Allylation of nitrosobenzene with pinacol allylboronates. A regioselective complement to peroxide oxidation

Article abstract of DOI:10.1021/ol101472k

Addition of nitrosobenzene to pinacol allylboronates leads to oxidation of the organoboron with concomitant rearrangement of the substrate alkene. This reaction appears to proceed by allylboration of the nitroso group in analogy to carbonyl and imine allylation reactions. Remarkably, the N-O bond is cleaved during the reaction such that simple alcohols are the final reaction product.

Full text of DOI:10.1021/ol101472k

ORGANIC
LETTERS
2010
Vol. 12, No. 17
3796-3799
Allylation of Nitrosobenzene with
Pinacol Allylboronates. A Regioselective
Complement to Peroxide Oxidation
Robert E. Kyne, Michael C. Ryan, Laura T. Kliman, and James P. Morken*
Department of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02467
morken@bc.edu
Received June 25, 2010
ABSTRACT
Addition of nitrosobenzene to pinacol allylboronates leads to oxidation of the organoboron with concomitant rearrangement of the substrate
alkene. This reaction appears to proceed by allylboration of the nitroso group in analogy to carbonyl and imine allylation reactions. Remarkably,
the N-O bond is cleaved during the reaction such that simple alcohols are the final reaction product.
Because of the utility of allylboron reagents in organic
synthesis, their preparation has been studied intensely.1 Along
these lines, recent efforts from our laboratory have focused
on the development of the catalytic hydroboration of dienes2
and the catalytic diboration of both allenes3 and dienes.4
These reactions convert simple hydrocarbon building blocks
into substituted pinacolato allylboronates. These types of
allylmetal reagents participate in a wide range of allylations
with carbonyl and imine derivatives.5 However, the only
other reactions that have been developed for these species
are a narrow range of oxidation,6 cross-coupling,7 conjugate
addition,8 and homologation reactions.9 To expand the utility
of allyl boronates in organic synthesis, we have begun to
study other reactions that might apply to these reagents.
Considering the isoelectronic relationship between the nitroso
group and carbonyl groups, we were prompted to study the
reaction between nitrosobenzene and allyl boronates. While
a single example by Bubnov describes the reaction between
nitrosobenzene and highly reactive triallyborane, a number
of critical issues remain unaddressed.10 First, it is not clear
whether the diminished electrophilicty of boronic esters
(5) For a review of allylboration of carbonyl compounds, see: Hall, D. G.
Pure Appl. Chem. 2008, 80, 913. See also: (b) Zhang, P.; Morken, J. P.
J. Am. Chem. Soc. 2009, 131, 12550. For the allylboration of imines, see:
(c) Sugiura, M.; Hirano, K.; Kobayashi, S. Org. Synth. 2006, 83, 170. (d)
Sieber, J. D.; Morken, J. P. J. Am. Chem. Soc. 2006, 128, 74. (e) Elford,
T. G.; Hall, D. G. Tetrahedron Lett. 2008, 49, 6995.
(1) For a recent review, see: Lachance, H.; Hall, D. G. In Organic
Reactions; Denmark, S. E., Ed.; Wiley: New York, 2009; Vol. 73.
(2) (a) Ely, R. J.; Morken, J. P. J. Am. Chem. Soc. 2010, 132, 2534.
See also: (b) Zaidlewicz, M.; Meller, J. Tetrahedron Lett. 1997, 38, 7279.
(c) Satoh, M.; Nomoto, Y.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1989,
30, 3789. (d) Matsumoto, Y.; Hayashi, T. Tetrahedron Lett. 1991, 32, 3387.
(e) Wu, J. Y.; Moreau, B.; Ritter, T. J. Am. Chem. Soc. 2009, 131, 12915.
(3) (a) Pelz, N. F.; Woodward, A. R.; Burks, H. E.; Sieber, J. D.; Morken,
J. P. J. Am. Chem. Soc. 2004, 126, 16328. (b) Burks, H. E.; Liu, S.; Morken,
J. P. J. Am. Chem. Soc. 2007, 129, 8766. See also: (c) Ishiyama, T.; Kitano,
T.; Miyaura, N. Tetrahedon Lett. 1998, 39, 2357. (d) Yang, F. Y.; Cheng,
C. H. J. Am. Chem. Soc. 2001, 123, 761.
(6) Review of oxidation of organoboron compounds: Brown, H. C.;
Snyder, C.; Rao, B. C. S.; Zweifel, G. Tetrahedron 1986, 42, 5505.
(7) Selected examples: (a) Nilsson, K.; Hallberg, A. Acta Chem. Scand.
B 1987, 41, 569. (b) Kalinin, V. N.; Denisov, F. S.; Bubnov, Y. N.
MendeleeV Commun. 1996, 206. (c) Kotha, S.; Behera, M.; Shah, V. R.
Synlett 2005, 12, 1877. (d) Yamamoto, Y.; Takada, S.; Miyaura, N. Chem.
Lett. 2006, 35, 704. (e) Kotha, S.; Shah, V. R.; Mandal, K. AdV. Synth.
Catal. 2007, 349, 1159. (f) Kotha, S.; Shah, V. R. Eur. J. Org. Chem. 2008,
6, 1054. (g) Gerbino, D. C.; Mandolesi, S. D.; Schmalz, H.; Podesta´, J. C.
Eur. J. Org. Chem. 2009, 23, 3964. (h) Flegeau, E. F.; Schneider, U.;
Kobayashi, S. Chem.sEur. J. 2009, 15, 12247.
(4) (a) Morgan, J. B.; Morken, J. P. Org. Lett. 2003, 5, 2573. (b) Burks,
H. E.; Kliman, L. T.; Morken, J. P. J. Am. Chem. Soc. 2009, 131, 9134.
See also: (c) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem. Commun.
1996, 2073. (d) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem. Commun.
1997, 689. (e) Clegg, W.; Thorsten, J.; Marder, T. B.; Norman, N. C.; Orpen,
A. G.; Peakman, T. M.; Quayle, M. J.; Rice, C. R.; Scott, A. J. J. Chem.
Soc., Dalton Trans. 1998, 1431.
(8) (a) Sieber, J. D.; Liu, S.; Morken, J. P. J. Am. Chem. Soc. 2007,
129, 2214. (b) Sieber, J. D.; Morken, J. P. J. Am. Chem. Soc. 2008, 130,
4978.
10.1021/ol101472k  2010 American Chemical Society
Published on Web 08/05/2010

relative to boranes will impede the reaction. Second, with
substituted allylic boronates, it is not readily apparent whether
the reaction with nitrosobenzene will occur with allylic
transposition as occurs with carbonyls or by coordination
and subsequent 1,2 alkyl migration as occurs in the reaction
between organoboranes and many reagents.11 Lastly, al-
though Bubnov has demonstrated that triallylborane and
nitrosobenzene react with relatively nonselective formation
of both N-O and C-O bonds, the issue of N- versus
O-allylation with allylic boronates was uncertain.12
pathway for allylic boronate 2 and nitrosobenzene occurs
by addition of the allylboron to the oxygen atom and with
allylic rearrangement.13
Considering the robustness of the N-O bond, it is
somewhat surprising that N-O bond-cleaved compound 3
is produced in eq 2 (Scheme 1). A clue to its formation can
be found in the fact that compound 5 is not isolated from eq
1 and that mass spectral analysis of the unpurified reaction
mixture from eq 2 revealed the presence of a compound with
1
Two preliminary experiments revealed much about the
reaction between allylboronates and nitrosobenzene. In the
first (eq 1, Scheme 1), 1,3-decadiene (1) was subjected to
an m/z ratio corresponding to compound 6 (Scheme 1). H
NMR analysis also reveals the presence of 6. In line with
these observations, it was surmised that a second molecule
of nitrosobenzene and the Brønsted base might conspire to
cleave the N-O bond of the initial allylation product in a
fashion such as that depicted in Scheme 2. This type of
Scheme 1. Reaction of Nitrosobenzene with Allylboronate 2
Scheme 2. Proposed Mechanism for N-O Bond Cleavage
Ni-catalyzed 1,4-hydroboration, a reaction that delivers cis
allyl boronate 2.2a After the reaction mixture was diluted
with THF, it was treated with 1.05 equiv of nitrosobenzene.
Subsequent oxidative treatment furnished allylic alcohols 3
and 4 in 44% and 23% yield, respectively. In the second
experiment (eq 2, Scheme 1), intermediate allyl boronate 2
was treated with nitrosobenzene for 13 h at -78 °C prior to
workup with brine and passage through a short silica gel
plug. This reaction did not provide any of the terminal
alcohol 4 but did produce internal allylic alcohol 3 and
alkoxyamine 5. The observation that allylic alcohol 4 is
produced only when oxidative workup is employed suggests
that 4 arises from unreacted 2. The observation that regioi-
somers 3 and 5, but not 4, are produced in the absence of
hydrogen peroxide suggests that the predominant reaction
reaction has been observed by Barbas and appears consistent
with the reaction outcome.14,15
In view of the mechanism depicted in Scheme 2, it might
be anticipated that additional nitrosobenzene and alternate
bases would provide an improved yield of allylation product
3. As depicted in Table 1 (entry 1), addition of 3 equiv of
Table 1. Tandem Diene Hydroboration/Nitrosobenzene
Oxidation
(9) Homologation of allyl boronates: (a) Hoffmann, R. W.; Stiasny, H. C.
Tetrahedron Lett. 1995, 36, 4595. (b) Matteson, D. S.; Majumdar, D. J. Am.
Chem. Soc. 1980, 102, 7588. (c) Matteson, D. S.; Majumdar, D. J.
Organomet. Chem. 1980, 184, C41. (d) Stymiest, J. L.; Bagutski, V.; French,
R. M.; Aggarwal, V. K. Nature 2008, 456, 778. (e) Bagutski, V.; Ros, A.;
Aggarwal, V. K. Tetrahedron 2009, 65, 9956.
entry
base
% yielda
1
2
3
4
5
6
7
NaOH/H2O2
NaOH
none
CsOH
LiOH
69
61
37
55
62
59
67
(10) Bubnov, Y. N.; Pershin, D. G.; Karionova, A. L.; Gurskii, M. E.
MendeleeV Commun. 2002, 12, 202.
(11) (a) Brown, H. C.; Singaram, B. Pure Appl. Chem. 1987, 59, 879.
(b) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 24, 4695.
(12) For recent examples that use PhNO as an electrophile, see: (a)
Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2003, 125, 6038. (b)
Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2003, 125, 10808. (c) Yamamoto, Y.; Momiyama, N.;
Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5962. (d) Momiyama, N.;
Yamamoto, H. J. Am. Chem. Soc. 2005, 127, 1080. (e) Simmons, B.; Walji,
A. M.; MacMillan, D. W. C. Angew. Chem., Int. Ed. 2009, 48, 4349.
KOH
NH4OH
a Isolated yield of purified product.
Org. Lett., Vol. 12, No. 17, 2010
3797

is significantly diminished (entry 3). With the requirement
for addition of H2O2 apparently obviated, we examined
workup under basic, nonoxidative conditions. As depicted
in Table 1, a number of bases suffice for the nitrosobenzene-
mediated oxidation of allylboronates. In all cases reasonable
yields of secondary allylic alcohol 3 were isolated.
Table 2. Substrate Scope for Tandem Diene Hydroboration/
Oxidation
To study the generality of the nitrosobenzene-mediated
allylboronate oxidation, a number of substrates were explored
in the tandem hydroboration/oxidation sequence, and both
nitrosobenzene/NH4OH (method A) and NaOH/H2O2 (method
B) oxidation procedures were examined. As depicted in Table
2, a number of different terminally substituted butadienes
participate in the reaction and deliver moderate yields of the
secondary allylic alcohol from method A. Whereas protected
oxygen functional groups (entries 3, 5-7) and steric en-
cumbrance (entries 2 and 5) at the diene terminus are
tolerated, substitution at the 2 position of the diene leads to
substantially diminished reactivity (entry 8). As noted in
Table 2, oxidation with H2O2/NaOH consistently delivers
the terminal allylic alcohol 4. The fact that method B is
efficient with all substrates in Table 2 suggests that the
diminished reactivity observed with method A in entry 8
arises due to inefficient reaction of the intermediate allylic
boronate with nitrosobenzene. Surprisingly, substitution at
the 3 position is tolerated in the nitrosobenzene reaction, and
the derived tertiary alcohol was isolated in good yield (entry
9).
With achiral allylboronates such as 2 the nitrosobenzene
oxidation products 3 are racemic. However, stereogenicity
in the allylic boronate may impact the oxidation if the
reacting alkene is prochiral. To study the capacity for
diastereoinduction in the nitrosobenzene-mediated oxidation
reaction, the chiral 1,4-diboryl-2-alkene 7 (Scheme 3) was
Scheme 3
.
Diastereoinduction in the Oxidation of Chiral
Allylboronate 6
a Isolated yield of purified product. Value is an average of two
experiments.
nitrosobenzene, as opposed to 1 equiv (Scheme 1), results
in a significantly enhanced yield of the secondary allylic
alcohol 3, and with oxidative workup, none of the terminal
allylic alcohol 4 could be detected. According to the
mechanism in Scheme 2, hydrogen peroxide is not required
for the reaction, and the experiment in entry 2 (Table 1) bears
this out. In the absence of base, however, the reaction yield
(13) The N-allylation product was not detected in these reactions. This
observation is in contrast to that of Bubnov,10 who notes that a 2:1 mixture
of O-allylation and N-allylation products is obtained from nitrosobenzene
and triallylborane. In the reaction of tricrotylborane, Bubnov also notes
allylic rearrangement.
(14) (a) Ramachary, D. B.; Barbas, C. F., III. Org. Lett. 2005, 7, 1577.
See also: (b) Becker, A. R.; Sternson, L. A. J. Org. Chem. 1980, 45, 1708.
(15) Bubnov also notes N-O bond cleavage but claims a different
mechanism that is light-promoted. We find that the reactions of allyl
boronates proceed equally well in the dark.
generated by Ni-catalyzed diene diboration and subjected to
the nitrosobenzene allylation reaction. Whereas reaction with
nitrosobenzene at room temperature delivered diol 8 in 2.6:1
diastereoselection (data not shown), when nitrosobenzene
was added to diboronate 7 at -78 °C and followed by
oxidative workup, diol 8 was isolated in 10:1 anti:syn
stereoselection and in moderate yield (eq 3, Scheme 3). For
3798
Org. Lett., Vol. 12, No. 17, 2010

comparison, the direct oxidation with hydrogen peroxide
furnishes regioisomeric 1,4-diol 9 in 85% yield (eq 4).
the reaction. Similar features account for the stereochemistry
of hydroboration of allylic silanes and boranes.16
In conclusion, treatment of simple allylboronates with
nitrosobenzene and base can be considered a reliable strategy
for oxidation with allylic rearrangement. Future studies will
expand upon this reactivity pattern and will be reported in
due course.
The fact that the allylation of nitrosobenzene proceeds with
allylic rearrangement suggests that a cyclic transition struc-
ture operates. This hypothesis was further supported by
subjecting octylB(pin) to nitrosobenzene and NH4OH; less
than 5% of 1-octanol could be detected. With these observa-
tions in mind, the stereochemical outcome of the reaction
depicted in eq 3 may be rationalized by considering transition
structure 10 as the predominating reaction pathway. Presum-
ably, the enhanced basicity of nitrogen relative to oxygen
results in N-B bonded complex 10 wherein nitrosobenzene
has coordinated to the least hindered boronate. The stereo-
genic carbon atom in transition structure 10 is oriented in a
manner where the electron-rich C-B bond is aligned with
the π-system of the reacting alkene in a manner that should
enhance π nucleophilicity. If the small hydrogen is placed
inside with respect to the alkene to minimize A[1,3] strain,
the model correctly predicts the stereochemical outcome of
Acknowledgment. This work was supported by the NIH
(GM 59417). We thank BASF for a generous donation of
pinacolborane.
Supporting Information Available: Complete experi-
mental procedures and characterization data (1H and 13C
NMR, IR, and mass spectrometry). This material is free of
charge via the Internet at http://pubs.acs.org.
OL101472K
(16) (a) Fleming, I.; Lawrence, N. J. J. Chem. Soc., Perkin Trans. 1
1992, 24, 3309. (b) Fleming, I.; Lawrence, N. J. Tetrahedron Lett. 1988,
29, 2073. (c) Fleming, I.; Lawrence, N. J. Tetrahedron Lett. 1988, 29, 2077.
(d) Pelz, N. F.; Morken, J. P. Org. Lett. 2006, 8, 4557.
Org. Lett., Vol. 12, No. 17, 2010
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