Electronically promoted Payne rearrangement of 3-CF3-2,3- epoxyalcohols

Article abstract of DOI:10.1021/ol048229x

(Chemical Equation Presented) Smooth and selective Payne rearrangement was achieved for the above types of epoxyalcohols with a CF₃ group so as to form thermodynamically more stable alkoxides, where the strongly electron-withdrawing nature of this moiety played a significantly important role and was proved to overcome increased steric instability of epoxides from syn-E to anti-Z isomers.

Full text of DOI:10.1021/ol048229x

ORGANIC
LETTERS
2004
Vol. 6, No. 22
4073-4076
Electronically Promoted Payne
Rearrangement of
3-CF3-2,3-Epoxyalcohols
Takashi Yamazaki,*,† Tatsuro Ichige, and Tomoya Kitazume
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho,
Midori-ku, Yokohama 226-8501, Japan
tyamazak@cc.tuat.ac.jp
Received September 2, 2004
ABSTRACT
Smooth and selective Payne rearrangement was achieved for the above types of epoxyalcohols with a CF3 group so as to form thermodynamically
more stable alkoxides, where the strongly electron-withdrawing nature of this moiety played a significantly important role and was proved to
overcome increased steric instability of epoxides from syn-E to anti-Z isomers.
Payne rearrangement1 is known as the base-catalyzed migra-
tion of 2,3-epoxyalcohols proceeding with inversion of
stereochemistry at the 2 position and is a well-documented
and widely used synthetic tool for the construction of tar-
get materials.2 However, formation of an isomeric epoxy-
alcohol mixture caused a significant problem because, for
example, the subsequent oxirane ring opening by appro-
priate nucleophilic species at the 2 position should furnish
epimeric materials. For this reason, it is a crucial issue for
synthetic chemists to properly control such a thermodynamic
equilibrium.
electron-withdrawing CF3 group promoted the migration of
a TBS moiety employed for the hydroxy protection, which
effectively facilitated the troublesome and lengthy protec-
tion-deprotection processes. Scheme 1 shows a typical ex-
Scheme 1
ample:4 independent subjection of monosilylated diols 1 and
2 to the described basic condition yielded essentially the same
1:2 mixture ratio, which was rationalized as follows. In this
sequence, stabilization of the resultant alkoxide directly
obtained from 2 should be more pronounced than the one
(1) Hanson, R. M. Org. React. 2002, 60, 1.
During the course of our synthetic study of sugars tri-
fluorinated at the 6 position,3 we have found that the strongly
(2) (a) Prasit, P.; Robertson, G.; Rokach, J. Carbohydr. Res. 1990, 202,
93. (b) Wrobel, J. E.; Ganem, B. J. Org. Chem. 1983, 48, 3761.
(3) (a) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org. Chem. 1993,
58, 4346. (b) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org. Chem. 1995,
60, 6046.
† Current address: Department of Applied Chemistry, Tokyo University
of Agriculture and Technology, 2-24-16 Nakamachi, Koganei 184-8588,
Japan.
(4) Yamazaki, T.; Oniki, T.; Kitazume, T. Tetrahedron 1996, 52, 11753.
10.1021/ol048229x CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/08/2004

from 1 because of the strongly inductive electron-withdrawal
by the CF3 group, which overwhelmed the undesired steric
congestion occurring in 2 and, as a result, moved the equi-
librium toward the right to produce the sterically more
crowded but electronically more stabilized compound 2.5
This basic information in hand, we have devised a uti-
lization of this anion-stabilizing ability to the Payne rear-
rangement of 3-CF3-2,3-epoxyalcohols6 which led to the
anticipation of a single product due to the expected strong
equilibrium preference between two isomeric materials. In
this communication we describe our preliminary results on
this topic, realizing the efficient stereodivergent construction
of regioisomeric target epoxyalcohols from a single R,â-
unsaturated ketone by way of this unique pathway as the
key step.
agents: in the case of R ) PhCH2CH2-, DIBAL-H furnished
the syn isomer in a stereoselective fashion by way of an
acyclic Felkin-Anh type of transition state (92% syn),
whereas intramolecular chelation led to predominant forma-
tion of E-anti-6 when the NaBH4-ZnI2 system9 was em-
ployed (90% anti). The results from four types of substrates
(a-d as shown in Scheme 2) were collected in Table 1. As
Table 1. Preparation of E-4, E-5, and E-6
isolated yield (%)
R
4a
5
E-syn -6b
E-a n ti-6b
a
b
c
d
PhCH2CH2
n-C6H13
Ph
96
84
91
88
61
47
69c
53d
91 (92:8)
97 (10:90)
83 (11:89)
90 (14:86)
67 (5:95)
90 (88:12)
90 (46:54)
96 (17:83)
The requisite diastereomeric starting materials E-syn- and
E-anti-6 were stereoselectively prepared as shown in Scheme
2. Allylic alcohols E-4, obtained by condensation of in situ
PhCH2C(CH3)2
a Total yield from 2-bromo-3,3,3-trifluoropropene. b In the parenthesis
are shown the syn:anti ratios. c Epoxidation was carried out at -30 °C for
2 h. d Epoxidation was carried out at -30 °C to rt for 6 h.
Scheme 2 a
reported previously, 4 was obtained in excellent yields, and
the two-step sequence to 5 was performed in about 80% for
each transformation, resulting in moderate yields.
We next tried to find appropriate reaction conditions for
Payne rearrangement using E-syn-6a as the representa-
tive substrate. Treatment of this compound by NaH in THF
at 0 °C led to production of the desired rearranged product
Z-anti-7a in only 49% yield along with 50% of the
unexpected â-hydroxy carboxylic acid 8 (Scheme 3). The
a Reagents and conditions: (a) 2 equiv LDA/THF, -78 °C, 5
min. (b) RCHO, -78 °C, 30 min. (c) Red-Al/toluene, -78 °C, 3
h. (d) PDC, Ac2O/CH2Cl2, reflux 1 h. (e) Urea-H2O2, DBU/THF,
-30 °C, 6 h. f) DIBAL-H/THF, -78 °C, 1 h. (g) NaBH4-ZnI2/
CH2Cl2, -78 to -10 °C, 6 h. a: R ) PhCH2CH2. b: R ) n-C6H13.
c: R ) Ph. d: R ) PhCH2C(CH3)2.
Scheme 3
generated 3,3,3-trifluoropropynyllithium and appropriate
aldehydes, followed by the Red-Al reduction,3b were trans-
formed into enones that were then reacted with UHP (urea
hydrogen peroxide) in the presence of DBU7 to furnish
epoxyketone E-5. This is the route of choice because the
direct electrophilic epoxidation of E-4 was found to be diffi-
cult because of the attachment of the strongly electron-with-
drawing CF3 group to the π-system, effectively decreasing
the electron density as well as the HOMO energy level8
which resulted in lower nucleophilicity. Epoxyalcohols E-6
were obtained by the judicious choice of the reducing
latter might be formed by the 1,2-hydride shift of the
epoxyalkoxide followed by release of the CF3 group from
the resultant hydroxyketone.10 Because activation of the
intermediate by the intramolecular chelation of sodium cation
is assumed to be responsible for the formation of this by-
product, we tried to change this coordination circumstance.
It is noteworthy that addition of 5 equiv of HMPA sig-
nificantly affected the present reaction, leading to completion
of isomerization from E-syn-6a to Z-anti-7a in only 3 h at
ambient temperature in 96% yield.
(5) In TBS migration from secondary to secondary hydroxyl groups,
perfect regioselectivity was obtained.
(6) Payne rearrangement of the CF3-containing materials was previously
reported: von dem Bussche-Hu¨nnefeld, C.; Seebach, D. Chem. Ber. 1992,
125, 1273.
This rearrangement is quite unique for the following two
reasons: (1) in general, Payne rearrangement proceeds
(7) Allen, J. V.; Bergeron, S.; Griffiths, M. J.; Mukherjee, S.; Roberts,
S. M.; Williamson, N. M.; Wu, L. E. J. Chem. Soc., Perkin Trans. 1 1998,
3171-3180.
(8) Shinohara, N.; Haga, J.; Yamazaki, T.; Kitazume, T.; Nakamura, S.
J. Org. Chem. 1995, 60, 4363.
(9) Fustero, S.; Pina, B.; Torre, M. G.; Navarro, A.; Arellano, C. R.;
Simon, A. Org. Lett. 1999, 1, 977.
(10) Hydrolytic removal of a CF3 group was previously reported:
Delgado, A.; Clardy, J. Tetrahedron Lett. 1992, 33, 2789.
4074
Org. Lett., Vol. 6, No. 22, 2004

smoothly in an aqueous media and there have been relatively
few examples occurring in aprotic solvents, and (2) as is
understood readily, E-syn-6a is a very rare substrate to be
exclusively converted to the isomeric Z-anti-7a with an
apparently sterically less stable cis epoxy function. Thus,
the energetic difference of sodium alkoxides from E-syn-6a
and Z-anti-7a would be large enough to compensate for such
a steric disadvantage.
For confirmation of generality of this electronically pro-
moted Payne rearrangement, other E-syn- and -anti-6 were
employed as substrates. As shown in Table 2, stereospecific
Table 2. Payne Rearrangements of E-syn- and -anti-6
Next, ab initio computation (B3LYP/6-31+G*) of the
model compounds was carried out11 to clarify, from the
theoretical point of view, if this assumption was the case
(Scheme 4). For convenience of calculation, the actual
substrate syn:anti
product
yielda (%) selectivityb (%)
Scheme 4
E-syn -6a
E-a n ti-6a
E-syn -6b
E-a n ti-6b
E-syn -6cc
E-a n ti-6c
E-syn -6d
E-a n ti-6d
92:8
Z-a n ti-7a
E-a n ti-7a
Z-a n ti-7b
E-a n ti-7b
Z-a n ti-7c
E-a n ti-7c
Z-a n ti-7d
E-a n ti-7d
96
91
94
96
88d
91d
29e
81
92
90
91
89
99
90
83
98
10:90
88:12
11:89
99:1
14:86
17:83
5:95
a Isolated yield unless otherwise noted. b Selectivity of the major isomer.
c Recrystalized material was used. d 3 equiv of EtOH was added. e Yield
was determined by 19F NMR.
Payne rearrangement was attained with excellent isolated
yields irrespective of the original stereochemistry of sub-
strates employed. Epoxyalcohols E-syn- or -anti-6 were
proved to follow extremely smooth rearrangement: facile
interconversion of E-anti-6 to E-anti-7 was readily under-
stood by the fact that this process did not require any
significant change in steric hindrance, and more importantly,
even E-syn-6 was smoothly transformed into the sterically
less favorable Z-anti-7. E-syn-6c was the special case;
subjection of NaH led to formation of a structurally unknown
byproduct to some extent, and modulation of the reactivity
was realized when NaOEt, generated in situ by use of 1.2
equiv of NaH and 3 equiv of EtOH, was used. The low yield
of E-syn-6d would result from exceeding the steric repulsive
interaction between the epoxy moiety and the quaternary
center next to the OH-attached carbon atom when the
intramolecular SN2 ring opening was about to occur. The
relative stereochemistry was determined by the reductive ring
opening of 6 and 7.14 For example, E-syn-6a and its
rearranged isomer Z-anti-7a possessing a PhCH2CH2 group
as R were independently subjected to a THF solution
containing Red-Al to exclusively furnish the same 1,3-diol,
syn-8a, in excellent yields without any sign of the regioi-
someric 1,2-diol formation. Isolation of the diastereomeric
anti-8a was also attained by application of the same
procedure for both E-anti-6a and E-anti-7a. These 1,3-diols
8a were then transformed into the corresponding acetonides
countercation, sodium, was replaced by lithium. Four isomers
with two types of substituents R were compared, whose
energy differences wearere shown in Scheme 4.12 In con-
sideration of equiriburium between E-anti-EA1 and -EA2,
the energetic preference expects predominance of the latter
(R ) H) and such tendency is significantly pronounced when
R ) Li, allowing us to anticipate quite smooth conversion
to E-anti-EA2. On the other hand, epoxyalcohol E-syn-EA1
is 1.8 kcal/mol more stable than its isomer, Z-anti-EA2,
but their alkoxide forms exhibit the opposite trend and
Z-anti-EA2 becomes 5.5 kcal/mol more stable despite the
sterically less favorable cis epoxide structure. Thus, the
energetic preferences obtained by ab initio molecular orbital
calculations correctly anticipates the preferred compound in
equilibrium, as well as the relative reaction rate.13
(11) Computation was carried out by Gaussian W03, version 6.0. Frisch,
M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A.; Vreven, T.; Kudin, K. N.; Burant, J.
C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.;
Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.;
Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain,
M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski,
J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,
W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian, Inc.: Pittsburgh,
PA, 2003.
1
syn- and anti-9a by the routine method. Close H NMR
(13) When following the reaction by 19F NMR (NaH/THF in the absence
of HMPA), complete Payne rearrangement was observed for E-anti-6a in
5 h, but more than 10 h was required for E-syn-6a.
(12) Interaction between R (H or Li) and epoxy oxygen was found in
all the isomers obtained.
(14) Ma´lek, J. Org. React. 1985, 34, 1.
Org. Lett., Vol. 6, No. 22, 2004
4075

as well as the stereostructure of 7 after Payne rearrangement.
This assignment was also consistent with the result of 13C
NMR on the basis of Rychnovsky’s report:15 chemical shifts
of the two methyl groups of acetonides were statistically
almost similar (usually <2 ppm) for 1,3-anti forms, but more
than 10 ppm difference was noticed for the corresponding
1,3-syn counterparts. In our instance, ∆δ values were
calculated to be 0.04 and 9.82 ppm for anti- and syn-9a,
respectively.
Scheme 5. Reductive Epoxide Ring Opening of 6 and 7 and
Acetonide Formation of the Resultant 1,3-Diols 8a
In conclusion, we have successfully established the extra-
ordinarily facile electronically controlled Payne rearrange-
ment of 3-CF3-2,3-epoxyalcohols under basic conditions,
which experienced exclusive isomerization to the corre-
sponding 1-CF3-2,3-epoxyalcohols because the alkoxide of
the latter was significantly stabilized by a strongly electron-
withdrawing CF3 group. Because of the electronic property
of a CF3 group, ring opening of these epoxyalcohols would
be facilitated in a regiospecific manner so as to afford
2-substituted 1,3-diols,16 whose verification is now in
progress in our laboratory.
a Reagents and conditions: (a) Red-Al/THF, rt, 3 h. (b) 2,2-
Dimethoxypropane, cat. p-TsOH/PhH, rt, 12 h.
Supporting Information Available: Detailed experi-
mental procedures and characterization data for all new
compounds (3-9) and computational details for E-anti-EA1,
-EA2, E-syn-EA1, and Z-anti-EA2. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
analysis of these materials demonstrated the 1,3-syn relation-
ship for the former on the basis of the coupling constants
observed, J(H2-H3a) ) 11.8 Hz, J(H3a-H4) ) 11.5 Hz,
J(H2-H3b) ) 2.8 Hz, J(H3b-H4) ) 2.6 Hz, which unam-
biguously proved the axial disposition of H2, H3a, and H.4
These values for the 1,3-anti isomer were J(H2-H3a) ) 9.5
Hz, J(H3a-H4) ) 5.9 Hz, J(H2-H3b) ) 6.6 Hz, J(H3b-H4)
) 9.7 Hz, supporting the anti and syn relationships between
H2-H3a and H3a-H4, respectively. A similar tendency was
also found for the acetonides 9b and 9c, which led to
confirmation of the diastereoselection at the reduction of E-5
OL048229X
(15) Rychnovsky, S. D.; Rogers, B.; Yang, G. J. Org. Chem. 1993, 58,
3511.
(16) It is known that the CF3-C-O bond is difficult to cleave because a
CF3 group (1) makes the neighboring bond strong and (2) prevents the
approach of incoming nucleophiles by electronically repulsive interaction.
See, for example, ref 8.
4076
Org. Lett., Vol. 6, No. 22, 2004