An example of overriding cyanation during reaction of a primary alcohol with o-nitrophenyl selenocyanate

Article abstract of DOI:10.3987/com-06-s(k)12

The first example of a nitrile as the end product of a Mitsunobu substitution involving o-nitrophenyl selenocyanate and tributylphosphine is reported. Neighboring group participation operates and leads favorably to competitive formation of a 2-cyanotetrah

Full text of DOI:10.3987/com-06-s(k)12

HETEROCYCLES, Vol. 72, 2007
111
HETEROCYCLES, Vol. 72, 2007, pp. 111 - 114. © The Japan Institute of Heterocyclic Chemistry
Received, 27th October, 2006, Accepted, 18th December, 2006, Published online, 19th December, 2006. COM-06-S(K)12
AN EXAMPLE OF OVERRIDING CYANATION DURING REACTION OF A
‡
PRIMARY ALCOHOL WITH o-NITROPHENYL SELENOCYANATE
Shuzhi Dong and Leo A. Paquette*
Evans Chemical Laboratories, The Ohio State University, Columbus, OH 43210,
USA; e-mail: paquette.1@osu.edu
Abstract – The first example of a nitrile as the end product of a Mitsunobu
substitution involving o-nitrophenyl selenocyanate and tributylphosphine is
reported. Neighboring group participation operates and leads favorably to
competitive
formation
of
a
2-cyanotetrahydrofuran.
We recently described a useful variant of the zirconocene-promoted vinylfuranoside ring contraction1
wherein an asymmetric route to highly-functionalized cyclobutanes was realized.2 The objective of this
study was to explore the possibility of extending this unique chemistry to the synthesis of pestalotiopsin
A (1).3,4 We envisioned that the successful early construction of intermediate (3)5 might provide a
workable pathway via 2 ultimately to this bioactive target (Scheme 1).
Scheme 1
AcO
O
O
HO
O
OPMB
OH
O
OMOM
OMe
H
TBSO
H
H
RO
H
OH
OMe
2
3
1
__________
‡
This paper is dedicated to Professor Yoshito Kishi, a friend and colleague responsible for many elegant
accomplishments in synthetic organic chemistry.

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HETEROCYCLES, Vol. 72, 2007
In order to test the feasibility of this concept, 3 was transformed over several steps into hydroxy lactone
(4).6 The unreactivity of the hydroxyl functionality in 4 was soon recognized. This inertness, which is
attributed to the heightened level of steric congestion in the proximate vicinity, caused us not to be
concerned with a protection strategy en route to 6 (Scheme 2).
Scheme 2
O
O
O
OPMB
OPMB
OH
O
OH
O
DDQ, CH2Cl2
O
O
H
H
pH 7 buffer
(90%)
H
H
HO
H
HO
H
HO
OH
OH
OM e
OM e
5
OMe
O3, CH2Cl2
-78 oC; Ph3P
(9 9%)
6
4
OsO4, NMO, py
THF, pH 7 buffer
(99%)
10% TFA,
CH2Cl2, rt
(89%)
OH
OH
O
O
OH
NaIO4, THF
O
O
O
OPMB
OPMB
OPMB
pH 7 buffer
(84%)
O
H
O
O
H
H
H
HO
H
HO
H
HO
OPMB
OH
OM e
OMe
OMe
8
7
6'
The shorter of two pathways from 4 to this triol entailed removal of the pair of PMB groups to provide 5
and subsequent ozonolytic cleavage of its double bond. Alternatively, application of the Johnson-
Lemieux protocol resulted in arrival at keto lactone (8) in advance of the dual deprotection step.7 The
availability of 6, whose complex 1H NMR spectrum indicated the existence of an equilibrium with 6', was
projected to allow serial application of the Mitsunobu aryl selenylation with o-nitrophenyl selenocyanate
(5.0 equiv) and tributylphosphine (5.0 equiv), and subsequent Grieco olefination upon exposure to
hydrogen peroxide.8 The first of these steps relies on the transient intervention of intermediates
generalized by 9 and 10 (Eq. 1). In light of the high nucleophilicity of selenium anions in SN2 reactions
of primary oxaphosphonium salts such as 10, alkyl aryl selenides have been isolated uniquely from these
reactions in high yield (Eq. 2).9 In the specific case of 11, however, activation of the "upper" CH2OH
group in this manner is met with competitive neighboring group participation, giving rise to oxonium ion
(12). Subsequent nucleophilic attack by the sterically less demanding cyanide ion leads to 14 as the
major end product.10,11
Bu3P
RCH2OH
RCH2OPBu3
ArSe
ArSeCN
ArSePBu3 CN
HCN
(1)
(2)
9
10
CN
ArSe
RCH2Se Ar
RCH2CN
10

HETEROCYCLES, Vol. 72, 2007
113
The R-configurational assignment accorded the newly introduced anomeric center in 14 and its congeners
is based on the anticipated lower enthalpy arising from the endo-anomeric effect, in addition to dipole
moment and steric considerations.12
Scheme 3
NO2
SeCN
O
O
O
CN
O
O
O
OPBu3
SeAr
O
O
O
Bu3P, THF
H
H
H
H
HO
H
HO
H
HO
SeAr
Se Ar
OMe
OMe
OMe
14 (53%)
11
12
NO2
H2O2, THF
(99%)
SeCN,
Bu3P, THF
O
O
O
CN
O
O
O
SeAr
O
O
O
H2O2, THF
(99%)
H
H
H
H
HO
H
H
HO
SeAr
HO
OMe
OMe
13 (20%)
OM e
16
15
Selenoxide eliminations applied to 13 and 14 led to 15 and 16, respectively. Once the terminal double
bond had been introduced as in 16, the remaining hydroxyl group participates readily in a spontaneous
elimination reaction to deliver 17 (Scheme 4). Also, the unprecedented diversion associated with the
formation of nitrile (14) can be redirected simply by making alternate recourse to acetonide (18). Its
efficient conversion to 19 provides added support for the likely intervention of oxonium ion (12). This
mechanistic pathway may serve as the basis of a cyclizative synthetic approach to 2-
cyanotetrahydrofurans.13
Scheme 4
O
O
NO2
SeCN
NO2
SeCN
O
O
O
CN
O
O
O
SeAr
SeAr
OH
16
O
O
O
Bu3P, THF
(90%)
Bu3P, THF
(75%)
H
H
H
H
HO
H
HO
OH
OMe
OM e
18
OMe
19
17

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HETEROCYCLES, Vol. 72, 2007
ACKNOWLEDGEMENT
We thank The Ohio State University for the award of a Presidential Fellowship to S. D. and for partial
financial support.
REFERENCES AND NOTES
1.
2.
3.
Review: L. A. Paquette, J. Organomet. Chem., 2006, 691, 2083.
S. Dong, G. D. Parker, T. Tei, and L. A. Paquette, Org. Lett., 2006, 8, 2429.
Isolation: (a) M. Pulici, F. Sugawara, H. Koshino, G. Okada, Y. Esumi, J. Uzawa, and S. Yoshida,
Phytochemistry, 1997, 46, 313. (b) M. Pulici, F. Sugawara, H. Koshino, J. Uzawa, S. Yoshida, E.
Lobkovsky, and J. Clardy, J. Org. Chem., 1996, 61, 2122.
4.
Alternate synthetic approaches to 1: (a) D. Johnston, E. Couché, D. J. Edmonds, K. W. Muir, and
D. J. Procter, Org. Biomol. Chem. 2003, 328. (b) D. J. Edmonds, K. W. Muir, and D. J. Procter, J.
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Tetrahedron Lett., 2005, 46, 5815.
5.
6.
7.
8.
9.
Compound (3) is a diastereomer of 21 reported in reference 2.
S. Dong, Ph.D. Dissertation, The Ohio State University, 2007.
L. Yan and D. Kahne, Synlett., 1995, 523.
P. A. Grieco, S. Gilman, and M. Nishizawa, J. Org. Chem., 1976, 41, 1485.
For recent examples, consult: (a) T. Yoshimitsu, S. Sasaki, Y. Arano, and H. Nagaoka, J. Org.
Chem., 2004, 69, 9262. (b) M. Uyanik, H. Ishibashi, K. Ishihara, and H. Yamamoto, Org. Lett.,
2005, 7, 1601.
10. The Mitsunobu aryl selenylation of 6 likely proceeds via the hydroxy ketone form because the
significant steric shielding present in 6' is expected to preclude activation by tributylphosphine.
11. A referee has offered an alternative mechanism for consideration. In this view, CN anion attacks
stereoselectively the keto carbonyl in the oxophosphonium intermediate (11), which follows an
internal attack of the resulting oxy anion on the terminal methylene bearing the oxophosphonium
group leading to 14. However, in our opinion, intramolecular neighboring group participation
should be kinetically advantaged leading to 12 as a more probable intermediate. If the
intermolecular process were to dominate, the CN anion would be forced to attack the less hindered
terminal methylene bearing the oxophosphonium group preferably, rather than the unactivated
carbonyl group.
12. H. Booth, J. M. Dixon, and K. A. Khedhair, Tetrahedron, 1992, 48, 6161.
13. M. T. Reetz, J. Chatziiosifidis, H. Künzer, and H. Müller-Starke, Tetrahedron, 1983, 39, 961.