Catalytic Use of Elemental Gallium for Carbon-Carbon Bond Formation

Article abstract of DOI:10.1021/jacs.6b06767

The first catalytic use of Ga(0) in organic synthesis has been developed by using a Ag(I) cocatalyst, crownether ligation, and ultrasonic activation. Ga(I)-catalyzed C-C bond formations between allyl or allenyl boronic esters and acetals, ketals, or aminals have proceeded in high yields with essentially complete regio- and chemoselectivity. NMR spectroscopic analyses have revealed novel transient Ga(I) catalytic species, formed in situ through partial oxidation of Ga(0) and B-Ga transmetalation, respectively. The possibility of asymmetric Ga(I) catalysis has been demonstrated.

Full text of DOI:10.1021/jacs.6b06767

Subscriber access provided by BOSTON UNIV
Communication
Catalytic Use of Elemental Gallium for Carbon–Carbon Bond Formation
Bo Qin, and Uwe Schneider
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b06767 • Publication Date (Web): 21 Sep 2016
Downloaded from http://pubs.acs.org on September 21, 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 11
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Catalytic Use of Elemental Gallium for
Carbon–Carbon Bond Formation
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
Bo Qin and Uwe Schneider*
The University of Edinburgh, EaStCHEM School of Chemistry, The King’s Buildings, David Brewster Road, EH9 3FJ Edꢀ
inburgh, UK
Supporting Information Placeholder
through partial oxidation of gallium(0) by a perfluoriꢀ
nated silver aluminate.9a Gallium(0) itself is not Lewis
acidic or basic, and has been used as a stoichiometric
reagent in Barbier chemistry (Scheme 1a–iii).13 Howevꢀ
er, gallium(0) displays several attractive features; it has a
relatively low first ionization potential,1,14 and is fairly
airꢀ and moistureꢀstable; furthermore, it can be easily
handled as it is liquid at ≈ 30 oC.1,14
ABSTRACT: The first catalytic use of Ga(0) in organic
synthesis has been developed by using a Ag(I) coꢀ
catalyst, crownether ligation, and ultrasonic activation.
Ga(I)ꢀcatalyzed C–C bond formations between allyl or
allenyl boronic esters and acetals, ketals, or aminals
have proceeded in high yields with essentially complete
regioꢀ and chemoselectivity. NMR spectroscopic analꢀ
yses have revealed novel transient Ga(I) catalytic speꢀ
cies, formed in situ through partial oxidation of Ga(0)
and B–Ga transmetalation, respectively. The possibility
of asymmetric Ga(I) catalysis has been demonstrated.
Scheme 1. Background and concept.
Advances in synthetic chemistry and/or catalyꢀ
sis rely on innovative concepts and the exploration of
unprecedented chemical species. In this context, galliꢀ
um (Ga) is an interesting main group metal; it is fairly
abundant and relatively inexpensive;1 it also displays
good functional group compatibility and low toxicity.1
In turn, species such as Ga clusters,2 Ga and GaP nanoꢀ
particles,3 GaAs crystals,4 or Ga phosphite frameworks5
have been recently exploited in various domains. In the
field of organic chemistry, gallium in its stable highꢀ
oxidation state +III has been thoroughly explored
(Scheme 1a–i). Indeed, due to its strong Lewis acidity,
gallium(III) has been widely used in catalysis.6
We envisioned that gallium(0) may be exploited
in catalysis if it can be converted in situ to gallium(I)
(Scheme 1b). Thereby, a potentially Lewis acidic and
basic catalyst may be generated, which may activate
both Lewis basic and acidic reagents for subsequent
bond formation. We report here the first catalytic use of
elemental gallium in organic synthesis through in situ
oxidation by silver(I) to generate a potentially amꢀ
biphilic gallium(I) species.
In contrast, the chemistry of gallium in the less
stable lowꢀoxidation state +I is largely underexplored
(Scheme 1a–ii). One reason may be the propensity to
undergo disproportionation to form gallium(III) and galꢀ
lium(0). Intriguingly, however, gallium(I) may display
both Lewis acidity and basicity because of the presence
of both vacant p orbitals and a lone pair.7,8 Depending
on the ligand/counteranion by which it is coordinated,
gallium(I) has been shown to act as stoichiometric Lewis
acid,9,10 Lewis base,11 or ambiphilic reagent.12 While
not commercially available, gallium(I) has been syntheꢀ
sized from gallium(III) or subꢀvalent gallium species
using strong reductants.11f Recently, Krossing and Slatꢀ
tery et al. have reported a seminal access to gallium(I)
In initial proofꢀofꢀconcept experiments for a
model reaction between acetal 1a and allyl boronic ester
2,15 we used gallium(0) (50 mol%) and silver triflate (10
mol%) in dioxane at 30–40 oC for 24 h (Table 1, entries
1 and 2). Although the virtual gallium(I) loading was
only 10 mol%, homoallyl ether 3a was obtained in 50–
55% yield; other solvents proved to be less efficient (see
SI). Significantly, the use of gallium(0) or silver triflate
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 11
alone resulted only in the recovery of starting materials the transformations using propargyl and allyl acetals
1
2
3
4
5
6
7
8
(entries 3 and 4). The reaction time was substantially
decreased by switching from conventional heating and
stirring to ultrasonication (8 h; entry 5); this result repreꢀ
sents a rare example for ultrasonic activation in catalyꢀ
sis.16 The Ga(0)/Ag ratio and the virtual Ga(I) loading
were decreased to 2:1 and 5 mol%, respectively, without
loss of activity (67% yield; entries 6 and 7). The use of
[18]crownꢀ6 {[18]cꢀ6} as a ligand to stabilize the anticiꢀ
pated in situ gallium(I) catalyst proved to be critical for
the full conversion of 1a to 3a (95–99% yield; entries 8
and 9). This reaction could be carried out on a gramꢀ
scale at low catalyst loading (0.1 mol%; see SI). The
prerequisite of a threeꢀcoordinate boron reagent, such as
2, was supported by unsuccessful reactions using fourꢀ
coordinate boron species 4 and 5 (Table 1). While toluꢀ
ene was shown to be a compatible solvent (90% yield;
entry 10), other silver salts or ligands displayed lower
reactivity (see SI). Control experiments in the absence
of Ga(0) or AgOTf failed to give 3a, thus confirming the
necessity of both catalyst components to generate in situ
a gallium(I) catalyst (entries 11 and 12). Likewise, a
control experiment with gallium(III) gave very poor reꢀ
activity (entry 13); similar results were obtained in conꢀ
trol reactions with other metal triflates or Ag(0) (see SI).
proved to be fully regioselective (v, w). Finally, chalꢀ
lenging ketals reacted smoothly to give quaternary carꢀ
bon centers (z, z’); in this context, a reactive ketone
group could be chemoselectively preserved (z’).
Scheme 2. Scope of acetals and ketals.a,b
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
Table 1. Initial results and reaction optimization.a
Next, we investigated catalytic intermediates
and the reaction mechanism (Scheme 3). In the absence
of 1 and 2, Ga(0) was reacted with AgOTf and [18]cꢀ6 in
dioxane under standard conditions resulting in a single
resonance at –566 ppm (71Ga NMR; Scheme 3a–i).
Based on literature,9a this chemical shift is consistent
with a novel Ga(I) species;19 we assume the Ga(I) center
being coordinated by dioxane in analogy to arene η6
complexes:20 [18]cꢀ6–Ga(I)
(dioxane)nOTf (6; n =
•
1,2,3). A solution of 6 was used to trigger C–C bond
formation between 1a and 2 (11B NMR: 33 ppm;
Scheme 3a–ii). Product 3a and byꢀproduct 7 were
formed quantitatively (11B NMR: 22 ppm), and the reꢀ
generation of gallium(I) catalyst 6 was confirmed (71Ga
NMR: –587 ppm).19
Next, 6 was reacted with acetal 1a to form oxoꢀ
carbenium ion species 8 –as detected by HRMS (ESI)21–
and the assumed [Ga(I)]–OMe species 919,22 (Scheme
3b–i). Subsequent addition of 2 resulted in the smooth
production of 3a (not shown). In contrast, 6 proved to
be unreactive toward boronic ester 2 as confirmed by
NMR analyses (Scheme 3b–ii). Thus, prior to the actiꢀ
vation of 2, Ga(I) catalyst 6 may activate 1a as a Lewis
acid (C–O bond cleavage, i.e., abstraction of –OMe). In
order to probe this scenario, 6 was reacted with boron–
ate complex 10 (11B NMR: 7 ppm), formed in situ from
2 and K–OMe (Scheme 3b–iii). A downꢀfield shift was
observed suggesting the formation of threeꢀcoordinate
boron species 7 (11B NMR: 22 ppm), which provided
unambiguous proof for C–B bond cleavage. Moreover,
Next, the scope of this catalytic C–C bond forꢀ
mation was examined (Scheme 2).17 Various aromatic,
heteroaromatic, aliphatic, and even cyclic acetals 1 were
converted to homoallyl ethers 3 in high yields under
mild conditions.18 Remarkably, sensitive or challenging
functionalities, such as ester, hydroxyl, and amino
groups, were tolerated by the catalyst system (c, h, i).
Likewise, in case of substrates bearing aryl chloride or
bromide units, catalyst decomposition via “classic”
Barbier reactivity13 was not observed (e, f). In addition,
ACS Paragon Plus Environment

Page 3 of 11
Journal of the American Chemical Society
we detected a single resonance at –624 ppm (71Ga
NMR), ascribed to novel allyl gallium(I) species 11 (B–
Ga transmetallation).19,23
We also carried out a deuterium labeling experꢀ
iment using 2–[d2] (Scheme 3c). Under standard condiꢀ
tions, regioisomers 3a–[d2] and 3’a–[d2] were obtained
in a 1:1 ratio. This result indicated that deuterium
scrambling must have occurred prior to C–C bond forꢀ
mation,24 which again supports B–Ga transmetalation.
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
Scheme 3. Mechanistic experiments.
Scheme 5. Additional scope.
Scheme 6. Asymmetric induction.
Based on these experiments25 we propose a catꢀ
alytic cycle (Scheme 4). Ga(I) catalyst 6, formed in situ
from Ga(0), may activate acetal or ketal 1 as a Lewis
acid to abstract an alkoxide (C–O bond cleavage). This
process would lead to two transient species, oxocarbeniꢀ
um ion 8 and [Ga(I)]–OR 9. This electronꢀrich Ga(I)
intermediate may convert boronic ester 2 to the active
nucleophile, either allyl gallium(I) species 11 or the corꢀ
responding boron–ate complex (C–B bond activation).
The active nucleophile would undergo C–C bond forꢀ
mation with 8 to give product 3 with regeneration of 6.
It is noted that the original concept of direct Ga(I) dual
catalysis is not borne out by this mechanism.
Finally, we investigated the possibility of an
asymmetric version (Scheme 6). The combined use of
Ga(0) and silver salt (R)ꢀ17 for the reaction between
racꢀ12 and 2 gave product (R)ꢀ13 in 60% yield with
40% ee.27 Control experiments confirmed that the presꢀ
ence of both elemental gallium and (R)ꢀ17 were critical
to both reactivity and selectivity (see SI). This transꢀ
formation represents the first example of asymmetric
induction for the catalytic use of Ga(0) and for Ga(I)
catalysis.
In summary, we have developed the first cataꢀ
lytic use of Ga(0), which relies on a mildly oxidizing
Ag(I) coꢀcatalyst. Crownether ligation and ultrasonic
activation have proved to be critical to the catalyst’s acꢀ
tivity. Ga(I)ꢀcatalyzed C–C bondꢀforming reactions beꢀ
tween allyl or allenyl boronic esters and acetals, ketals,
or aminals have proceeded in high yields with essentialꢀ
ly complete chemoꢀ and regioselectivity. NMR spectroꢀ
scopic analyses have revealed the in situ generation of
novel Ga(I) catalytic species, which distinguishes our
work from Ga(II) chemistry.19 Likewise, in contrast to
Ga(I), other metal triflates including Ga(III) have proved
to be catalytically inactive. We have also demonstrated
the possibility of asymmetric Ga(I) catalysis. This novel
This in situ gallium(I) catalysis was successfulꢀ
ly extended to the use of aminal racꢀ12 to give homoalꢀ
lyl amide racꢀ13 (Scheme 5a);18 ultrasonic activation
was not required. This concept proved to be also appliꢀ
cable to the use of allenyl boronic ester 14 (Scheme
5b).15 Aromatic or aliphatic acetals 1a or 1x were conꢀ
verted regioselectively to homopropargyl ethers 15a or
15x; AgF proved to be the best coꢀcatalyst.18 These
transformations highlight the synthetic utility of this
novel catalysis method.26
Scheme 4. Proposed catalytic cycle.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 11
(9) Examples for stoichiometric Ga(I) Lewis acidity: (a) Slattery, J.
scalable method is a rare example for ultrasonic activaꢀ
tion16 in catalysis, and may open up a new field in orꢀ
ganic synthesis.
M.; Higelin, A.; Bayer, T.; Krossing, I. Angew. Chem., Int. Ed. 2010,
49, 3228. (b) Higelin, A.; Haber, C.; Meier, S.; Krossing, I. Dalton
Trans. 2012, 41, 12011. (c) Higelin, A.; Keller, S.; Göhringer, C.;
Jones, C.; Krossing, I. Angew. Chem., Int. Ed. 2013, 52, 4941.
(10) While our work was in progress, Ga(I)ꢀinitiated isobutene
polymerization was reported: (a) Lichtenthaler, M. R.; Higelin, A.;
Kraft, A.; Hughes, S.; Steffani, A.; Plattner, D. A.; Slattery, J. M.;
Krossing, I. Organometallics 2013, 32, 6725. (b) Lichtenthaler, M.
R.; Maurer, S.; Mangan, R. J.; Stahl, F.; Mönkemeyer, F.; Hamann, J.;
Krossing, I. Chem. – Eur. J. 2015, 21, 157.
1
2
3
4
5
6
7
8
ASSOCIATED CONTENT
Supporting Information
Additional experiments, experimental details, and characꢀ
terization data (PDF).
9
(11) Examples for stoichiometric Ga(I) Lewis basicity: (a) Kuchta,
M. C.; Bonanno, J. B.; Parkin, G. J. Am. Chem. Soc. 1996, 118,
10914. (b) Schmidt, E. S.; Jockisch, A.; Schmidbaur, H. J. Am. Chem.
Soc. 1999, 121, 9758. (c) Hardman, N. J.; Power, P. P.; Gorden, J. D.;
Macdonald, C. L. B.; Cowley, A. H. Chem. Commun. 2001, 1866. (d)
Baker, R. J.; Jones, C.; Platts, J. A. J. Am. Chem. Soc. 2003, 125,
10534. (e) Jones, C.; Junk, P. C.; Platts, J. A.; Stasch, A. J. Am.
Chem. Soc. 2006, 128, 2206. (f) Dange, D.; Choong, S. L.; Schenk,
C.; Stasch, A.; Jones, C. Dalton Trans. 2012, 41, 9304.
(12) Stoichiometric Ga(I) ambiphilicity: Prabusankar, G.; Gemel,
C.; Parameswaran, P.; Flener, C.; Frenking, G.; Fischer, R. A. Angew.
Chem., Int. Ed. 2009, 49, 5526.
(13) (a) Araki, S.; Ito, H.; Butsugan, Y. Appl. Organomet. Chem.
1988, 2, 475. (b) Lee. P. H. Bull. Korean Chem. Soc. 2007, 28, 17. (c)
Goswami, D.; Chattopadhyay, A.; Sharma, A.; Chattopadhyay, S. J.
Org. Chem. 2012, 77, 11064.
(14) http://chemglobe.org/ptoe/_/31.php
(15) Precedent for this reaction: Schneider, U.; Dao, H. T.; Kobaꢀ
yashi, S. Org. Lett. 2010, 12, 2488.
AUTHOR INFORMATION
Corresponding Author
*uwe.schneider@ed.ac.uk
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
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The School of Chemistry, the Royal Society, the EU
(PCIG10–GA–2011–304218), Eli Lilly, and AstraZeneca
are greatly acknowledged for financial support. We thank
Dr. John Slattery, The University of York, for helpful disꢀ
cussion.
(16) Ultrasonic activation in catalysis: AhmedꢀOhmer, B.; Barrow,
D.; Wirth, T. Chem. Engin. J. 2008, 135S, S280.
(17) Seminal report on the use of allyl silanes and acetals: (a) Hoꢀ
somi, A.; Endo, M.; Sakurai, H. Chem. Lett. 1976, 5, 941; (b) see also
references cited in ref. 15.
REFERENCES
(1) Downs, A. J.; Himmel, H.ꢀJ., New Light on the Chemistry of
the Group 13 Metals. In The Group 13 Metals Aluminium, Gallium,
Indium and Thallium: Chemical Patterns and Peculiarities; Aldridge,
S.; Downs, A. J., Eds.; John Wiley & Sons, Ltd.: Chichester, 2011 (1st
edition); p 1.
(18) In the absence of Ga(0), reactions did not occur.
(19) Evidence for Ga(II) or Ga(III) was not found under standard
conditions; key reference for Ga(II): Protchenko, A. V.; Dange, D.;
Harmer, J. R.; Tang, C. Y.; Schwarz, A. D.; Kelly, M. J.; Phillips, N.;
Tirfoin, R.; Birjkumar, K. H.; Jones, C.; Kaltsoyannis, N.; Mountford,
P.; Aldridge, S. Nat. Chem. 2014, 6, 315.
(20) (a) Schmidbaur, H. Angew. Chem., Int. Ed. 1985, 24, 893. (b)
Dohmeier, C.; Loos, D.; Schnöckel, H. Angew. Chem., Int. Ed. 1996,
35, 129. (c) see ref. 9a.
(21) In the absence of Ga(0), 8 was not detected when AgOTf,
[18]cꢀ6, and 1a were reacted under identical conditions.
(22) Unlike in 6, no signal was observed in the 71Ga NMR specꢀ
trum of 9; for similar cases, see refs. 9b–c.
(23) C–C bond formation between 10 and 1a did not proceed in the
absence of Ga(I) catalyst 6.
(24) 2ꢀ[d2], 3a–[d2], and 3’a–[d2] proved to be stable; deuterium
scrambling via 1,3ꢀboratropic rearrangement {2ꢀ[d2]} or product inꢀ
terconversion {3a–[d2], 3’a–[d2]} were not detected.
(25) Control experiments using 6 in the presence of Hg(0) or after
hot filtration strongly suggest homogeneous Ga(I) catalysis.
(26) The use of 1a, under Ga(I) catalysis, with a proꢀnucleophile
such as Ph–B(pin), octyl–B(pin), or a ketoneꢀderived silyl enol ether
failed to give C–C bond formation.
(2) Breaux, G. A.; Hillman, D. A.; Neal, C. M.; Benirschke, R. C.;
Jarrold, M. F. J. Am. Chem. Soc. 2004, 126, 8628.
(3) (a) Sun, J.; Liu, C.; Yang, P. J. Am. Chem. Soc. 2011, 133,
19306. (b) Yarema, M.; Wörle, M.; Rossell, M. D.; Erni, R.; Caputo,
R.; Protesescu, L.; Kravchyk, K. V.; Dirin, D. N.; Lienau, K.; von
Rohr, F.; Schilling, A.; Nachtegaal, M.; Kovalenko, M. V. J. Am.
Chem. Soc. 2014, 136, 12422.
(4) Fahrenkrug, E.; Gu, J.; Maldonaldo, S. J. Am. Chem. Soc. 2013,
135, 330.
(5) Sie, M.ꢀJ.; Lin, C.ꢀH.; Wang, S.ꢀL. J. Am. Chem. Soc. 2016,
138, 6719.
(6) Examples for Ga(III) catalysis: (a) Iida, T.; Yamamoto, N.; Saꢀ
sai, H.; Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 4783. (b) Simꢀ
mons, E. M.; Sarpong, R. Org. Lett. 2006, 8, 2883. (c) Prakash, G. K.
S.; Mathew, T.; Panja, C.; Alconcel, S.; Vaghoo, H.; Do, C.; Olah, G.
A. Proc. Nat. Acad. Sci. 2007, 104, 3703. (d) Mihara, H.; Xu, Y.;
Shepherd, N. E.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc.
2009, 131, 8384. (e) Bour, C.; Gandon, V. Coord. Chem. Rev. 2014,
279, 43. (f) Li, L.; Fan, S.; Mu, X.; Mi, Z.; Li, C.ꢀJ. J. Am. Chem. Soc.
2014, 136, 7793. (g) Abdalla, J. A. B.; Riddlestone, I. M.; Tirfoin, R.;
Aldridge, S. Angew. Chem., Int. Ed. 2015, 54, 5098.
(7) Aldridge, S. Angew. Chem., Int. Ed. 2006, 45, 8097.
(8) Ga(I) is not to be mistaken with “GaI”, which is a mixture of
subꢀvalent gallium iodides: (a) Baker, R. J.; Jones, C. Dalton Trans.
2005, 1341. (b) Malbrecht, B. J.; Dube, J. W.; Willans, M. J.;
Ragogna, P. J. Inorg. Chem. 2014, 53, 9644.
(27) Precedent for this reaction: Huang, Y.ꢀY.; Chakrabarti, A.;
Morita, N.; Schneider, U.; Kobayashi, S. Angew. Chem., Int. Ed.
2011, 50, 11121.
ACS Paragon Plus Environment

Page 5 of 11
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

Journal of the American Chemical Society
Page 6 of 11
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
(a) Chemistry of gallium in its oxidation states +III, +I, and 0:
ii
i
iii
L
L
Ga(+III):
L
Ga
Ga(+I):
L
Ga
Ga
Ga(0):
Lewis acid only
catalytic use
Lewis acid or base
stoichiometric use
no Lewis acidity or basicity
stoichiometric use
(b) Our concept for catalytic use of Ga(0) – in situ ambiphilic Ga(I) catalysis:
+I
Ga(+I):
potentially a Lewis
acid and base
catalyst in synthetic
organic chemistry ?
in situ
L
Ga
Ga(0)
(catalytic)
+
– Ag(0)
Ag(I)
Me
X
X
O
Me
Me
B
R
OR'
R
– R'O–B(pin)
O
Me
Lewis basic reagent
Lewis acidic reagent
X = OR', NH–PG
ACS Paragon Plus Environment

Page 7 of 11
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
OMe
OMe
Ga(0), AgOTf, [18]c-6
+
B(pin)
Ph
OMe
1a
Ph
conditions
2
(1.1 equiv)
3a
9
Ga(0)
[mol%]
AgOTf
[mol%]
[18]c-6
[mol%]
entry
yield [%]a
conditions
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
1b
2
3
4
5
6
7
8
50
50
50
–
10
10
–
dioxane, 30 oC, 24 h
50
55
NR
NR
57
67
67
95
99
90
NR
NR
3
–
–
dioxane, 40 oC, 24 h
dioxane, 40 oC, 24 h
–
dioxane, 40 oC, 24 h
–
10
10
10
5
dioxane, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
toluene, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
dioxane, ))), 40–45 oC, 8 h
–
50
20
10
10
10
10
10
–
–
–
5
5
9c,d
10
5
10
10
10
10
10
5
–
11
12
5
13e
Ga(OTf)3 (5)
a Yields are 1H NMR yields determined with an aliquot
vs. Bn2O as internal standard. b The use of other
solvents gave 3a in 12–36% yields (see SI). c The use
of other silver salts and ligands gave 3a in 0–73% yields
(see SI). d When four-coordinate allyl boron species 4
and 5 were used (instead of 2), no reaction occurred.
MeN
O
–BF3 K+
B O
O
O
4
5
e Control experiments with other metal triflates or Ag(0) gave 3a in 0–4% yields (see SI).
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 11
1
2
3
OMe
4
5
OMe
OMe
Me
6
7
8
X
3m: 1–naphthyl; 91% yield
3n: 2–naphthyl; 91% yield
3k: 3–Me; 91% yield
3l: 2–Me; 90% yield
9
3a: X = H; 91% yield
3b: X = CF3; 92% yield
3c: X = CO2Me; 92% yield
3d: X = F; 89% yield
3e: X = Cl; 92% yield
3f: X = Br; 92% yield
3g: X = Me; 94% yield
3h: X = CH2OH; 57% yield
3i: X = NMe2; 54% yield
3j: X = OMe; 93% yield
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
OR
O
3q: 80% yield
3o: R = Et; 87% yield
3p: R = Bn; 88% yield
OMe
OMe
OEt
O
Ph
X
Ph
3r: 90% yield
3s: X = 3–NBoc; 84% yield
3t: X = 2–O; 90% yield
3u: X = 2–S; 80% yield
3v: 85% yield
3w: 72% yield
Ph OMe
OMe
OMe
Ph
OMe
Ph
O
tBu
Ph
3y: 80% yield
3z: 91% yield
3z': 82% yield
3x: 84% yield
a Reaction conditions: 1, Ga(0) (10 mol%), AgX (X = OTf or F; 5 mol%), [18]c-6 (10 mol%), 2
(1.1–1.5 equiv), dioxane or toluene, ))), 40–50 oC, 8–78 h. b All yields are isolated yields after
preparative thin-layer chromatography (PTLC) on silica gel.
ACS Paragon Plus Environment

Page 9 of 11
Journal of the American Chemical Society
1
2
3
4
5
6
(a) Generation, characterization, and regeneration of Ga(I) (71Ga & 11B NMR):
1a
+
2
[11B: 33 ppm]
ii
i
+
+
Ga(0)
AgOTf
(0.5 equiv)
[18]c-6
40 oC, 4 h
7
6 (100 mol%)
8
9
– Ag(0) dioxane, ))), 40–45 oC, 36 h
3a
>99% yield
MeO–B(pin) (7)
[11B: 22 ppm]
+
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
[18]c-6–Ga(I)•(dioxane)nOTf (6)
[71Ga: –566 ppm]
regenerated 6 [
71Ga: –587 ppm]
(b) Reactivity of Ga(I) with substrates and boron–ate complex (71Ga & 11B NMR):
+OMe –OTf
i
1a
[Ga(I)]–OMe (9)
71Ga: no signal]
+
40 oC, 2 h
Ph
H
[
8
[HRMS (ESI)]
2 [
11B: 33 ppm]
ii
NR [71Ga & 11B: no change]
6
40 oC, 24 h
(100 mol%)
[71Ga: –566 ppm]
OMe
–B(pin) K+
10 [11B: 7 ppm]
40 oC, 2 h
– KOTf
[Ga(I)]
71Ga: –624 ppm]
7
[Ga(I)]
+
[11B: 22 ppm]
iii
11
[
(c) Deuterium labelling experiment (1H & 2H NMR):
Ga(0) (10 mol%), AgOTf (5 mol%)
[18]c-6 (10 mol%)
OMe
OMe
OMe
+
D
Ph
OMe
1a
Ph
Ph
dioxane, ))), 40–45 oC, 8 h
D D
D
B(pin)
2–[d2]
(1.5 equiv)
D D
3a–[d2]
3'a–[d2]
80% yield (1:1)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 11
1
2
3
4
5
6
7
8
[Ga(I)] = [18]c-6–Ga(I)•(solvent)nX, with X = OTf or F
C–O bond cleavage
O
R
OR''
R'
[Ga(I)]–OR'' (9)
1
9
B(pin)
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
AgX
[18]c-6
2
X
O
Ga(0)
[Ga(I)] (6)
8
C–B bond
activation
)))
R
R'
– Ag(0)
[Ga(I)]
11
[Ga(I)]
O
C–C bond formation
&
catalyst recycle
or
R
R'
allyl boron–ate
complex
3
Bz
Ga(0) (10 mol%), AgOTf (5 mol%)
[18]c-6 (10 mol%)
Bz
(a)
HN
Ph
HN
Ph
dioxane, 50 oC, 24 h
B(pin)
OMe
rac-12
rac-13
83% yield
2
(1.2 equiv)
(b)
Ga(0) (10 mol%), AgF (5 mol%)
[18]c-6 (10 mol%)
OMe
OMe
OMe
+
•
R
OMe
R
R
dioxane, ))), 40–45 oC, 52–72 h
15
16
B(pin)
•
1a: R = Ph
R = Ph: 91% yield; 15a:16a = 49:1
R = (CH2)2Ph: 82% yield; 15x:16x = >30:1
14
(1.2 equiv)
1x: R = (CH2)2Ph
ACS Paragon Plus Environment

Page 11 of 11
Journal of the American Chemical Society
1
2
3
4
5
6
Ga(0) (15 mol%)
(R)-17 (7.5 mol%)
Bz
Bz
HN
Ph
HN
Ph
B(pin)
+
toluene, 40 oC, 5 d
OMe
7
8
rac–12
2
(1.5 equiv)
(R)-13
60% yield, 40% ee
Ar
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
O
O
O
P
OAg
Ar
(R)-17 [Ar = 3,5–(tBu)2–C6H3]
ACS Paragon Plus Environment