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Synthesis of Aryl Trimethylstannane via BF3·OEt2-mediated Cross-Coupling of Hexaalkyl Distannane Reagent with Aryl Triazene at Room Temperature Shuai Mao, Zhengkai Chen, Lu Wang, Daulat Bikram Khadka, Minhang Xin, Pengfei Li, and San-Qi Zhang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02766 • Publication Date (Web): 12 Dec 2018 Downloaded from http://pubs.acs.org on December 16, 2018
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The Journal of Organic Chemistry
Synthesis
of
Aryl
BF3·OEt2-mediated
Trimethylstannane
Cross-Coupling
of
via
Hexaalkyl
Distannane Reagent with Aryl Triazene at Room Temperature Shuai Mao,†,# Zhengkai Chen,‡,# Lu Wang,† Daulat Bikram Khadka,§ Minhang Xin,† Pengfei Li,*,‖ and San-Qi Zhang*,† †Department
of Medicinal Chemistry, School of Pharmacy, Xi’an Jiaotong University, Xi’an 710061, China.
‡Department
of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, China.
ǁFrontier
Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710054, China.
§Department
of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA
N R1
Het
N
N
+
BF3 (SnMe3)2
Readily Acessible Reagents Broad Substrate Scope Insensitive to Air and Moisture Scale Up
OEt
R2 2
R1 Het
SnMe3
R = alkyl, halo, ester,aryl, amino... 26 examples
in 45-72% isolate yields
[Pd] Ar'Br R1 Symmetrical and unsymmetrical biaryls
ABSTRACT: BF3·OEt2-mediated cross-coupling of (SnMe3)2 with aryl triazene offers a new strategy for the synthesis of aryl stannane. A variety of synthetically useful aryl trimethylstannanes were produced in moderate to good yields with this metal-free approach. One-pot sequential Stille cross-coupling with different aryl bromides provides a short entry to both symmetrical and unsymmetrical biaryl compounds.
Considering the great importance of well-known Stille coupling reaction in the formation of C–C bond, the rapid assembly of organotin reagents has attracted considerable interest among the organic chemists.1 Apart from the construction of C–
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C bond, the organotin reagents can also be applied in other useful transformation.2 The conventional methods to access aryl stannane compounds mainly rely on the reaction of air and moisture sensitive aryl-metal reagents with trialkyl tin chloride, under harsh reaction conditions.3 In this aspect, transition metal-catalyzed stannylation of aryl halides which possesses tremendous versatility and functional group compatibility is a more reliable route.4 Remarkably, this methodology has been recently expanded to include a C–H bond activation strategy and significant progress has been achieved.5 However, transition metal catalysts are expensive and sometimes sometimes result into metal contaminants in the final products. Thus, more attention was beginning to shift to the transition-metal free process in organic synthesis. Recently, stannylation of arylamine via oxidative deamination by alkylnitrite has been reported.6 It provides a direct conversion of arylamine to aryl stannanes under metal-free conditions which is an innovative development in aryl stannanes synthesis. More recently, our group reported an efficient metalcatalyst-free approach to synthesize trimethylarylstannanes from aryl halides promoted by UV light.7 However, given the great importance of aryl stannanes and the limited number of available synthetic methods, the development of novel and practical methods to access these compounds is still highly desirable. Aryl triazenes are an important class of molecules that have drawn a lot of attention from the organic chemists.8 Owing to the low cost and easy availability of aryl triazenes, C–N electrophiles have emerged as powerful alternatives to aryl halides as coupling partners in the cross-coupling arena. In the last two decades,
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The Journal of Organic Chemistry
aryltriazene has been used as equiverlant of aryldiazonium salt in the presence of Lewis or Brønsted acid in nucleophilic substitution reactions and transition metals-catalyzed coupling reactions.9 In particular, BF3·OEt2 has proven to be an efficient reagent to activate aryltriazene in Pd-catalyzed Suzuki-Miyaura coupling reaction.10 Although the use of triazane as a coupling partner in coupling reaction has increased, only aryl triazenes substituted with electron-donating groups can be subjected
to
a
coupling
reaction
efficiently;
aryl
triazenes
with
the
electron-withdrawing group usually give poor yields10a,10b. In comparison, Stille coupling reaction represents one of the most reliable methods in syntheses of complex molecules where great substrate compatibility, mild reaction conditions and good yields have been the main features. Moreover, in the transition metal-catalyzed cross-coupling reactions, aryltriazenes usually behave only as the electrophile instead of a nucleophile. Therefore, effective transformation of aryltriazenes to aryl stannanes could facilitate the targeted coupling reactions by overcoming the limitations associated with aryl triazenes.” In this context, we demonstrate a BF3·OEt2-mediated deaminostannylation of a series of functionalized aryl triazenes for the assembly of corresponding aryl stannane derivatives. This method may potentially have wide application in combinatorial chemistry. We commenced the investigation by choosing aryl triazene 1a with (SnMe3)2 (1,1,1,2,2,2-hexamethyldistannane) as model substrates to optimize the reaction conditions. The reaction was conducted by the employment of BF3·OEt2 as additive in EtOH at room temperature (rt) under air (Table 1, entry 1). To our delight, the reaction
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Table 1 Optimization of reaction conditionsa N N N
EtO2C
+
(SnMe3)2
additive solvent, temp, time
EtO2C 2a
1a
entry
additive
solvent
temp
time
(°C)
(min)
(equiv)
a
Sn
yieldb (%)
1
BF3·OEt2 (1.0)
EtOH
rt
60
34
2c
BF3·OEt2 (1.0)
Dioxane
rt
60
trace
3
BF3·OEt2 (1.0)
DME
rt
60
26
4
BF3·OEt2 (1.0)
THF
rt
60
23
5
BF3·OEt2 (1.0)
DMF
rt
60
trace
6
BF3·OEt2 (1.0)
DMSO
rt
60
trace
7
BF3·OEt2 (1.0)
CH2Cl2
rt
60
30
8
BF3·OEt2 (1.0)
Toluene
rt
60
19
9
BF3·OEt2 (1.0)
CH3CN
rt
30
67
10
BF3·OEt2 (1.0)
CH3CN
40
10
59
11
BF3·OEt2 (1.0)
CH3CN
0
90
68
12
BF3·OEt2 (1.0)
CH3CN
-10
180
65
13d
Other acids (1.0)
CH3CN
rt
60
