3-tert-Butyl-Substituted Cyclohexa-1,4-dienes as Isobutane Equivalents in the B(C6F5)3-Catalyzed Transfer Hydro-tert-Butylation of Alkenes

Article abstract of DOI:10.1002/chem.201604397

Cyclohexa-1,4-dienes with a tert-butyl group at C3 are shown to function as isobutane equivalents when activated by the strong boron Lewis acid tris(pentafluorophenyl)borane. The hitherto unprecedented transfer hydro-tert-butylation from one unsaturated hydrocarbon to another is achieved with 1,1-diarylalkenes as substrates, thereby presenting itself as a new way of incorporating tertiary alkyl groups into carbon frameworks. Transient carbocation intermediates give rise to competing reaction pathways that could not be fully suppressed.

Full text of DOI:10.1002/chem.201604397

DOI: 10.1002/chem.201604397
Communication
&
Hydroalkylation
3-tert-Butyl-Substituted Cyclohexa-1,4-dienes as Isobutane
Equivalents in the B(C6F5)3-Catalyzed Transfer Hydro-tert-
Butylation of Alkenes
Sebastian Keess and Martin Oestreich*[a]
Abstract: Cyclohexa-1,4-dienes with a tert-butyl group at
C3 are shown to function as isobutane equivalents when
activated by the strong boron Lewis acid tris(pentafluoro-
phenyl)borane. The hitherto unprecedented transfer
hydro-tert-butylation from one unsaturated hydrocarbon
to another is achieved with 1,1-diarylalkenes as substrates,
thereby presenting itself as a new way of incorporating
tertiary alkyl groups into carbon frameworks. Transient
carbocation intermediates give rise to competing reaction
pathways that could not be fully suppressed.
Scheme 1. Substituted cyclohexa-1,4-dienes as synthetic equivalents for hy-
drosilanes and dihydrogen (verified) and hydrocarbons (planned).
Si=RnH3ꢀnSi (n=0–3, R=aryl and/or alkyl). R1/R2 =H or Me. R3 =aryl or alkyl.
Our laboratory recently demonstrated that adequately substi-
tuted cyclohexa-1,4-dienes I and II serve as transfer reagents
for hydrosilanes[1] and dihydrogen,[2] respectively (Scheme 1,
top). The approach hinges on the ability of the strong Lewis
acid tris(pentafluorophenyl)borane, B(C6F5)3,[3] to abstract a hy-
dride from the bisallylic methylene group of these surroga-
tes,[1e,2b] forming Wheland intermediates either stabilized by
a silyl group (for I) or alkyl substituents (for II) along with boro-
Figure 1. Cylohexa-1,4-dienes 1–4 as isobutane equivalents.
hydride [HB(C6F5)3]ꢀ (not shown).[1e,2b] These eventually release
arenes, thereby enabling the (formal) transfer of hydrosilanes
or dihydrogen to C=C/CꢁC[1b–d,2b] as well as C=O/C=N[1c,2a]
cyclohexa-1,4-dienes 2–4 as potential transfer reagents
(Figure 1) and excluded parent 1[7] for its assumed tendency to
groups.
As part of this research program, we entertained the idea of
applying the above strategy to the transfer of hydrocarbons,
and surrogates III containing tertiary electrofuges Rtert seemed
particularly promising candidates (Scheme 1, bottom). We ex-
pected III to require additional substitution in the ipso position
to avoid competing proton release. Our plan was to realize the
hydro-tert-alkylation of alkenes, examples of which are exceed-
ingly rare.[4,5] The reaction will involve carbocations at the dif-
ferent stages of transfer process and is as such closely related
to the difficult Friedel–Crafts-type alkylation of alkenes.[6]
preferentially engage in transfer hydrogenation.[2b]
Transfer reagent 2 was readily obtained in one step by Birch
reductive alkylation of biphenyl (not shown).[8] We also pur-
sued the synthesis of surrogate 3 (Scheme 2) to replace diffi-
cult-to-remove biphenyl with toluene as the stoichiometric by-
product of the transfer hydro-tert-butylation. Birch reduction of
benzoate 5 and subsequent treatment with LiAlH4 yielded al-
cohol 6 (5!6, Scheme 2, top).[9] However, the deoxygenation
of 6 proved to be challenging (6!3). The delicate combina-
tion of steric hindrance (neopentylic primary alcohol) and elec-
tronic properties (bishomoallylic position of the hydroxy func-
tionality) creates this demanding setting (Scheme 2, bottom).
Transformation of 6 into the corresponding tosylate or mesy-
late was successful but no reactivity toward LiAlH4 was ob-
served (not shown). The more reactive triflate (not shown) as
well as phosphoramidate instantaneously rearranged to furnish
cycloheptatriene 7 (6!7).[10] A similar outcome was obtained
when using Et2SiH2 as the reductant in the presence of catalyt-
ic amounts of B(C6F5)3 (6!8).[11] Conversion of 6 to chloride 9
was achieved with SOCl2/pyridine (6!9) but reduction with
With the tert-butyl group as the archetypical tertiary electro-
fuge, we began to explore the transfer hydro-tert-butylation of
1,1-disubstituted alkenes catalyzed by B(C6F5)3. We envisaged
[a] S. Keess, Prof. Dr. M. Oestreich
Institut fꢀr Chemie, Technische Universitꢁt Berlin
Strasse des 17. Juni 115, 10623 Berlin (Germany)
E-mail: martin.oestreich@tu-berlin.de
Homepage: http://www.organometallics.tu-berlin.de
Supporting information and authors’ ORCIDs for this article are available
on the WWW under http://dx.doi.org/10.1002/chem.201604397.
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LiAlH4 failed again (not shown). Attempts to prepare the re-
spective bromide by the Appel reaction were again thwarted
by ring expansion. We finally succeeded in the “deoxygena-
tion” of the hydroxymethyl group in 6 by Corey–Kim oxidation
(6!10) followed by Wittig olefination (10!4). While 4 was
not what we had initially had in mind, we recognized 4 as an
attractive transfer reagent. The liberated styrene could under-
go cationic polymerization under the reaction setup of the
B(C6F5)3-catalyzed hydro-tert-butylation, thereby allowing for
facile separation of the stoichiometric byproduct.
Table 1. Optimization of the reaction conditions.
Entry Surrogate (equiv) Solvent
Conc. [M] Conv.[a] 12a/13a/14a[b]
1
2
3
4
5
6
7
2 (1.0)
2 (1.0)
2 (1.0)
2 (1.0)
2 (1.0)
2 (1.3)
2 (1.3)
2 (1.3)
2 (1.3)
1,2-F2C6H4 0.50
1,2-Cl2C6H4 0.50
98%
90%
traces n.d.
traces n.d.
50%
46%
96%
83:11:6
85:11:4
C6H6
n-pentane 0.50
CH2Cl2 0.50
0.50
53:24:23
64:20:16
87:10:3
1,2-F2C6H4 0.10
1,2-F2C6H4 0.50
1,2-F2C6H4 1.0
1,2-F2C6H4 0.50
1,2-F2C6H4 0.50
1,2-F2C6H4 0.50
1,2-F2C6H4 0.50
1,2-F2C6H4 0.50
1,2-F2C6H4 0.50
1,2-Cl2C6H4 0.50
8
9[c]
>99% 87:10:3
98%
67%
30%
>99% 51:34:15
>99% 89:9:2
>99% 58:35:7
>99% 58:40:2
11%
14%
97%
62%
>99% 57:41:2
>99% 60:38:2
>99% 57:41:2
85:11:4
85:10:5
78:14:8
10[d] 2 (1.3)
11[e] 2 (1.3)
12[f] 2 (1.3)
13[g] 2 (1.3)
14
15
16
17
18
19
20
21
4 (1.1)
4 (1.1)
4 (1.1)
4 (1.1)
4 (1.1)
4 (1.1)
4 (1.3)
4 (1.1)
C6H6
n-pentane 0.50
CH2Cl2 0.50
0.50
22:50:28
35:42:23
37:44:19
53:42:5
1,2-Cl2C6H4 0.10
1,2-Cl2C6H4 0.50
1,2-Cl2C6H4 1.0
1,2-Cl2C6H4 0.50
1,2-Cl2C6H4 0.50
1,2-Cl2C6H4 0.50
1,2-Cl2C6H4 0.50
22[c] 4 (1.1)
23[d] 4 (1.1)
24[f] 4 (1.1)
25[g] 4 (1.1)
95%
46%
89%
58:39:3
33:46:21
61:39 : <1
[a] Substrate conversion determined by GLC analysis using mesitylene as
internal standard. [b] Determined by 1H NMR analysis. [c] 10 mol%
B(C6F5)3 were used. [d] 2.5 mol% B(C6F5)3 were used. [e] 5.0 mol% B(4-
C6F4H)3 used as catalyst. [f] 1008C. [g] 08C. n.d.=not determined.
Scheme 2. Planned synthesis of transfer reagent 3 (top) and attempted de-
oxygenations of alcohol 6, eventually arriving at surrogate 4 (bottom).
KHMDS=potassium bis(trimethylsilyl)amide. DMPU=1,1-dimethyltetrahy-
dropyrimidin-2(1H)-one. NCS=N-chlorosuccinimide.
detected by 1H NMR spectroscopic or GLC analysis of the
crude reaction mixture. The involvement of carbenium ions in-
evitably led to side reactions, that is, the generation of byprod-
ucts 13 and 14 (Scheme 3). B(C6F5)3-triggered hydride abstrac-
tion from cyclohexa-1,4-dienes 2 or 4 affords ion pair IV. The
Wheland complex in IV can either transfer the tert-butyl cation
(IV!V, left cycle) or a distal proton (IV!VI, right cycle) to
alkene 11. In the latter case, formation of ion pair VI is accom-
panied by the stoichiometric release of isobutene, likely being
the driving force for this pathway. VI eventually collapses to
close the catalytic cycle, forming byproduct 13. Intermediate
V+ can either be directly reduced by the borohydride to fur-
nish the desired alkane 12 or can suffer b-elimination concomi-
tant with protonation of another molecule of substrate 11 to
yield byproducts 13 and 14 after hydride transfer. The observa-
tion that 13 and 14 are not formed in equimolar ratio shows
that both cycles are operative.
We then subjected both surrogates 2 and 4 to the typical
protocol of the alkene transfer hydrogenation[2b] with 1,1-di-
phenylethylene (11 a) as the model substrate and observed
quantitative conversion of 11 a after 24 or 16 h, respectively
(Table 1, entries 1 and 14). 1H NMR spectroscopic analysis of
the reaction mixtures showed that transfer of the tert-butyl
cation to alkene 11 a had indeed occurred,[12] and desired 12a
was formed predominantly in both cases (83% for 2 and 58%
for 4) along with 13a (11% for 2 and 35% for 4) and 14a (6%
for 2 and 7% for 4) as byproducts. This product distribution
emphasizes the effect of the R group in the ipso position on
the selectivity of this reaction. Isobutane surrogate 2 with
a phenyl group favors the formation of product 12a to a great-
er extent than 4 bearing a vinyl group in this position.[13]
Further attempts to improve the product distribution were
largely unsuccessful. The solvent had a pronounced effect (en-
tries 1–5 and 14–18) but the best selectivity and reactivity was
obtained in 1,2-F2C6H4 or 1,2-Cl2C6H4 (entries 1/2 and 14/15)
As anticipated for isobutane equivalent 4, the stoichiometric
byproduct styrene (16) polymerized as the monomer was not
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Scheme 4. Different 1,1-diarylalkenes for the isobutane transfer.
Scheme 3. Proposed catalytic cycle with pathways for the formation of by-
products 13 and 14.
We disclosed here a rare example of an alkene hydroalkyla-
tion involving carbocation intermediates.[4] The approach, that
is the formal transfer of isobutane from one unsaturated hy-
drocarbon to another, was in fact unprecedented before. How-
ever, the work is conceptual rather than synthetically useful at
this stage. The reagent preparation is challenging, and selectiv-
ity issues arising from the intermediacy of carbocations have
not been overcome yet. Nevertheless, the present hydro-tert-
butylation reveals itself as a new strategy to install tertiary
alkyl groups at an alkene terminus.
while other solvents such as C6H6, n-pentane, and CH2Cl2 led to
significantly lower conversions and selectivities (entries 3–5
and 16–18). A slight excess of 2 or 4 was beneficial in terms of
reaction rate but did not affect the selectivity (entries 7 and
20). A more dilute reaction mixture was detrimental, favoring
byproduct formation (entries 6 and 19). Conversely, higher con-
centration merely influenced the reaction rate (entries 8 and
21). We expected the concentration of the borohydride to
have an influence on the selective formation of 12a over 13a
and 14a. However, no effect was seen when using either 10 or Acknowledgements
2.5 mol% B(C6F5)3 (entries 9/10 and 22/23). Moreover, less
[14]
Lewis-acidic borane B(4-C6F4H)3
even led to a decreased
This research was supported by the Deutsche Forschungsge-
meinschaft (Oe 249/11-1). M.O. is indebted to the Einstein
Foundation (Berlin) for an endowed professorship.
amount of desired 12a (78%, entry 11 versus 87%, entry 7).
The borohydride emerging from B(4-C6F4H)3 is the slightly
better hydride donor than [HB(C6F5)3]ꢀ,[15] and that could have
favored reduction (V+!12) over b-elimination/proton transfer
(V+!14). Elevated reaction temperatures favored the forma-
tion of 13a (entries 12 and 24), and running the transfer
hydro-tert-butylation at 08C had no effect (entries 13 and 25).
We then compared 11 a with electronically modified 1,1-di-
arylalkenes 11 b and 11 c in the isobutane transfer (Scheme 4).
Both 11 b and 11 c with electron-withdrawing and -donating
substituents, respectively were also converted quantitatively
following the standard protocol. However, 11 c reacted signifi-
cantly less selective than parent 11 a, favoring transfer hydro-
genation over alkylation. Slightly better stabilization of inter-
mediate V+ reducing its hydride-accepting ability is likely to
account for this behavior. An electron-withdrawing substituent
as in 11 b turned out to be less problematic when reacted with
surrogate 2 but hydrogenation prevailed with 4. As for the re-
lated transfer hydrogenation,[2b] other alkene motifs such as a-
olefins, 1,2-disubstituted alkenes, a-alkyl-substituted styrenes
as well as trisubstituted alkenes resulted in intractable mix-
tures.
Keywords: alkenes · boron · carbocations · hydroalkylation ·
Lewis acids
[1] For a review of transfer hydrosilylation, see: a) M. Oestreich, Angew.
Chem. Int. Ed. 2016, 55, 494–499; Angew. Chem. 2016, 128, 504–509;
b) A. Simonneau, M. Oestreich, Angew. Chem. Int. Ed. 2013, 52, 11905–
11907; Angew. Chem. 2013, 125, 12121–12124; c) S. Keess, A. Simon-
neau, M. Oestreich, Organometallics 2015, 34, 790–799; d) A. Simon-
neau, M. Oestreich, Nat. Chem. 2015, 7, 816–822. For the quantum-
chemical analysis of the transfer hydrosilylation of alkenes, see: e) K.
Sakata, H. Fujimoto, Organometallics 2015, 34, 236–241.
[2] a) I. Chatterjee, M. Oestreich, Angew. Chem. Int. Ed. 2015, 54, 1965–
1968; Angew. Chem. 2015, 127, 1988–1991; b) I. Chatterjee, Z.-W. Qu, S.
Grimme, M. Oestreich, Angew. Chem. Int. Ed. 2015, 54, 12158–12162;
Angew. Chem. 2015, 127, 12326–12330 (including the quantum-chemi-
cal analysis of the alkene transfer hydrogenation).
[3] For a comprehensive review of B(C6F5)3-catalyzed SiꢀH and HꢀH bond
activation, see: M. Oestreich, J. Hermeke, J. Mohr, Chem. Soc. Rev. 2015,
44, 2202–2220.
[4] Lewis acid-catalyzed hydro-tert-butylation of alkenes with di-tert-butyl-
pyrocarbonate: U. Biermann, J. O. Metzger, J. Am. Chem. Soc. 2004, 126,
10319–10330.
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[5] Radical-chain hydro-tert-butylation of alkenes with tert-butylazodiphe-
nylcarbinol: D. W. K. Yeung, J. Warkentin, Can. J. Chem. 1976, 54, 1345–
1348.
[11] For the seminal report of the B(C6F5)3-catalyzed deoxygenation of alco-
hols with hydrosilanes, see: V. Gevorgyan, J.-X. Liu, M. Rubin, S. Benson,
Y. Yamamoto, Tetrahedron Lett. 1999, 40, 8919–8922.
[6] For a review of Friedel–Crafts-type alkene alkylation, see: a) H. Mayr,
Angew. Chem. Int. Ed. Engl. 1990, 29, 1371–1384; Angew. Chem. 1990,
102, 1415–1428; for seminal publications, see: b) G. A. Olah, S. J. Kuhn,
D. G. Barnes, J. Org. Chem. 1964, 29, 2685–2687; c) H. Mayr, W. Striepe,
J. Org. Chem. 1983, 48, 1159–1165.
[7] We nevertheless attempted to prepare 1 (pure compound unknown)
by reductive Birch alkylation of benzene without success.
[8] R. Lebeuf, J. Dunet, R. Beniazza, D. Ibrahim, G. Bose, M. Berlande, F.
Robert, Y. Landais, J. Org. Chem. 2009, 74, 6469–6478.
[12] It is important to note that B(C6F5)3 also promotes the degradation of
surrogate 2 in the absence of an alkene, albeit at dramatically reduced
rate (approximately 10% conversion after 24 h at room temperature).
[13] We also subjected 9 to our standard setup but neither tert-butyl-group
nor proton transfer to alkene 11 a was observed. Instead, 9 ring-ex-
panded to 7 and 8.
[14] For the relative Lewis acidity of B(4-C6F4H)3 compared to B(C6F5)3 deter-
mined by the Gutmann–Beckett method, see: M. Ullrich, A. J. Lough,
D. W. Stephan, J. Am. Chem. Soc. 2009, 131, 52–53.
[9] P. Tisselli, PhD thesis, King’s College London, United Kingdom, 2004.
[10] For early reports on related ring-expansion reactions of cyclohexa-1,4-
dienes, see: a) N. A. Nelson, J. H. Fassnacht, J. U. Piper, J. Am. Chem. Soc.
1959, 81, 5009; b) N. A. Nelson, J. H. Fassnacht, J. U. Piper, J. Am. Chem.
Soc. 1961, 83, 206–213.
[15] Z. M. Heiden, A. P. Lathem, Organometallics 2015, 34, 1818–1827.
Received: September 17, 2016
Published online on && &&, 0000
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COMMUNICATION
Jump! B(C6F5)3-triggered hydride ab-
straction from 3-tert-butyl-substituted
cyclohexa-1,4-dienes facilitates the
formal transfer of isobutane to 1,1-diar-
ylalkenes. Although side reactions of
the carbocation intermediates limit the
synthetic utility of this conceptually
new methodology, the present transfer
hydro-tert-butylation is a new way to in-
troduce tertiary alkyl groups into
carbon frameworks.
&
Hydroalkylation
S. Keess, M. Oestreich*
&& – &&
3-tert-Butyl-Substituted Cyclohexa-1,4-
dienes as Isobutane Equivalents in the
B(C6F5)3-Catalyzed Transfer Hydro-tert-
Butylation of Alkenes
Chem. Eur. J. 2016, 22, 1 – 5
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