A two-component catalyst system for asymmetric allylic alkylations with alcohol pronucleophiles [19]

Full text of DOI:10.1021/ja983238k

12702
J. Am. Chem. Soc. 1998, 120, 12702-12703
palladium catalyst may control the last issue,8 resolution of the
first three prerequisites required the discovery of a catalyst for
the alcohol nucleophile to provide the chemo- and regioselectivity.
In our search for achieving this goal, we have uncovered a
remarkable catalytic role for trialkylboranes in promoting the
nucleophilic addition of alcohols chemo-, regio-, and enantiose-
lectively to vinyl epoxides.
As suspected, the reaction of vinyl epoxide 2a with methanol
or benzyl alcohol in the presence of Pd(0) and the chiral ligand
3a led to no reaction or almost no reaction (<6%), respectively,
over 18 h.
A Two-Component Catalyst System for Asymmetric
Allylic Alkylations with Alcohol Pronucleophiles
Barry M. Trost,* Ernest J. McEachern, and F. Dean Toste
Department of Chemistry
Stanford UniVersity
Stanford, California 94305-5080
ReceiVed September 11, 1998
The importance of chiral nonracemic building blocks for the
synthesis of biologically important target molecules continues to
grow, especially as a result of the explosion of molecular targets
in the pharmaceutical and agrichemical arenas. Tartaric acid
exemplifies the value of chiral nonracemic oxygen-bearing
synthetic intermediates1 but also some of the problems, dif-
ferentiating and manipulating the functionality. An alternative
family, wherein such functional group manipulations are simpler,
is the vinylglycidols 1, but their access in chiral, nonracemic form
is frequently not straightforward.2-5 The ready access to racemic
vinyl epoxides via epoxidation of 1,3-dienes6 makes their dera-
cemization, in contrast to a kinetic resolution, to form chiral
nonracemic vinylglycidols very attractive, especially if the two
hydroxyl groups are differentiated intrinsic to the deracemization
reaction. Palladium-catalyzed asymmetric additions of alcohols
could be a solution if (i) the normal poor reactivity of alcohols
as nucleophiles7 could be overcome, (ii) the alcohols would react
regioselectively to give the vicinal hydroxyether, (iii) the product
primary alcohol would not compete effectively with the reactant
alcohol (a most subtle type of chemoselectivity), and (iv)
diastereomeric interconversion of the π-allylpalladium intermedi-
ates could occur faster than nucleophilic attack. Whereas the
As envisioned in eq 1, treatment of isoprene or where mono-
(1) For applications towards vinylglycidol, see: Rao, A. V.; Reddy, E. R.;
Joshi, B. V.; Yadav, J. S. Tetrahedron Lett. 1987, 28, 6497; Howes, D. A.;
Brookes, M. H.; Coates, D.; Golding, B. T.; Hudson, A. T. J. Chem. Res. (M)
1983, 217. For an overview, see: Seebach, D.; Hungerbu¨hler, E. In Modern
Synthetic Methods 1980; Scheffold, R.; Ed.; Otto Salle Verlag: Frankfurt am
Main, 1980; Vol. 2, pp 91-171.
epoxide with 1 equiv of trimethyl borate in the presence of
(dba)3Pd2‚CHCl3 (4) and ligand 3a gave the desired glycol
monoether 1a in 80% yield but only 2% ee. Independent
experiments show that trialkylborates do not react with the epoxide
in the absence of a palladium catalyst. Since equilibration of
the π-allylpalladium intermediates (as depicted in eq 1) must be
fast compared to alkoxide transfer to obtain good ee, we decreased
the concentration of the transfer agent, trimethylborate, to 1%
but added a stoichiometric amount of methanol. Indeed, the ee
increased to 49%. Decreasing the effectiveness of the boron to
form an “ate” complex by switching to diethylmethoxyborane9,10
increased the ee in both the stoichiometric and catalytic reactions
to 58% and 90%, respectively. Generating diethylmethoxyborane
in situ from triethylborane and methanol led to the most
convenient and best results, giving an 88% isolated yield and 94%
ee of 5a (R ) R′ ) CH3).
(2) A kinetic resolution of butadiene monoepoxide to form vinylglycidol
has been reported, see: Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen,
E. N. Science 1997, 277, 936.
(3) For enzymatic resolution of derivatives of vinylglycidol, see: Boaz,
N. W.; Zimmerman, R. L. Tetrahedron: Asymmetry 1994, 5, 153; Suzuki, T.;
Kasai, N.; Minamiura, N. Tetrahedron: Asymmetry 1994, 5, 239. For solvolysis
of the corresponding enantiomerically pure vinyl epoxide to form the
monoethers of vinylglycidol in addition to varying amounts of 1,4-adduct,
see: Boaz, N. W. Tetrahedron: Asymmetry 1995, 6, 15. For kinetic resolution
of the monotosylate by asymmetric epoxidation, see: Neagu, C.; Hase, T.
Tetrahedron Lett. 1993, 34, 1629.
(4) For other asymmetric syntheses of vinylglycidol and the 2-methyl
derivative, see: Saibata, R.; Sarma, M. S. P.; Abushnab, E. Synth. Commun.
1989, 19, 3077; Jurczak, J.; Pikul, S.; Bauer, T. Tetrahedron 1986, 42, 447;
Ohwa, M.; Kogure, T.; Eliel, E. L. J. Org. Chem. 1986, 51, 2599.
(5) Asymmetric dihydroxylation of butadiene or isoprene has not been
reported to our knowledge. trans-Piperylene is reported to give moderate yields
and moderate chemoselectivity with ee’s of 90% and 72% for the two diols.
See Becker, H.; Soler, M. A.; Sharpless, K. B. Tetrahedron 1995, 51, 1345;
For a review, see Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B.
Chem. ReV. 1994, 94, 2483.
Using these conditions, a variety of alcohols were added to
isoprene monoepoxide as summarized in Table 1. The examples
show good chemoselectivity wherein nitriles, esters, and ketones
all are tolerated. With 2-cyanoethanol (Table 1, entry 4), the ee
was 81% under our standard conditions. Assessing that the source
of the somewhat diminished ee might still arise from too rapid
trapping of the π-allylpalladium intermediate, we switched to a
more hindered borane, tri-sec-butylborane, as the cocatalyst.
(6) Both butadiene and isoprene monoepoxides are commercially available.
Such epoxides are available by the direct epoxidation of the corresponding
dienes. For butadiene monoepoxide from diene and oxygen, see: Monnier, J.
R. In 3rd World Congress on Oxidation Catalysis, 1997; Grasselli, R. K.,
Oyama, S. T., Gaffney, A. M., Lyons, J. E., Eds.; Elsevier: New York, 1997;
pp 135-149. For isoprene monoepoxide, see: Eletti-Bianchi, G.; Centini, F.;
Re, L. J. Org. Chem. 1976, 41, 1648; Fransen, M. R.; Palings, I.; Lugtenberg,
J. Recl. TraV. Chim. Pays-Bas 1980, 99, 384.
(7) Cf. Trost, B. M.; Tenaglia, A. Tetrahedron Lett. 1988, 29, 2931; Sinou,
D.; Frappa, I.; Lhoste, P.; Powanski, S.; Kryczka, B. Tetrahedron Lett. 1995,
36, 1251; For some recent intramolecular processes, see: Fournier-Nguefack,
C.; Lhoste, P.; Sinou, P. Tetrahedron 1997, 53, 4353; Thorey, C.; Wilken, J.;
He´nin, F.; Martens, J.; Mehler, T.; Muzart, J. Tetrahedron Lett. 1995, 36,
5527. For a review, see: Godleski, S. A. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford,
1991; Vol. 4, pp 585-662.
(8) Trost, B. M.; Bunt, R. C. Angew. Chem., Int. Ed. Engl. 1996, 35, 99.
(9) For alkenylborane coupling, see: Miyaura, N.; Tanabe, Y.; Suginome,
H.; Suzuki, A. J. Organomet. Chem. 1982, 233, C13.
(10) Commonly, such reagents transfer alkyl groups, see: Abe, S.; Miyaura,
N.; Suzuki, A. Bull. Chem. Soc. Jpn. 1992, 65, 2863.
10.1021/ja983238k CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/20/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 48, 1998 12703
Table 1. Boron Co-Catalyzed Asymmetric Addition of Alcohols
our standard conditions with ligand 3a and methanol as a
nucleophile, a 78% yield of adduct of only 25% ee was obtained.
In addition, a significant amount of oligomer, wherein the initial
product served as nucleophile, was also produced. Replacing the
benzo-linked ligand 3a with the naphtho-linked ligand 3b8
decreased the amount of the oligomer and enhanced the ee. Table
2 summarizes the results. In most cases, the use of tri-sec-
butylborane was advantageous over that of triethylborane.
The effect of boranes on the ability of alcohols to serve as
nucleophiles in their asymmetric addition to vinyl epoxides in a
dynamic kinetic resolution is dramatic and decisive. Thus, this
two-component catalytic system has the palladium activating the
electrophile and boron, the nucleophile. Although the current
observations question the role, if any, of the boron in the epoxide
opening as in eq 1, a fuller discussion of the mechanism is
postponed until more detailed studies are completed.
to Isoprene Monoepoxidea
This new chemo-, regio-, and enantioselective opening of
racemic vinyl epoxides in a dynamic kinetic resolution (a
deracemization) is a valuable and flexible entry to these versatile
building blocks. These materials constitute differentiated diols
wherein the more substituted alcohol is selectively “protected,”
a type of differentiation not readily accessible by selective
monoprotection of the diol. As an example, the PMB derivative
can readily be converted to the benzylidene analogue 9,11 wherein
both alcohols are protected, and the latter hydrolyzed to the
glycidol analogue 1012 (eq 2). A 1,4-dioxanone 7 (Table 1, entry
a All reactions performed using a 1:1 ratio of alcohol to 2a with 1
mol % 4, 3 mol % ligand 3a, 1 mol % R3B in methylene chloride at
room temperature unless stated otherwise. b Yields are for isolated pure
product. c Determined by chiral GC with J&W Cyclosil B column or
HPLC with Chiralcel OD or Chiralpak AS columns. d Analysis
performed on corresponding benzoate. e Reaction performed at 40 °C.
f Corresponds to enantioselectivity at tertiary center, secondary alcohol
is a 1:1 epimeric mixture. g Also required 5 mol % DMAP. h Deter-
mined after dehydration to 1,4-dioxene.
Table 2. Boron Co-Catalyzed Asymmetric Addition of Alcohols
6) and a 1,4-dioxene 11 (Table 1, entry 7 and eq 3) are also
accessed asymmetrically. A Claisen rearrangement13 of the latter
provided a pyrane 12 asymmetrically (eq 3).
to Butadiene Monoepoxidea
The concept of this two-component catalyst system to activate
both the nucleophile and electrophile may expand the metal-
catalyzed allylic alkylation to additional nucleophiles beyond
alcohols, thereby considerably expanding the scope of this
important transformation. Interestingly, and in stark contrast to
Suzuki-type couplings, alkoxy transfer dominates over alkyl or
hydride transfer with the dialkylalkoxyboranes and the electro-
philes used herein.
a See footnote a, Table 2, except that 3 mol % of ligand 3b was
employed. b Yields in brackets are based upon NMR and GC analyses;
otherwise yields are for isolated pure product. c Reaction performed
with a 2:1 ratio of alcohol to epoxide at 40 °C in the presence of 5%
DMAP. d Reaction performed at 40 °C. e Performed with a 1.1:1 ratio
of alcohol to epoxide at 40 °C in the presence of 5% DMAP.
Acknowledgment. We thank the National Science Foundation and
the National Institutes of Health, Institute of General Medical Sciences,
for the generous support of our programs. E.J.M is a NSERC postdoctoral
fellow. We thank Dr. J. N. Cumming for his help in optimizing two of
the reactions reported herein.
Indeed, the ee increased to 90%. A similar effect was observed
with methyl glycolate as the nucleophile (Table 1, entry 6).
Secondary alcohols do not participate, a fact that is dramatically
illustrated by entry 5 (Table 1). It should be noted that no
regioisomeric 1,4- products were detected in any case.
Supporting Information Available: General experimental procedure
and characterization data for 5a-5j, 7-9, 11, 12, and benzoate ester of
5c and Table, Effect of Boron Source in Additions of Methanol to Isoprene
Monoepoxide (9 pages, print/PDF). See any current masthead page for
ordering information and Web access instructions.
Extension to butadiene monoepoxide must take cognizance of
the higher susceptibility of the secondary center toward nucleo-
philic addition. In this regard, the fact that the carbon undergoing
attack in the isoprene epoxide case is tertiary, which slows down
reaction, becomes beneficial with respect to ee. Indeed, under
JA983238K
(11) Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett. 1982, 32,
889.
(12) Ohwa, M.; Kogure, T.; Eliel, E. L. J. Org. Chem. 1986, 51, 2599.
(13) Paquette, L. A.; Sweeney, T. J. Tetrahedron 1990, 46, 4487.