Catalytic Boration of Alkyl Halides with Borane without Hydrodehalogenation Enabled by Titanium Catalyst

Article abstract of DOI:10.1002/anie.202100569

An unprecedented and general titanium-catalyzed boration of alkyl (pseudo)halides (alkyl-X, X=I, Br, Cl, OMs) with borane (HBpin, HBcat) is reported. The use of titanium catalyst can successfully suppress the undesired hydrodehalogenation products that prevail using other transition-metal catalysts. A series of synthetically useful alkyl boronate esters are readily obtained from various (primary, secondary, and tertiary) alkyl electrophiles, including unactivated alkyl chlorides, with tolerance of other reducing functional groups such as ester, alkene, and carbamate. Preliminary studies on the mechanism revealed a possible radical reaction pathway. Further extension of our strategy to aryl bromides is also demonstrated.

Full text of DOI:10.1002/anie.202100569

Angewandte
Communications
Chemie
How to cite:
International Edition: doi.org/10.1002/anie.202100569
German Edition: doi.org/10.1002/ange.202100569
Boration
Catalytic Boration of Alkyl Halides with Borane without
Hydrodehalogenation Enabled by Titanium Catalyst
Xianjin Wang, Penglei Cui, Chungu Xia,* and Lipeng Wu*
Abstract: An unprecedented and general titanium-catalyzed
boration of alkyl (pseudo)halides (alkyl-X, X = I, Br, Cl,
OMs) with borane (HBpin, HBcat) is reported. The use of
titanium catalyst can successfully suppress the undesired
hydrodehalogenation products that prevail using other tran-
sition-metal catalysts. A series of synthetically useful alkyl
boronate esters are readily obtained from various (primary,
secondary, and tertiary) alkyl electrophiles, including unacti-
vated alkyl chlorides, with tolerance of other reducing func-
tional groups such as ester, alkene, and carbamate. Preliminary
studies on the mechanism revealed a possible radical reaction
pathway. Further extension of our strategy to aryl bromides is
also demonstrated.
A
lkyl boronate esters are synthetically valuable compounds
in organic chemistry as cross-coupling partners with various
electrophiles.[1] Their applications in medicinal chemistry
have also been demonstrated by bortezomib, which is an
approved drug for treating relapsed multiple myeloma and
mantle cell lymphoma.[2] Traditionally, they were produced
via the transmetallation of reactive organometallic reagents
(alkyl-Li or alkyl-MgX) with trialkoxyboranes (Sche-
me 1a).[3] Advanced synthetic approaches include olefin
Scheme 1. Methods for the synthesis of alkyl boronate esters: a) trans-
metallation of organometallic reagents with trialkoxyboranes; b) cata-
lytic boration of alkyl halides with diborons; c) catalytic boration of
octyl bromide with HBpin: comparison of known transition-metal
catalysts and our current system.
hydroboration,[4] alkane C H bond boration[5] and b-boration
À
of unsaturated carbonyl compounds.[6] It is noted that in
recent years, efforts have been devoted to the catalytic
boration of alkyl halides as an alternative approach for the
synthesis of alkyl boronate esters with the advantages of a)
using abundant or easily accessed alkyl halides as starting
material and b) avoiding the regioselectivity issues in the
(hydro)boration of alkenes and alkanes (Scheme 1b). In this
respect, transition-metal catalysts such as Cu,[7] Ni,[8] Pd,[9]
Rh,[10] Zn,[11] Fe,[12] Mn,[13] Ag,[14] and a stoichiometric amount
tBuOLi-mediated,[15] and photo-induced boration of alkyl
halides[16] have been developed that greatly improved the
access to alkyl boronate esters. However, the known proce-
dures all make use of diboron (B2pin2 or B2Cat2) as the
boration reagent. To our knowledge, the use of another
commonly used boration reagent borane (HBpin or HBcat)
for the direct boration of alkyl halides is not known.[17] The
main reason might be the dominated hydrodehalogenation
reaction when react alkyl halides with borane using tran-
sition-metal catalysts (Scheme 1c).[18] Indeed, either there
were no reactions or > 53% of the corresponding hydro-
dehalogenated saturated hydrocarbon were obtained when
applying the known procedures/catalysts for the reaction of
octyl bromide with HBpin (Scheme 1c, see Scheme S1 for
details). Only the iron catalyst gave 16% of the expected alkyl
boronate ester; however, this was accompanied by 80% of the
hydrodehalogenation product. Those results clearly demon-
strated the challenges of using borane for alkyl halide
boration reactions.
[*] X. Wang, Prof. C. Xia, Dr. L. Wu
State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Suzhou Research Institute of LICP, Lanzhou Institute of Chemical
Physics (LICP), Chinese Academy of Sciences
Lanzhou, 730000 (P. R. China)
E-mail: cgxia@licp.cas.cn
lipengwu@licp.cas.cn
Dr. P. Cui
College of Science, Hebei Agricultural University
Baoding 071001 (P. R. China)
To achieve this goal, we thought that an alternative early-
transition-metal catalyst might work, because early-transi-
tion-metals often have different structures and orthogonal
reactivities compared with late-ones.[19] In addition, several of
them are earth-abundant, especially titanium. We then
became interested in exploring the possibility of using
titanium catalysts to realize the boration of alkyl halides
X. Wang
University of Chinese Academy of Sciences
Beijing, 100049 (P. R. China)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202100569.
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
ꢀ 2021 Wiley-VCH GmbH
1
These are not the final page numbers!

Angewandte
Communications
Chemie
with borane (HBpin or HBcat). Herein, by applying titano-
cene complex as a catalyst, we could successfully suppress the
hydrodehalogenation product to only 3%; remarkably, the
boration product was obtained in 91% yield (Scheme 1c).
To start the investigation, a toluene solution of octyl
bromide (1a, 0.2 mmol) with HBpin (2a, 0.4 mmol, 2 equiv)
was reacted at 1008C with Cp2TiCl2 (10 mol%) as the
catalyst, however, only 12% of the hydrodehalogenation
product 4a was obtained (Table 1, entry 1). We then found
strategy. First, the reaction of primary alkyl bromides was
performed, and we were pleased to find that our methodology
worked well for a series of simple and substituted alkyl
bromides (Scheme 2). Unactivated linear alkyl bromides with
different carbon-chain lengths (6–9) were readily borated and
gave the resulting saturated alkyl boronate ester in yields of
up to 89% (3a–3d). Cyclohexyl-, methyl- and phenyl-
substituted alkyl bromides also reacted without problems
(3e–3i). Significantly, other reducible functional groups such
=
as esters and C C also survived (3j–3l). Different substitu-
Table 1: Determination of optimal reaction conditions.[a]
ents including heteroatoms on the 2-position of ethyl
bromides such as phenyl, 4-CF3-phenyl, 3-thiophenyl, dihy-
drobenzofuran and ketals were well tolerated, and 60–89%
yields of the corresponding alkyl boronate esters were
obtained (3m–3r). Alkyl bromides with various ether func-
À
tional groups reacted without interfering with the C O bonds
Entry
X
Base
Solvent
Y
[8C]
Yield [%][b]
(76–90% yields, 3s–3w). A thiol ether functional group was
also tolerated (3x). In addition, substituents such as -Bpin,
-Br and the possible hydroborated ester functional groups on
the attached phenyl ring were untouched (3y–3aa). Further-
more, N-atom-containing heterocycles such as indole, carba-
zole and phthalamide remained intact in our system with up
to 86% yields of 3ab–3ad obtained.
(mol%)
3a
4a
1
2
3
4
5
6
7
8
9
10
11
12
13[c]
10
10
10
–
10
10
10
10
10
5
–
toluene
toluene
toluene
toluene
THF
hexane
dioxane
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
100
100
100
100
100
100
100
100
80
80
60
80
60
–
6
12
7
MeOK
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
MeOLi
65
–
21
28
72
18
2
3
1
1
3
27
46
81
91
85
89
72
65
81
Then, we found that directly applying our optimized
reaction condition to 2-bromooctane resulted in 32% of the
hydrodehalogenation product but only trace amount of the
corresponding alkyl boronate ester was obtained with 1- and
2-octenes as the major undesired products. However, this
problem could be solved using HBcat as the boration reagent
and K2CO3 as the base in which case 58% of the correspond-
ing alkyl boronate ester (3ao) could be obtained. Other
boranes such as 9-BBN and HBdan gave much worse results
(Scheme S2).
Then, the substrate scope with respect to secondary alkyl
bromides was studied (Scheme 2). In general, moderate to
excellent yields were obtained. Cyclic, bicyclic, tricyclic and
acyclic secondary bromides with different substituents and
hetero-atoms underwent boration reactions smoothly, with up
to 95% yields of the corresponding boronate ester obtained
(3ae–3ao).
Secondary bromides with carbamate functional group
reacted without problems with the carbamate functional
group kept intact (3ap, 3aq). Apart from primary and
secondary alkyl bromides, tertiary alkyl bromides could also
be boronated. For example, the reaction of 1-bromoadaman-
tane proceeded smoothly to produce the boronated product
3ar in 63% yield. Tertiary alkyl bromides derived from cedrol
gave 66% of boronate ester 3as. Furthermore, the boration of
epiandrosterone and cholesterol-derived bromides gave the
corresponding boronate esters 3at and 3au in 56% and 68%
yields, which allowed for further modifications.
With the successful boration of alkyl bromides, we then
considered if our system could also boronate other alkyl
electrophiles, especially the more inert and challenging
unactivated alkyl chlorides. Notice that very few systems are
known to be able to boronate alkyl chlorides with acceptable
yields using diborons.[7a,d,10,13] To our delight, with our system,
various alkyl chlorides including unactivated acyclic, cyclic,
and heteroatom-containing alkyl chlorides were readily
10
1
5
3
5
[a] Reaction conditions: 0.2 mmol 1a, 0.4 mmol 2a, Cp2TiCl2 (1–
10 mol%), 0.2 mmol of bases, 1 mL of solvents in 38 mL pressure tube
at temperature shown in the table for 8–12 h; [b] yields were determined
by GC/MS with dodecane as internal standard; [c] 24 h. MTBE=methyl
tert-butyl ether.
that the addition of MeOK had some beneficial influence, in
which case 6% of the boration product 3a and 7% of the
hydrodehalogenation product 4a were obtained (Table 1,
entry 2). Encouraged by this result, further study on the base
effect was conducted (see Table S1 for details), and MeOLi
was found to be the optimal base, in which case we could
obtain 65% of 3a and 21% of 4a (Table 1, entry 3). Here, it is
noted that with only MeOLi, 4a was produced in 28% yield
(Table 1, entry 4). Other titanium-based catalysts gave infe-
rior results (see Table S2 for details). The solvent effect was
then studied (Table 1, entries 5–8, Table S3). Interestingly, the
solvent did have an obvious effect on the yields and
selectivities of 3a and 4a, and MTBE was established as the
best solvent, which gave 3a in 91% yield (Table 1, entry 8). In
addition, we could further reduce the reaction temperature to
808C and catalyst loading to 5 mol% without significantly
reducing the yields of 3a (85% and 89%, respectively)
(Table 1, entries 9, 10, Table S4–6). Notice that, even at 608C
or with 1 mol% of catalyst, we could still obtain relatively
good results (Table 1, entries 11, 12, Table S4–6). Finally, with
a longer reaction time, 81% of 3a could be obtained at 608C
(Table 1, entry 13).
Under the optimized reaction conditions (Table 1,
entry 13), we then studied the substratesꢀ generality of our
2
www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
These are not the final page numbers!

Angewandte
Communications
Chemie
Scheme 2. Reaction conditions: 1 (0.2 mmol), HBpin (2.0 equiv, 0.4 mmol), Cp2TiCl2 (5 mol%), MeOLi (1.0 equiv, 0.2 mmol), MTBE (1 mL),
608C, 24 h, yields of isolated products are given. [a] Reaction performed at 1008C; [b] 1 (0.2 mmol), HBcat (3.0 equiv, 0.6 mmol), Cp2TiCl2
(5 mol%), K2CO3 (1.0 equiv, 0.2 mmol), 808C, MTBE (1 mL), 24 h.
boronated with yields of up to 88% (Table 2, entries 1–8). In
addition, other electrophiles such as alkyl iodide and alkyl
mesylate also worked in our system (Table 2, entries 9–10).
Monitoring the standard reaction of 1a at 608C, we found
that the hydrodehalogenation product 4a only start to appear
after 4 h when the production of boronated product 3a
became slower. At no time did we observe the presence of
elimination product alkenes (Figure S1). Then, several con-
trol experiments were conducted to understand the detailed
reaction process. First, the reaction of a secondary bromide
(2-bromopropyl)benzene 4aa under our standard reaction
conditions regioselectively gave b-branched boronate ester
3i’ in 83% yield (Scheme 3a). On the other hand, the use of
possible elimination product from 4aa, allylbenzene 4b or b-
methylstyrene 4c, gave either mainly linear boronate ester 3i
or a-branched boronate ester 3i’’ as the major product
(Scheme 3b, c), the reaction of which ruled out the reaction
pathway of in situ formed alkene from alkyl halides and
subsequent hydroboration. The reaction of 1-bromo-2,2-
dimethylpropane 4d, which has no b-H, gave the expected
boronate ester 5d, which also ruled out alkene intermediate
mechanism (Scheme 3d).
Given the known formation of a radical species from alkyl
halides via single-electron transfer,[7d,e,8,16a,20] we then consid-
ered if a radical species is involved in our system. Then,
1 equiv of different radical scavengers, tempo and galvinoxyl,
were separately added to our system, interestingly, total
suppression of the boration reaction was observed (Sche-
me 3e). Alternatively, the addition of increasing amount of 9,
10-dihydroanthracenes or di-tert-butyl peroxide to the stan-
dard reaction, decreasing yields of 3a were observed
(Scheme S3). Using cyclopropylmethyl bromide 4e as the
electrophile with 3 equiv of HBpin, diborated product 5e was
obtained in 68% isolated yield, which was most likely
produced via a radical ring-opening intermediate, 3-butenyl-
boronate, supporting a radical mechanism (Scheme 3 f).
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
3
These are not the final page numbers!

Angewandte
Communications
Chemie
Table 2: Titanium-catalyzed direct boration of other alkyl electrophiles
radical species (Scheme 3g). From those results, it is reason-
able to propose a radical reaction pathway for our current
system. It has been well-demonstrated that Cp2TiIIICl gen-
erated in situ from Cp2TiCl2 is an excellent one-electron
transfer reagent,[21] and single-electron reduction of alkyl
halides to radical species is known.[7d,e,8,16a,20] Thus, it is likely
that Cp2TiIIICl species is generated in our system and initiate
a radical reaction pathway.[22] Currently, it is proposed that
Cp2Ti(H)Cl was first formed from Cp2TiCl2/MeOLi/HBpin
system, and then intermolecular reductive elimination of
molecular hydrogen provided Cp2TiIIICl species as was
previously reported.[23] Further studies and proofs of the
above mechanism are underway.
with borane.[a]
Then to further extend the application generality of our
strategy, the direct boration of aryl bromide with HBpin was
conducted.[16a,24] We were pleased to find that our method-
ology worked well for various aryl bromides with electroni-
cally and sterically varied substituents (Scheme 4). Electron-
donating groups such as -Me, -Et, -OMe at different positions
on the phenyl ring reacted properly in our system (up to 79%
isolated yields, 6a–6 f).
[a] Reaction conditions: alkyl electrophiles (0.2 mmol), HBpin (2.0 equiv,
0.4 mmol), Cp2TiCl2 (5 mol%), MeOLi (1.0 equiv, 0.2 mmol), MTBE
(1 mL), 1008C, 24 h; [b] yields of isolated products are given; [c] reaction
performed at 508C, GC yield; [d] reaction performed at 1008C, GC yield.
Scheme 4. Reaction conditions: 5 (0.2 mmol), HBpin (2.0 equiv,
0.4 mmol), Cp2TiCl2 (5 mol%), MeOLi (1.0 equiv, 0.2 mmol), neat
condition, 1008C, 24 h, yields of isolated products are given.
Bromides with electron-withdrawing groups such as -F,
-Cl as well as -CF3, and polyfluorinated bromobenzene also
proved to be no problems (6g–6k). Interestingly, even the
unprotected -NH2 and -NH groups that were supposed to
react with HBpin were also survived in our system (6m–6n).
In summary, we have developed an unprecedented
titanium-catalyzed boration of alkyl halides with pinacolbor-
ane and catecholborane to form synthetically useful alkyl
boronate esters. Our system can successfully suppress the
undesired hydrodehalogenation products that dominate when
using other transition-metal catalysts. Various primary, sec-
ondary, and tertiary bromides including other reducible ester,
alkenes and carbamate groups are readily borated and up to
95% yields of alkyl boronate esters are obtained. Moreover,
the titanium system also worked for other alkyl electrophiles
such as alkyl iodides, mesylates, and challenging unactivated
alkyl chlorides. Application to aryl bromides proved to be no
Scheme 3. Mechanism studies: Please see SI for details.
Furthermore, by adding 5,5-dimethyl-1-pyrroline N-oxide
(DMPO) (0.5 equiv) to the standard reaction solution, EPR
active signals were detected, which implies the formation of
4
www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
These are not the final page numbers!

Angewandte
Communications
Chemie
10630 – 10633; e) Y. Sasaki, Y. Horita, C. Zhong, M. Sawamura,
H. Ito, Angew. Chem. Int. Ed. 2011, 50, 2778 – 2782; Angew.
Chem. 2011, 123, 2830 – 2834.
problem as well. Preliminary mechanism studies revealed
a possible radical pathway and further efforts will be directed
toward a detailed understanding of the reaction mechanism.
[7] a) C.-T. Yang, Z.-Q. Zhang, H. Tajuddin, C.-C. Wu, J. Liang, J.-
H. Liu, Y. Fu, M. Czyzewska, P. G. Steel, T. B. Marder, L. Liu,
Angew. Chem. Int. Ed. 2012, 51, 528 – 532; Angew. Chem. 2012,
124, 543 – 547; b) H. Ito, K. Kubota, Org. Lett. 2012, 14, 890 –
893; c) H. Iwamoto, K. Kubota, E. Yamamoto, H. Ito, Chem.
Commun. 2015, 51, 9655 – 9658; d) S. K. Bose, S. Brand, H. O.
Omoregie, M. Haehnel, J. Maier, G. Bringmann, T. B. Marder,
ACS Catal. 2016, 6, 8332 – 8335; e) H. Iwamoto, K. Endo, Y.
Ozawa, Y. Watanabe, K. Kubota, T. Imamoto, H. Ito, Angew.
Chem. Int. Ed. 2019, 58, 11112 – 11117; Angew. Chem. 2019, 131,
11229 – 11234.
Acknowledgements
We are grateful to the National Natural Science Foundation
of China (91845108, 21901247, 21902167), Natural Science
Foundation of Jiangsu Province (BK20180246), and the
“Innovation & Entrepreneurship Talents Plan” of Jiangsu
Province for generous financial support. We would also like to
thank Prof. Chen Zhu and Dr. Xinxin Wu from Soochow
University for helping with EPR analysis.
[8] A. S. Dudnik, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 10693 –
10697.
[9] J. Yi, J.-H. Liu, J. Liang, J.-J. Dai, C.-T. Yang, Y. Fu, L. Liu, Adv.
Synth. Catal. 2012, 354, 1685 – 1691.
Conflict of interest
[10] a) T.-J. Gong, Y.-Y. Jiang, Y. Fu, Chin. Chem. Lett. 2014, 25, 397 –
400; b) P. K. Verma, K. S. Prasad, D. Varghese, K. Geetharani,
Org. Lett. 2020, 22, 1431 – 1436.
[11] S. K. Bose, K. Fucke, L. Liu, P. G. Steel, T. B. Marder, Angew.
Chem. Int. Ed. 2014, 53, 1799 – 1803; Angew. Chem. 2014, 126,
1829 – 1834.
[12] a) T. C. Atack, R. M. Lecker, S. P. Cook, J. Am. Chem. Soc. 2014,
136, 9521 – 9523; b) S. Wang, M. Sun, H. Zhang, J. Zhang, Y. He,
Z. Feng, CCS Chem. 2020, 2, 2164 – 2173.
The authors declare no conflict of interest.
Keywords: alkyl halides · boration · boronate ester ·
pinacolborane · titanium
[13] T. C. Atack, S. P. Cook, J. Am. Chem. Soc. 2016, 138, 6139 – 6142.
[14] X. Lu, Z.-Q. Zhang, L. Yu, B. Zhang, B. Wang, T.-J. Gong, C.-L.
Tian, B. Xiao, Y. Fu, Chin. J. Chem. 2019, 37, 11 – 18.
[15] Q. Liu, J. Hong, B. Sun, G. Bai, F. Li, G. Liu, Y. Yang, F. Mo, Org.
Lett. 2019, 21, 6597 – 6602.
[1] a) A. C. Frisch, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 674 –
688; Angew. Chem. 2005, 117, 680 – 695; b) A. Rudolph, M.
Lautens, Angew. Chem. Int. Ed. 2009, 48, 2656 – 2670; Angew.
Chem. 2009, 121, 2694 – 2708; c) Y. Lee, A. H. Hoveyda, J. Am.
Chem. Soc. 2009, 131, 3160 – 3161; d) R. Jana, T. P. Pathak, M. S.
Sigman, Chem. Rev. 2011, 111, 1417 – 1492; e) J. V. Obligacion,
P. J. Chirik, J. Am. Chem. Soc. 2013, 135, 19107 – 19110; f) J. Wu,
L. He, A. Noble, V. K. Aggarwal, J. Am. Chem. Soc. 2018, 140,
10700 – 10704; g) R. Oeschger, B. Su, I. Yu, C. Ehinger, E.
Romero, S. He, J. Hartwig, Science 2020, 368, 736 – 741.
[2] a) M. A. Beenen, C. An, J. A. Ellman, J. Am. Chem. Soc. 2008,
130, 6910 – 6911; b) L. J. Milo, J. H. Lai, W. Wu, Y. Liu, H. Maw,
Y. Li, Z. Jin, Y. Shu, S. E. Poplawski, Y. Wu, D. G. Sanford, J. L.
Sudmeier, W. W. Bachovchin, J. Med. Chem. 2011, 54, 4365 –
4377.
[16] a) Y. Cheng, C. Mꢁck-Lichtenfeld, A. Studer, Angew. Chem. Int.
Ed. 2018, 57, 16832 – 16836; Angew. Chem. 2018, 130, 17074 –
17078; b) D. Mazzarella, G. Magagnano, B. Schweitzer-Chaput,
P. Melchiorre, ACS Catal. 2019, 9, 5876 – 5880; c) L. Zhang, Z.-Q.
Wu, L. Jiao, Angew. Chem. Int. Ed. 2020, 59, 2095 – 2099; Angew.
Chem. 2020, 132, 2111 – 2115.
[17] Commercially available HBpin normally contains L·BH3 impur-
ity, for details of HBpin purification please see: S. Shimada, A. S.
Batsanov, J. A. K. Howard, T. B. Marder, Angew. Chem. Int. Ed.
2001, 40, 2168 – 2171; Angew. Chem. 2001, 113, 2226 – 2229.
[18] a) M. S. Viciu, G. A. Grasa, S. P. Nolan, Organometallics 2001,
20, 3607 – 3612; b) A. C. Bissember, A. Levina, G. C. Fu, J. Am.
Chem. Soc. 2012, 134, 14232 – 14237; c) S. Yow, S. J. Gates,
A. J. P. White, M. R. Crimmin, Angew. Chem. Int. Ed. 2012, 51,
12559 – 12563; Angew. Chem. 2012, 124, 12727 – 12731; d) N. A.
Isley, M. S. Hageman, B. H. Lipshutz, Green Chem. 2015, 17,
893 – 897; e) K. L. Bamford, S. S. Chitnis, Z.-W. Qu, D. W.
Stephan, Chem. Eur. J. 2018, 24, 16014 – 16018; f) Y.-J. Niu, G.-
H. Sui, H.-X. Zheng, X.-H. Shan, L. Tie, J.-L. Fu, J.-P. Qu, Y.-B.
Kang, J. Org. Chem. 2019, 84, 10805 – 10813.
[3] V. F. Hawkins, M. C. Wilkinson, M. Whiting, Org. Process Res.
Dev. 2008, 12, 1265 – 1268.
[4] a) D. A. Evans, G. C. Fu, A. H. Hoveyda, J. Am. Chem. Soc.
1992, 114, 6671 – 6679; b) S. Pereira, M. Srebnik, J. Am. Chem.
Soc. 1996, 118, 909 – 910; c) J. V. Obligacion, P. J. Chirik, Org.
Lett. 2013, 15, 2680 – 2683; d) M. L. Scheuermann, E. J. Johnson,
P. J. Chirik, Org. Lett. 2015, 17, 2716 – 2719; e) G. Wang, X.
Liang, L. Chen, Q. Gao, J.-G. Wang, P. Zhang, Q. Peng, S. Xu,
Angew. Chem. Int. Ed. 2019, 58, 8187 – 8191; Angew. Chem. 2019,
131, 8271 – 8275.
[5] a) K. M. Waltz, J. F. Hartwig, Science 1997, 277, 211 – 213; b) H.
Chen, S. Schlecht, T. C. Semple, J. F. Hartwig, Science 2000, 287,
1995 – 1997; c) I. A. Mkhalid, J. H. Barnard, T. B. Marder, J. M.
Murphy, J. F. Hartwig, Chem. Rev. 2010, 110, 890 – 931; d) S.
Kawamorita, R. Murakami, T. Iwai, M. Sawamura, J. Am. Chem.
Soc. 2013, 135, 2947 – 2950; e) X. Jia, Z. Huang, Nat. Chem. 2016,
8, 157 – 161; f) M. R. Jones, C. D. Fast, N. D. Schley, J. Am. Chem.
Soc. 2020, 142, 6488 – 6492; g) C. Shu, A. Noble, V. K. Aggarwal,
Nature 2020, 586, 714 – 719; h) R. L. Reyes, M. Sato, T. Iwai, K.
Suzuki, S. Maeda, M. Sawamura, Science 2020, 369, 970 – 974.
[6] a) S. Mun, J.-E. Lee, J. Yun, Org. Lett. 2006, 8, 4887 – 4889; b) J.-
E. Lee, J. Yun, Angew. Chem. Int. Ed. 2008, 47, 145 – 147; Angew.
Chem. 2008, 120, 151 – 153; c) K.-s. Lee, A. R. Zhugralin, A. H.
Hoveyda, J. Am. Chem. Soc. 2009, 131, 7253 – 7255; d) J. M.
OꢀBrien, K.-s. Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2010, 132,
[19] a) E. A. Bijpost, R. Duchateau, J. H. Teuben, J. Mol. Catal. A
Chem. 1995, 95, 121 – 128; b) N. Chinkov, A. Levin, I. Marek,
Angew. Chem. Int. Ed. 2006, 45, 465 – 468; Angew. Chem. 2006,
118, 479 – 482; c) A. Masarwa, D. Didier, T. Zabrodski, M.
Schinkel, L. Ackermann, I. Marek, Nature 2014, 505, 199; d) Y.-
Q. Zhang, E. Vogelsang, Z.-W. Qu, S. Grimme, A. Gansꢂuer,
Angew. Chem. Int. Ed. 2017, 56, 12654 – 12657; Angew. Chem.
2017, 129, 12828 – 12831; e) M. Reiß, F. Reiß, A. Spannenberg, P.
Arndt, T. Beweries, Organometallics 2018, 37, 4415 – 4423; f) C.
Yao, T. Dahmen, A. Gansꢂuer, J. Norton, Science 2019, 364,
764 – 767; g) X. Shi, S. Li, L. Wu, Angew. Chem. Int. Ed. 2019, 58,
16167 – 16171; Angew. Chem. 2019, 131, 16313 – 16317; h) U.
Rosenthal, Chem. Soc. Rev. 2020, 49, 2119 – 2139; i) C. Matt, C.
Kern, J. Streuff, ACS Catal. 2020, 10, 6409 – 6413; j) E. N.
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Bahena, S. E. Griffin, L. L. Schafer, J. Am. Chem. Soc. 2020, 142,
20566 – 20571.
Ishiyama, M. Murata, N. Miyaura, J. Org. Chem. 1995, 60, 7508 –
7510; b) M. Murata, S. Watanabe, Y. Masuda, J. Org. Chem.
1997, 62, 6458 – 6459; Cu: c) W. Zhu, D. Ma, Org. Lett. 2006, 8,
261 – 263; d) C. Kleeberg, L. Dang, Z. Lin, T. B. Marder, Angew.
Chem. Int. Ed. 2009, 48, 5350 – 5354; Angew. Chem. 2009, 121,
5454 – 5458; Ni: e) T. Yamamoto, T. Morita, J. Takagi, T.
Yamakawa, Org. Lett. 2011, 13, 5766 – 5769; f) J. Zhou, M. W.
Kuntze-Fechner, R. Bertermann, U. S. D. Paul, J. H. J. Berthel,
A. Friedrich, Z. Du, T. B. Marder, U. Radius, J. Am. Chem. Soc.
2016, 138, 5250 – 5253; Zn: g) S. K. Bose, A. Deißenberger, A.
Eichhorn, P. G. Steel, Z. Lin, T. B. Marder, Angew. Chem. Int.
Ed. 2015, 54, 11843 – 11847; Angew. Chem. 2015, 127, 12009 –
12014; Co: h) W. Yao, H. Fang, S. Peng, H. Wen, L. Zhang, A.
Hu, Z. Huang, Organometallics 2016, 35, 1559 – 1564; Fe: i) T.
Yoshida, L. Ilies, E. Nakamura, ACS Catal. 2017, 7, 3199 – 3203;
Photo-approach: j) K. Chen, S. Zhang, P. He, P. Li, Chem. Sci.
2016, 7, 3676 – 3680; Pyridine: k) L. Zhang, L. Jiao, J. Am. Chem.
Soc. 2017, 139, 607 – 610; Review: l) W. K. Chow, O. Y. Yuen,
P. Y. Choy, C. M. So, C. P. Lau, W. T. Wong, F. Y. Kwong, RSC
Adv. 2013, 3, 12518 – 12539.
[20] a) E. C. Ashby, W. S. Park, A. B. Goel, W. Y. Su, J. Org. Chem.
1985, 50, 5184 – 5193; b) M. Giedyk, R. Narobe, S. Weiß, D.
Touraud, W. Kunz, B. Kçnig, Nat. Catal. 2020, 3, 40 – 47.
[21] a) A. Gansꢂuer, B. Rinker, Titanium and Zirconium in Organic
Synthesis, Wiley-VCH, Weinheim, 2002, pp. 435 – 450; b) S. P.
Morcillo, D. Miguel, A. G. CampaÇa, L. ꢃlvarez de Cienfuegos,
J. Justicia, J. M. Cuerva, Org. Chem. Front. 2014, 1, 15 – 33; c) T.
McCallum, X. Wu, S. Lin, J. Org. Chem. 2019, 84, 14369 – 14380;
d) E. P. Beaumier, A. J. Pearce, X. Y. See, I. A. Tonks, Nat. Rev.
Chem. 2019, 3, 15 – 34; e) A. R. Martꢄnez, L. P. Morales, E. D.
Ojeda, M. C. Rodrꢄguez, I. Rodrꢄguez-Garcꢄa, J. Org. Chem.
2021, 86, 1311—1329; f) M. Manßen, L. L. Schafer, Chem. Soc.
Rev. 2020, 49, 6947 – 6994; g) Z. Zhang, T. Hilche, D. Slak, N. R.
Rietdijk, U. N. Oloyede, R. A. Flowers 2nd, A. Gansꢂuer,
Angew. Chem. Int. Ed. 2020, 59, 9355 – 9359; Angew. Chem.
2020, 132, 9441 – 9445.
[22] For more support for the formation of Cp2TiIIICl species, please
see supporting information Figure S7, S8.
[23] For previous report on Cp2TiIIICl species generation from
Cp2Ti(H)Cl please see: J. Gordon, S. Hildebrandt, K. R.
Dewese, S. Klare, A. Gansꢂuer, T. V. RajanBabu, W. A.
Nugent, Organometallics 2018, 37, 4801 – 4809. A proposed
reaction pathway is given in supporting information Scheme S4.
[24] Other catalysts/systems were known to be able to mediate the
boration of aryl halides, for selected examples see: Pd: a) T.
Manuscript received: January 13, 2021
Accepted manuscript online: February 19, 2021
Version of record online: && &&, &&&&
6
www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Boration
X. Wang, P. Cui, C. Xia,*
L. Wu*
&&&& — &&&&
Catalytic Boration of Alkyl Halides with
Borane without Hydrodehalogenation
Enabled by Titanium Catalyst
A general titanium-catalyzed boration of
alkyl (pseudo)halides with boranes is
reported. The system can successfully
suppress the undesired hydro-
dehalogenation process that prevails
using other transition-metal catalysts.
The current strategy worked for various
alkyl electrophiles, including unactivated
alkyl chlorides, with tolerance of reducing
functional groups such as ester, alkene,
and carbamate. Mechanistic studies
reveal a possible radical reaction pathway.
Angew. Chem. Int. Ed. 2021, 60, 1 – 7
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
7
These are not the final page numbers!