Regioselective insertion of carborynes into ethereal C-H bond: Facile synthesis of α-carboranylated ethers

Article abstract of DOI:10.1021/ja201126h

Carborynes can exist in two resonance forms, bonding form vs biradical form. The biradical form can be readily generated via the elimination of LiI from 1-iodo-n-lithio-1,n-C₂B₁₀H₁₀ (n = 2, 7) under UV irradiation. They ca

Full text of DOI:10.1021/ja201126h

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Regioselective Insertion of Carborynes into Ethereal CꢀH Bond: Facile
Synthesis of r-Carboranylated Ethers
Sunewang R. Wang, Zaozao Qiu, and Zuowei Xie*
Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, New Territories,
Hong Kong, China
S Supporting Information
b
insight into the reaction, a UVꢀvisible absorption spectrum of
the reaction solution was obtained.12 It was found that the
ABSTRACT: Carborynes can exist in two resonance forms,
bonding form vs biradical form. The biradical form can be
readily generated via the elimination of LiI from 1-iodo-n-
lithio-1,n-C2B10H10 (n = 2, 7) under UV irradiation. They
can undergo R-CꢀH bond insertion with aliphatic ethers,
affording R-carboranylated ethers in excellent regioselec-
tivity at room temperature. This serves as a new methodol-
ogy for the generation of a series of functionalized
carboranes bearing alkoxy units.
solution exhibited three major absorption bands: a very strong
absorption near 230 nm, a strong absorption near 280 nm, and a
mediate absorption near 350 nm, all of which were in UV region.
Thus, it is rational to assume that a small amount of UV light
emitted from the fluorescent lamps may play an important role in
this process.13 The higher yields obtained from the reactions
under UV irradiation (365 or 254 nm) also supported this
assumption (Table 1, entries 5 and 6).14 It was noteworthy that
1-Br-2-Li-1,2-C2B10H10 was stable for 24 h in Et2O at room
temperature under UV irradiation (Table 1, entry 7).12
Direct R-carboranylation of various ethers with o-carboryne
3a was explored (Table 2). Similar to diethyl ether 5a, symme-
trical primary ethers 5bꢀd also worked well with decreased
yields from the Et to n-Bu group, which may be caused by the
increasing steric hindrance of ethers (Table 2, entries 1ꢀ3). Such
steric effect was also reflected on the regioselectivity in the
reaction of unsymmetrical primary ether 5d. It was noted that
yields obtained from reactions under UV irradiation were higher
than those under fluorescent light irradiation. For unsymmetrical
n-butyl methyl ether 5e, an evident preference for secondary
CꢀH bond cleavage over methyl CꢀH bond cleavage was
observed (Table 2, entry 5). It is consistent with the stability
of the resulting ethereal radicals.2a,d,15 Similar regioselectivity
trend was also found in the reaction of DME 5f. Notably, 1,2-
disubstituted carboranes 8af were isolated in 15% yield (Table 2,
entry 6). In the case of methyl tert-butyl ether 5g, UV irradiation
was necessary to accelerate the reaction and to increase the yield
(Table 2, entry 7). No productive results were obtained for ethers
containing secondary alkyl groups (Table 2, entries 8 and 9). o-
Carborane was predominantly regenerated when 2a was com-
pletely consumed in these ethers. For cyclic ethers, the reaction
was much dependent on the ring size due to steric effects
(Table 2, entries 10ꢀ12).15 For example, a good total yield
was obtained for THF 5j in both conditions, but only 23% and
5% of desired products were isolated, respectively, for THP 5k
and 1,4-dioxane 5l even under UV irradiation. Similar to 5f, 1,2-
disubstituted carboranes 8aj were also isolated with a meso:rac
ratio of 44:56. In contrast, the precursor 2a was stable at room
temperature in anisole, the semiaromatic ether, under UV
irradiation.
elective radical cleavage of relatively unreactive CꢀH bonds
S
has received considerable attention from the chemical com-
munity due to increasing interest in CꢀH bond
functionalization.1ꢀ4 Ethers are among the most attractive sub-
strates for this purpose because of the susceptibility to hydrogen
abstraction of their R-CꢀH bonds, which makes the regioselec-
tive chemical transformations possible.2 o-Carboryne (1,2-dehy-
dro-o-carborane) (3a), a very reactive intermediate reported first
in 1990,5 reacts readily with alkenes, dienes, alkynes, benzene or
polycyclic aromatics in [2 þ 2], [4 þ 2] cycloaddition and ene-
reaction patterns,6 similar to that of benzyne.7 It can be generated
in situ from either 1-Br-2-Li-1,2-C2B10H105 or 1-Me3Si-2-[IPh-
(OAc)]-1,2-C2B10H10.8 Recently, we reported a more efficient
precursor 1-I-2-Li-1,2-C2B10H10 (2a), readily prepared from o-
carborane (1a), for the production of 3a.9a,10 Our previous work
showed that o-carboryne can formally insert into the CꢀC bond
of aromatic rings bearing alkoxy groups to form cyclooctatetrae-
nocarboranes 4 (Scheme 1).10 However, the substrate anisoles
were employed as solvent in the reactions. In the search for an
appropriate solvent for such reactions, R-carboranylated ether
6aa was unprecedentedly isolated in very high yield when the
reaction was carried out in diethyl ether. It seems that o-
carboryne favors insertion into the ethereal R-CꢀH bond rather
than the CꢀO bond, in a different manner from that of benzyne
(Scheme 1).11 These new findings are reported in this
communication.
Treatment of 2a with anisole in diethyl ether at 60 °C over-
night gave, after workup, only the unexpected CꢀH bond
1
insertion product 6aa as shown by H NMR and GCꢀMS
analyses. In the absence of anisole, the reaction also proceeded
very well, affording 6aa at 60 °C or even at rt in 80% isolated yield
(Table 1, entries 1, 2). Surprisingly, when the reaction was
performed in the dark, the consumption of 2a in diethyl ether
was dramatically suppressed and the reaction was incomplete in
24 h at rt or even 60 °C (Table 1, entries 3 and 4). To gain some
Cage B-substituents such as phenyl, halo, and methyl
groups were well tolerated for this reaction (Table 3). Two
Received: February 4, 2011
Published: March 09, 2011
r
2011 American Chemical Society
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|

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Scheme 1. Reaction of Reactive Intermediates with Ethers
Table 2. Reaction of Ethers with o-Carborynea
Table 1. Screening of Reaction Conditions
entry
condition
6aa (%)a
1
2
3
4
5
6
7c
fluorescent lamp, 60 °C
fluorescent lamp, rt
in the dark, rt
80
80
12 (2)b
35 (6)b
85
a FL stands for fluorescent lamp; UVL stands for UV lamp (365 nm).
b For yield of each isomer, see SI. c meso:rac = 44:56.
in the dark, 60 °C
UV lamp (365 nm), rt
UV lamp (254 nm), rt
UV lamp (365 nm), rt
common nucleophilic reactions. Meanwhile, the intermolecular
primary kinetic isotope effect (KIE) experiments were also
carried out under standard conditions (eq 2).12
85
N. R.
a Isolated yield. Yield in parentheses refers to 7aa. b 2a was not
completely consumed. c Replacement of 2a by its bromo analogue.
diastereoisomers were formed in a 1:1 ratio for 3-substituted
carboranes (entries 1ꢀ2). It is noted that electronic factor plays
an evident role in the regioselectivity for 9-substituted carboranes
in view of the results from entries 3 and 4.16 Electronic effects also
show dramatic influence on the product yields. For example,
4,5,7,8,9,10,11,12-octamethyl carboranylated ether 6ha was iso-
lated in as low as 35% yield, while 9,12-dimethyl carboranylated
ether 6ga was obtained in an excellent yield.
The results showed a kH/kD value of 5.3. Such a significant
isotope effect revealed that the CꢀH bond cleavage was the rate-
determining step.2e,f Competitive experiments in a mixed solvent
of diethyl ether and toluene (1:1 in v/v) afforded the CꢀH bond
insertion product 6aa in 81% yield, and no [4 þ 2] cycloaddition
products were detected.12 This result indicated that o-carboryne
3a generated herein might not exist as the bonding form but
rather as a biradical form, which prefers hydrogen abstraction
instead of cycloaddition (Scheme 2).
To gain some insight into the reaction pathway, a radical
scavenger, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), was
added to the reaction system (eq 1).
On the basis of the above experimental results, a plausible
mechanism is proposed in Scheme 2. UV irradiation promotes
the elimination of LiI from 2a giving the reactive intermediate o-
carboryne 3a that is best described as a resonance hybrid of both
bonding and biradical forms. Such intermediate undergoes
hydrogen abstraction (HA) with 5a to generate radicals I and
II, which is the rate-determining step. A following fast single-
electron transfer (SET) between I and II produces carboranyl
anion III and electrophile IV. Finally, the nucleophilic addition of
III to IV yields the desired insertion product 6aa.
Not only was the formation of the desired product 6aa
completely suppressed, but also the iodo anion 2a itself was
surprisingly stabilized by TEMPO. This result suggested that a
radical process was possibly involved in the initial step of the
reaction. The aforementioned positive correlation between the
nucleophilicity of the cage carbon and the observed regioselec-
tivity (Table 3, entries 3 and 4) is in agreement with that found in
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Table 3. Effects of Cage B-Substituents on r-
Carboranylation
biradical form, affording R-carboranylated ethers with excellent
regioselectivity. This serves as a new methodology for the
generation of a series of functionalized carboranes bearing
alkoxy units.
’ ASSOCIATED CONTENT
S
Supporting Information. Detailed experimental proce-
b
dures, complete characterization data, and X-ray data in CIF
format for (R,R)-6ba, m-6fa, and meso-8aj. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
zxie@cuhk.edu.hk
’ ACKNOWLEDGMENT
This work was supported by grants from the Research Grants
Council of the Hong Kong Special Administration Region
(Project No. 404610), Direct Grant (Project No. 2060407),
and The Chinese University of Hong Kong.
Scheme 2. Possible Pathway for Direct R-Carboranylation of
Ethers
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