Synthesis of tert-butyl peroxyacetals from benzyl, allyl, or propargyl ethers via iron-promoted C-H bond functionalization

Article abstract of DOI:10.1002/adsc.201200410

When benzyl, allyl, and propargyl ethers were treated with tert-butyl hydroperoxide and a catalytic amount of iron(III) acetylacetonate, tert-butyl peroxyacetals were produced in good to excellent yields, via C-H bond functionalization. This method is also applicable to ethylene acetals of unsaturated aldehydes to give peroxyorthoesters.

Full text of DOI:10.1002/adsc.201200410

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DOI: 10.1002/adsc.201200410
Synthesis of tert-Butyl Peroxyacetals from Benzyl, Allyl,
À
or Propargyl Ethers via Iron-Promoted C H Bond
Functionalization
Satoshi Iwata,a Takeshi Hata,a and Hirokazu Urabea,*
a
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of
Technology, 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan
Fax : (+81)-(0)45-924-5849; e-mail: hurabe@bio.titech.ac.jp
Received: May 9, 2012; Revised: August 10, 2012; Published online: November 21, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200410.
Abstract: When benzyl, allyl, and propargyl ethers
were treated with tert-butyl hydroperoxide and
a catalytic amount of ironACTHNURGTNE(UNG III) acetylacetonate, tert-
butyl peroxyacetals were produced in good to excel-
À
lent yields, via C H bond functionalization. This
method is also applicable to ethylene acetals of un-
saturated aldehydes to give peroxyorthoesters.
À
Scheme 1. Addition of different nucleophiles.
Keywords: tert-butyl hydroperoxide; C H function-
alization; iron; oxidation; peroxyacetals; peroxyor-
thoesters
When benzyl butyl ether (1) was treated with t-
BuO2H in the presence of various transition metal
salts (entries 1–8, Table 1), ester 3 was a major prod-
uct as expected from the precedents.[3c–f,4a–c,5g–j,6] How-
À
3
À
Direct functionalization of the sp -C H bond, which ever, we found that the C H bond functionalization
[1,7]
refers to substitution of an existing hydrogen with with Fe
A
accompanied the uptake of a t-
À
a heteroatom group, has attracted much attention re- BuO2 residue to the substrate, giving mixed peroxy-
cently.[1,2] This has been usually performed by the oxi-
acetal 2[4d] in good yield, which is the product of the
ACHTUNGTRENNUNG
À
dative cleavage of a C H bond to give a carbocation aforementioned path b in Scheme 1 and is otherwise
in the presence of a nucleophile and is facilitated by tedious to prepare (entries 9 and 10).[8,9] After further
an activator such as transition metal catalysts as optimization as shown in entries 11–18, the best result
shown in Eq. (1). Although a variety of nucleophiles was achieved with FeACTHUNRGTNEUNG(acac)3 (10 mol%) and molecular
sieves (entry 16). Under these conditions, the yield of
by-product 3 was kept as low as possible. While the
decomposition of primary product 2 to ester 3 ap-
pears to be a major side path as described above, the
formation of a tert-butyl acetal arising from reduced t-
BuOH was negligible under these conditions. The re-
action could proceed without a metal salt, but the
are applied to this process, it has not been amply ex- product yields remained low (entries 19 and 20). The
plored that the oxidant itself is incorporated into the iron catalyst appears to serve for shortening the reac-
substrate to give a synthetically useful product. We tion period, which in turn minimizes the chance of de-
report here an example of the latter case, where t- composition of produced 2 to 3 during the reaction.
À
BuO2H plays a dual role as an oxidant of the C H The molecular sieves should keep the system anhy-
bond in benzyl ethers and a nucleophile as shown in drous, otherwise water may cleave the tert-butyl per-
path b of Scheme 1,[3,4] which is in contrast to the oxide bond to give the more labile hydroperoxide
aforementioned reactions of the externally added re- amenable to collapse to esters. This is consistent with
agents (path a).[4,5]
the fact that sterically demanding benzyl ethers tend
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Adv. Synth. Catal. 2012, 354, 3480 – 3484

Synthesis of tert-Butyl Peroxyacetals from Benzyl, Allyl, or Propargyl Ethers
Table 1. Optimization of reaction conditions for the prepara-
tion of peroxyacetal 2.
Table 2. Synthesis of various tert-butyl peroxyacetals.
[a]
This reaction is also valid for a cyclic ether to give
14[4a,b] in good yield.
Abbreviation + or - shows the presence or absence of
molecular sieves.
Yields were determined by H NMR spectroscopy using
[b]
1
A proposed mechanism of this reaction is shown in
Scheme 2.[10,11] The initiation step to generate t-BuO2C
may start efficiently in the presence of iron salt. This
process is followed by the generation of benzyl radical
15, which is transmitted to benzyl cation 16 and t-
BuOC under the iron catalysis to continue the propa-
gation step. As a result, one equiv. of t-BuO2H is con-
an internal standard. Isolated yield is in parentheses.
t-BuO2H (3–3.6 equiv.) was used.
Reaction period was extended to 6 h.
[c]
[d]
to show better yields in this reaction, which will be sumed as an oxidant (to release t-BuOH and H2O)
discussed later. and one more as a nucleophile. This radical mecha-
This preparation of peroxyacetals from benzyl nism was evidenced by the fact that the addition of
ethers appears reasonably general, as shown in galvinoxyl apparently suppressed the progress of reac-
Table 2. Although the undesired esters were formed tion [Eq. (2)]. As suggested from the data of Table 1,
in small amounts in most cases, they were readily sep- the reaction does not necessarily need the iron salt
arated by routine flash chromatography on silica gel. and could proceed by the thermal decomposition of t-
An electron-withdrawing substituent on the aromatic BuO2H itself, but this is likely facilitated by the iron
ring decreased the product yields (see products 7–9) salt as shown in Scheme 2. The higher nucleophilici-
due to the enhanced production of the corresponding ty[12] and lower steric hindrance of t-BuO2H than t-
ester. The ortho substituents did not block the reac- BuOH should account for the exclusive incorporation
tion (products 4, 5, and 12). Furthermore, it is inter- of the former in the presence of the latter, especially
esting to note that sterically hindered benzyl tert-butyl at the late stage of reaction.
ethers gave the desired products 11–13 in better
The above mechanism suggests that a radical- or
yields than the corresponding n-butyl ethers (2, 5, and cation-stabilized group in place of the aromatic ring
6). This may come from the steric protection of the would enable the similar reaction. This was soon
peroxy moiety against the attack of other molecules. found to be true, as allyl and propargyl ethers 17 and
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Satoshi Iwata et al.
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Scheme 2. Proposed reaction course.
19 underwent the same reaction to give olefinic and
acetylenic peroxyacetals 18 and 20, respectively, in
synthetically acceptable yields [Eq. (3) and Eq. (4)],
showing that this reaction is quite simple and useful
as a new synthetic method. In addition, unsaturated
acetals 21–25 were found to be good substrates for
this transformation to afford peroxyorthoesters 26[4e]
30 in excellent yields [Eq. (5), Eq. (6) and Eq. (7)].
–
In conclusion, various tert-butyl peroxyacetals,
which are otherwise tedious to obtain, were readily
prepared from benzyl ethers, t-BuO2H, and a catalytic
amount of FeACHTUNGTRENNUNG(acac)3 in good to excellent yields. This
method is also valid for the preparation of olefinic
and acetylenic tert-butyl peroxyacetals and unsaturat-
ed peroxyorthoesters. Further investigations on the
extension of this reaction and synthetic applications
of the resultant peroxyacetals[13–15] are in progress in
our laboratory.
Experimental Section
Typical Procedure for the Preparation of
Peroxyacetals: Butyl (tert-
Butylperoxy)ACHTUNGTRENNUNG(phenyl)methyl Ether (2)
Caution: Although we have not encountered any dangerous
situation during this study, due care must be taken in han-
dling peroxy compounds particularly in a large-scale prepa-
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Synthesis of tert-Butyl Peroxyacetals from Benzyl, Allyl, or Propargyl Ethers
ration. tert-Butyl hydroperoxide in decane should be trans-
ferred with a plastic pipette.
To a suspension of benzyl butyl ether (1) (32.8 mg,
documented. Under Fe catalysis: a) T. Nagano, S. Ko-
bayashi, Chem. Lett. 2008, 37, 1042–1043. Rh: b) A. J.
Catino, J. M. Nichols, H. Choi, S. Gottipamula, M. P.
Doyle, Org. Lett. 2005, 7, 5167–5170. Metal-free: c) J.
Zhang, Z. Wang, Y. Wang, C. Wan, X. Zheng, Z. Wang,
Green Chem. 2009, 11, 1973–1978; d) M. Ochiai, T. Ito,
H. Takahashi, A. Nakanishi, M. Toyonari, T. Sueda, S.
Goto, M. Shiro, J. Am. Chem. Soc. 1996, 118, 7716–
7730; e) T. Sueda, S. Fukuda, M. Ochiai, Org. Lett.
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0.200 mmol), FeACHTUNGTRENNUNG(acac)3 (7.1 mg, 0.020 mmol), and MS 4ꢁ
(100 mg) in 1.0 mL of CH3CN was added tert-butyl hydro-
peroxide (0.20 mL, 5.0–6.0M solution in decane, ca. 1.0–
1.2 mmol) by a plastic pipette at room temperature under
argon. The mixture was stirred in an oil bath maintained at
808C for 3 h. After being cooled to room temperature, the
reaction mixture was filtered through a short pad of silica
gel with the aid of ethyl acetate. The combined filtrates
were concentrated under vacuum to give a crude oil,
1H NMR analysis of which revealed that the yields of the
title compound, butyl benzoate (3) as a by-product, and re-
covered starting material 1 are 79%, 17%, and 4%, respec-
tively, by using trichloroethylene as an internal standard.
The crude oil was chromatographed on silica gel (hexane-
ethyl acetate) to afford the title compound as an oil; yield:
40.0 mg (79%).
À
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search (B) (21350027) and a Grant-in-Aid for Young Scien-
tists (B) (23750102, to T. H.) from JSPS, Japan.
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also likely as shown below. In this mechanism, t-BuOC
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[15] Attempted deprotection of the acetal unit of 26 with
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