> 98 : 2)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
1345. (c) Pan, J.; Kampf, J. W.; Ashe, A. J., III. J. Organomet. Chem. 2009, 694,
1036.
(5) For select other examples of coordination compounds associated with
single BN/CC replacement, see: (a) Bailey, J. A.; Haddow, M. F.; Pringle, P. G.
Chem. Commun. 2014, 50, 1432. (b) Bailey, J. A.; Ploeger, M.; Pringle, P. G.
Inorg. Chem. 2014, 53, 7763. (c) Ko, S. B.; Lu, J. S.; Wang S. Org. Lett. 2014, 16,
616.
(6) For leading references to 1,2-azaborolyl ligands as BN/CC isosteres of
the cyclopentadienyl ligand, see: (a) Schmid, G. Comments Inorg. Chem. 1985,
4, 17. (b) Liu, S.-Y.; Lo, M. M.-C.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41,
174.
(7) Xu, S.; Haeffner, F.; Li, B.; Zakharov, L. N.; Liu, S.-Y. Angew. Chem. Int.
Ed. 2014, 53, 6795.
(8) Matsumoto, Y.; Naito, M.; Hayashi T. Organometallics 1992, 11, 2732.
(9) For recent examples of non-transition-metal-mediated trans-
hydroboration, see: (a) Yuan, K.; Suzuki, N.; Mellerup, S. K.; Wang, X.; Yama-
guchi, S.; Wang, S. Org. Lett. 2016, 18, 720. (b) McGough, J. S.; Butler, S. M.;
Cade, I. A.; Ingleson, M. J. Chem. Sci. 2016, 7, 3384.
(10) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000, 122,
4990.
(11) Gunanathan, C.; Hoelscher, M.; Pan, F.; Leitner, W. J. Am. Chem. Soc.
2012, 134, 14349.
(12) Obligacion, J. V.; Neely, J. M.; Yazdani, A. N.; Pappas, I.; Chirik, P. J. J.
Am. Chem. Soc. 2015, 137, 5855.
In summary, we have developed a modular and concise synthesis of
1
2
3
4
5
6
7
8
monobenzofused 1,4-azaborine-based phosphine ligands. Their Pd(0)
complexes have been found to catalyze trans-hydroboration of both
terminal and internal E-1,3-enynes with high site- and stereo-selectivity
under mild conditions. The method is also amendable to gram-scale
synthesis without erosion of selectivity. Mechanistic studies including
the origin of trans-hydroboration selectivity and further application of
Senphos ligands in catalytic transformations are currently underway in
our laboratory.
9
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, spectroscopic data, and crystallographic data
(CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.”
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
AUTHOR INFORMATION
Corresponding Author
shihyuan.liu@bc.edu
(13) Jang, W. J.; Lee, W. L.; Moon, J. H.; Lee, J. Y.; Yun, J. Org. Lett. 2016,
18, 1390.
Present Addresses
§State Key Laboratory for Oxo Synthesis and Selective Oxidation, Su-
zhou Research Institute of LICP, Lanzhou Institute of Chemical Phys-
ics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China
(14) Sundararaju, B.; Fürstner, A. Angew. Chem. Int. Ed. 2013, 52, 14050.
(15) Two relatively expensive catalysts were involved that had to be used at
relatively high catalyst loadings: Grubbs second generation catalyst at 10 mol%
loading, and [(PPh3)3(CO)(Cl)RuH] at 2 mol% loading.
(16) For select recent examples, see: (a) Hatakeyama, T.; Hashimoto, S.;
Seki, S.; Nakamura, M. J. Am. Chem. Soc. 2011, 133, 18614. (b) Wang, X.-Y.;
Zhuang, F.-D.; Wang, R.-B.; Wang, X.-C.; Cao, X.-Y.; Wang, J.-Y.; Pei, J. J. Am.
Chem. Soc. 2014, 136, 3764.
(17) Motoyama, Y.; Aoki, M.; Takaoka, N.; Aoto, R.; Nagashima, H. Chem.
Commun. 2009, 1574.
(18) Compounds 3a-c are formed after the exchange of the B-Ni-Pr2 group
with the in situ generated HCl.
(19) In order to isolate dienylboronate, the catecholboronate was converted
to pinacolboronate prior to column chromatography using similar procedures in
reference 10. No erosion of stereochemistry was observed after transesterifica-
tion.
(20) Sasaki, Y.; Horita, Y.; Zhong, C.; Sawamura, M.; Ito, H. Angew. Chem.
Int. Ed. 2011, 50, 2778.
(21) At 0.25 M concentration, the reaction was sluggish.
(22) The use of an analogous carbonaceous ligand CC-L3 as the supporting
ligand in the hydroboration reaction of 6l led to incomplete conversion and
significant formation of cis- and 1,4-hydroboration byproducts, see Supporting
Information for details.
(23) Eberlin, L.; Tripoteau, F.; Carreaux, F.; Whiting, A.; Carboni, B.
Beilstein J. Org. Chem. 2014, 10, 237.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This research was supported by the National Institutes of Health
NIGMS (R01-GM094541) and Boston College start-up funds. We
thank Dr. Lev N. Zakharav for solving the X-ray structure for com-
pound 3a. S.-Y.L. thanks the Camille Dreyfus Teacher-Scholar Awards
Program for a Teacher-Scholar award and the Humboldt Foundation
for the Friedrich Wilhelm Bessel Research Award.
REFERENCES
(1) For an overview, see: (a) Liu, Z.; Marder, T. B. Angew. Chem. Int. Ed.
2008, 47, 242. (b) Bosdet, M. J. D.; Piers, W. E. Can. J. Chem. 2009, 87, 8. (c)
Campbell, P. G.; Marwitz, A. J. V.; Liu, S.-Y. Angew. Chem. Int. Ed. 2012, 51,
6074.
(2) (a) Wang, X.-Y.; Wang, J.-Y.; Pei, J. Chem. Eur. J. 2015, 21, 3528. (b)
Morgan, M. M.; Piers, W. E. Dalton Trans. 2016, 45, 5920.
(3) (a) Vlasceanu, A.; Jessing, M.; Kilburn, J. P. Bioorg. Med. Chem. 2015, 23,
4453. (b) Rombouts, F. J.; Tovar, F.; Austin, N.; Tresadern, G.; Trabanco, A. A.
J. Med. Chem. 2015, 58, 9287. (c) Sanchez Casado, M. R.; Ciordia Jimenez, M.;
Ariza Bueno, M.; Barriol, M.; Leenaerts, J. E.; Pagliuca, C.; Martinez Lamenca,
C.; De Lucas, A. I.; Garcia, A.; Trabanco, A. A.; Rombouts, F. J. R. Eur. J. Org.
Chem. 2015, 5221. (d) Davies, G. H.; Molander, G. A. J. Org. Chem. 2016, 81,
3771. (e) Amani, J.; Molander, G. A. Org. Lett. 2015, 17, 3624. (f) Molander, G.
A.; Wisniewski, S. R.; Amani, J. Org. Lett. 2014, 16, 5636. (g) Liu, L.; Marwitz,
A. J. V.; Matthews, B. W.; Liu, S.-Y. Angew. Chem. Int. Ed. 2009, 48, 6817. (h)
Abbey, E. R.; Zakharov, L. N.; Liu, S.-Y. J. Am. Chem. Soc. 2011, 133, 11508. (i)
Abbey, E. R.; Liu, S.-Y. Org. Biomol. Chem. 2013, 11, 2060. (j) Chrostowska, A.;
Xu, S.; Mazière, A.; Boknevitz, K.; Li, B.; Abbey, E. R.; Dargelos, A.; Graciaa, A.;
Liu, S.-Y. J. Am. Chem. Soc. 2014, 136, 11813. (k) Saif, M.; Widom, J. R.; Xu, S.;
Abbey, E. R.; Liu, S.-Y.; Marcus, A. H. J. Phys. Chem. B 2015, 119, 7985. (l)
Knack, D. H.; Marshall, J. L.; Harlow, G. P.; Dudzik, A.; Szaleniec, M.; Liu, S.-
Y.; Heider, J. Angew. Chem. Int. Ed. 2013, 52, 2599. (m) Rudebusch, G. E.;
Zakharov, L. N.; Liu, S.-Y. Angew. Chem. Int. Ed. 2013, 52, 9316.
(24) (a) Suzuki, A. Angew. Chem. Int. Ed. 2011, 50, 6722. (b) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457.
(25) Hilt, G.; Bolze, P. Synthesis 2005, 2005, 2091.
(26) Stymiest, J. L.; Bagutski, V.; French, R. M.; Aggarwal, V. K. Nature
2008, 456, 778.
(27) The κ2-P-η2-BC coordination mode to Pd(0) is also observed in solu-
tion, consistent with a significant upfield shift in the 11B NMR compared to
corresponding free ligand (32 ppm vs. 46 ppm).
(28) For leading references on the effects of Pd-arene interactions in cataly-
sis, see: (a) Arrechea, P. L.; Buchwald, S. L. J. Am. Chem. Soc. 2016, 138, 12486.
(b) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem.
Soc. 2005, 127, 4685. (c) Yin, J.; Rainka, M. P.; Zhang, X.-X.; Buchwald, S. L. J.
Am. Chem. Soc. 2002, 124, 1162.
(4) For leading examples of coordination compounds with direct involve-
ment of the azaborine ring atoms, see: (a) Ashe, A. J., III. Organometallics 2009,
28, 4236. (b) Pan, J.; Kampf, J. W.; Ashe,,A. J., III. Organometallics 2008, 27,
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment