Regio- and stereocontrol in rhenium-catalyzed transposition of allylic alcohols

Article abstract of DOI:10.1021/ja101673v

A hydroxyl group-directed, highly regio- and stereoselective transposition of allylic alcohols based on rhenium catalysis has been developed. The method is suitable for a direct isomerization of acetals into the thermodynamically preferred isomer as long as one of the hydroxyl groups is allylic. This method will expand the scope of rhenium-catalyzed alcohol transpositions for complex molecule synthesis.

Full text of DOI:10.1021/ja101673v

Published on Web 04/13/2010
Regio- and Stereocontrol in Rhenium-Catalyzed Transposition of Allylic
Alcohols
Aaron T. Herrmann, Tatsuo Saito, Craig E. Stivala, Janine Tom, and Armen Zakarian*
Department of Chemistry and Biochemistry, UniVersity of California, Santa Barbara, California 93106-9510
Received March 3, 2010; E-mail: zakarian@chem.ucsb.edu
Scheme 1. Re-Catalyzed Transposition of 1
Direct catalytic transposition of allylic alcohols is a powerful
approach to the synthesis of complex hydroxylated organic com-
pounds.1 Several transition metal catalysts have been developed
for this purpose, including vanadium,2 molybdenum,2 and rhenium
reagents.3 Among these, rhenium(VII) oxide and triphenylsilyl
perrhenate have been found to be superior in terms of reactivity
and chemoselectivity, displaying high activity at low temperatures
with no competitive oxidation observed with some of the other
catalysts. One drawback of the reversible process (eq 1) is a general
lack of regioselectivity;4 stereoselectivity in the transposition of
primary allylic alcohols is also low.
Table 1. Influence of the Catalyst and Reaction Time
In this communication, we describe a practical method that allows
for control of the regio- and stereoselectivity in the rhenium-
catalyzed transposition of allylic alcohols, expanding the scope of
the reaction for the stereoselective synthesis of complex molecules.5
In our initial experiments, rearrangement of substrate 1 in the
presence of Re2O7 (2.5 mol %) occurred with low regio- and
stereoselectivity as expected, delivering 2 with 60% conversion as
a 3:2 mixture of diastereomers (Scheme 1). We hypothesized that
the reaction medium must be slightly acidic due to formation of a
catalytic amount of perrhenic acid (pKa ) 1.25)6 upon interaction
of rhenium(VII) oxide with the substrate and/or adventitious water.7
In the presence of a catalytic acid the rearranged product can in
principle be trapped as an acetal or ketal, and then the 1,3-syn
diastereomer should be favored on thermodynamic grounds.
Remarkably, upon exposure of 1 to benzaldehyde dimethyl acetal
and Re2O7 (2.5 mol %), essentially a single product was formed in
94% yield after 20 h at room temperature. Thus, the rhenium
catalyst performs a dual catalytic function as a transition metal
catalyst for the hydroxyl group transposition and as an acid catalyst
for acetal formation.
a Measured by 500 MHz NMR spectroscopy using a crude mixture of
products.
Scheme 2. Formation of the Acetonide and PMP-Acetals
Screening of the reaction parameters demonstrated that although
a number of solvents can be used (toluene, Et2O, THF, CH2Cl2),8
dichloromethane provides the best results in terms of reaction rate.
Typically, reactions are characterized by a rapid formation of a
diastereomeric mixture of rearranged diol acetals (within ∼20 min
at room temperature) followed by slow equilibration of the acetals
to the 1,3-syn product (3).
The influence of reaction time with alternative rhenium catalysts
is summarized in Table 1. With all three catalysts studied,
methyltrioxorhenium (MTO), Ph3SiOReO3, and Re2O7, the rear-
rangement/acetalization was complete within 3 h at room temper-
ature. As expected, MTO is the least reactive catalyst.2c,9 Notably,
with all of the three rhenium catalysts the initial acetal formation
was followed by equilibration to 3. The highest rate of equilibration
was observed with Re2O7, generating 3 with >98% selectivity after
20 h. With Ph3SiOReO3, a high level of selectivity (96:4) was also
reached after 20 h at room temperature.
As illustrated in Scheme 2, the highly stereo- and regioselective
transposition can be achieved with other commonly employed diol
masking groups. Acetonide formation occurred in an 81% yield
(96% ds), and the p-methoxyphenyl (PMP) acetal 6 was isolated
in a 95% yield with greater than 98% diastereoselectivity.
The reaction scope with a range of substrates of higher
complexity was explored next (Table 2). Migration of the resident
benzylidene group accompanying the transposition was possible
as illustrated in entry 1 (Table 2). Desilylation can be accomplished
simultaneously without a need for an additional step (entry 2). A
Cbz-protected primary amine is compatible with the reaction
conditions, and the relative stereochemistry of the amino alcohol
has no influence on the stereoselectivity of the reaction (entries 3,
9
5962 J. AM. CHEM. SOC. 2010, 132, 5962–5963
10.1021/ja101673v  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3. Reactivity in the Absence of a Brønsted Acid
Table 2. Scope of the Re-Catalyzed Transposition/Acetalization
with Complex Substratesa
suppressed the transposition and acetalization with either Re2O7 or
Ph3SiOReO3. Addition of Bu4NOAc or a proton sponge also
suppressed the reaction. These results may be explained either by
increasing the pH of the medium or by a modification of the catalyst
through irreversible complexation.4b,7 To conclusively establish
reactivity in the absence of acid or alternative ligands, we prepared
the catalyst in situ using an excess of strongly basic Me3SiOK (0.35
equiv) and Re2O7 (0.20 equiv) in THF.10 As shown in Scheme 3,
the system maintained full catalytic activity, indicating a possibility
where the acetal formation is likely due to the Lewis acidic character
of trimethylsilyl perrhenate.
In summary, we developed a method that allows the control of
regio- and stereoselectivity by a neighboring hydroxyl group in the
Re-catalyzed transposition of allylic alcohols with accompanying
formation of acetals. Further studies aimed at a better understanding
of the process are underway.
Acknowledgment. This work was supported by the NIH/
NIGMS (R01 GM077379). Additional support was kindly provided
by the Eli Lilly (Lilly Grantee Award to A.Z.), Amgen (YIA to
A.Z.), the Tobacco-Related Disease Research Program (Predoctoral
Award to C.E.S.), and the Japan Society for the Promotion of
Science (JSPS, postdoctoral fellowship to T.S.). J.T. is an under-
graduate DeWolfe Fellow.
Supporting Information Available: Experimental procedures,
1
copies of H and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
a Reactions were performed in CH2Cl2 (∼0.2 M) with 2.5 mol % of
Re2O7 and 2.0 equiv of PhCH(OMe)2 or 4-MeOPhCH(OMe)2; dr is
determined by 500 MHz 1H NMR.b Overall yield after treatment with
TBAF.c RdH/RdTBS 5.3:1.
(1) Review: Bellemin-Laponnaz, S.; Le Ny, J. P. C. R. Chimie 2002, 5, 217–
224.
(2) Mo, V: (a) Chabardes, P.; Kuntz, E.; Varagnat, J. Tetrahedron 1977, 33,
1775–1783. (b) Akai, S.; Tanimoto, K.; Kanao, Y.; Egi, M.; Yamamoto,
T.; Kita, Y. Angew. Chem., Int. Ed. 2006, 45, 2592–2595. (c) Hosogai, T.;
Fujita, Y.; Ninagawa, Y.; Nishida, T. Chem. Lett. 1982, 357–360. (d)
Matsubara, S.; Okazoe, T.; Oshima, K.; Takai, K.; Nozaki, H. Bull. Chem.
Soc. Jpn. 1985, 58, 844–849. (e) Belgacem, J.; Kress, J.; Osborn, J. A.
J. Am. Chem. Soc. 1992, 114, 1501–1502. (f) Belgacem, J.; Kress, J.;
Osborn, J. A. J. Mol. Catal. 1994, 86, 267–285.
4). Upon prolonged exposure (20 h), a complete removal of acid
sensitive PMB and TBDPS groups was observed, which were
replaced with the benzylidene acetal (entries 5, 6). A more oxidized
p-methoxybenzoyl (MBz) group and shorter reaction times (4 h)
resulted in a much improved conservation of the original protecting
groups (entries 7, 8). Functionalized tetrahydropyran substrates
underwent the transposition reaction with the generally observed
high regiocontrol and high stereoselectivity (entries 9, 10). Ther-
modynamically disfavored 1,1-disubstituted alkenes can be readily
prepared in high yield (entry 11).
(3) Re(VII): (a) Bellemin-Laponnaz, S.; Gisie, H.; Le Ny, J. P.; Osborn, J. A.
Angew. Chem., Int. Ed. Engl. 1997, 36, 976–978. (b) Bellemin-Laponnaz,
S.; Le Ny, J. P.; Osborn, J. A. Tetrahedron Lett. 2000, 41, 1549–1552.
MTO: (c) Jacob, J.; Espenson, J. H.; Jensen, J. H.; Gordon, M. S.
Organometallics 1998, 17, 1835–1840.
(4) The following reports describe solutions to this problem with certain types
of substrate:(a) Morrill, C.; Grubbs, R. H. J. Am. Chem. Soc. 2005, 127,
2842–2843. (b) Morrill, C.; Beutner, G. L.; Grubbs, R. H. J. Org. Chem.
2006, 71, 7813–7825. (c) Hansen, E. C.; Lee, D. J. Am. Chem. Soc. 2006,
128, 8142–8143.
An intriguing aspect of the reaction is that the transposition and
acetalization are typically complete in an initially nonstereoselective
manner within minutes (less than 30 min), followed by relatively
slow isomerization to the preferred stereoisomer. In a control
experiment, when a 6:3:1 diastereomeric mixture of benzylidene
acetals 4 was subjected to the standard reaction conditions (dry
CH2Cl2, argon atmosphere, 2.5 mol % Re2O7, rt, 20 h), a single
stereoisomer (3) was isolated in 90% yield. In contrast, treatment
of the same mixture with p-TsOH (5 mol %, dry CH2Cl2, argon
atmosphere, rt, 21 h) resulted in no change.
(5) For a review of other methods for stereoselective 1,3-diol synthesis, see:
Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307–1370.
(6) (a) Bailey, N.; Carrington, A.; Lott, K. A. K.; Symons, M. C. R. J. Chem.
Soc. 1960, 290–297 Perrhenic acid is known to exist as dirhenium dihydra-
toheptoxide Re2O7(OH2)2 in low-water media such as concentrated aqueous
solutions. The HReO4 form exists in dilute aqueous solutions: (b) Beyer, H.;
Glemser, O.; Krebs, B. Angew. Chem., Int. Ed. 1968, 7, 295–296.
(7) (a) Tadpetch, K.; Rychnovsky, S. D. Org. Lett. 2008, 10, 4839–4842. (b)
Gesinski, M. R.; Tadpetch, K.; Rychnovsky, S. D. Org. Lett. 2009, 11,
5342–5345.
(8) Useful levels of diastereoselectivity (90% or more) were obtained in toluene
and THF. See Supporting Information for details.
(9) Hutchinson, J. M.; Lindsay, H. A.; Dormi, S. S.; Jones, G. D.; Vicic, D. A.;
McIntosh, M. C. Org. Lett. 2006, 8, 3663–3665.
(10) Edwards, P.; Wilkinson, G. J. Chem. Soc., Dalton Trans. 1984, 2695–2712.
As was also noted by Grubbs and Rychnovsky,4b,7 addition of
0.2 equiv of 2,6-di-tert-butyl-4-methylpyridine (DTMP) completely
JA101673V
9
J. AM. CHEM. SOC. VOL. 132, NO. 17, 2010 5963