Catalytic EnantioselectiVe Allylboration of Aldehydes
aldehydes, whereas others require expensive transition-metal
catalysts or employ highly toxic trialkylallylic tin reagents or
chromium-based catalysts. Several very effective and popular
aldehyde allylation methods based on boron reagents have been
developed, but they all require a stoichiometric chiral inductor.9
Our laboratory has advocated the development of a catalytic
enantioselective allylboration as an attractive alternative.10
Indeed, pinacol allylboronates are air- and water-stable, non-
toxic, and readily formed reagents whose additions to aldehydes
are characterized by very high levels of chemo-, regio-, and
diastereoselectivity. Moreover, a plethora of efficient methods
are available for the preparation of functionalized allylic
boronates.11,12 Recently, we discovered that both Lewis acids13
and Brønsted acids14 can catalyze additions of allylboronates
to aldehydes. These mechanistically novel allylboration proce-
dures15 have matured into an efficient enantioselective Brønsted
acid-catalyzed allylation and crotylation of aliphatic aldehydes,
producing homoallylic alcohol products in up to 95% ee (Figure
1).16 This system, based on Yamamoto’s elegant concept of
“Lewis acid assisted Brønsted acidity” with chiral diol-SnCl4
complexes,17 provides useful selectivities, but the scope of useful
substrates remains quite limited with the optimal diol Vivol (4a)
(Figure 1). Here, we report the design and applications of an
improved catalyst that provides significantly higher ee’s with
useful aliphatic aldehydes and a wider range of allylic boronates
including the unprecedented 2-bromoallylboron pinacolate. As
demonstrated in a total enantioselective synthesis of (+)-
dodoneine, the resulting catalytic enantioselective allylation
FIGURE 1. Vivol·SnCl4-catalyzed allylboration of aldehydes.
methodology can match or surpass the efficiency of the popular
Brown9b and Keck6b allylation reactions.
Results
Design and Evaluation of an Improved Chiral Diol ·SnCl4
Catalyst. While developing an optimal chiral diol for the
diol·SnCl4 catalysis of the prototype allylation reaction between
hydrocinnamaldehyde (2a) and allylboron pinacolate (1a), we
realized that the slow background uncatalyzed allylation com-
peted non-negligibly with the catalytic process. In the course
of 4-5 h, approximately 3-4% of racemic 3a was formed,
consequently eroding the enantioselectivity by a few percent
of ee.16c
(6) (a) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-
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We rationalized that a more acidic diol and thus more active
Brønsted acid was required in order to shorten the reaction times
and suppress the background uncatalyzed reaction. In this regard,
it was expected that electron-withdrawing substituents on the
diol’s aryl units could decrease the pKa of the hydroxylic protons
in the diol ·SnCl4 complex. It was also deemed preferable to
place the substituent in the para position as opposed to the ortho
or meta positions because the X-ray crystallographic structure
of the vivol ·SnCl4 complex shows an intimate steric relationship
between the cyclooctyl unit and the aryl group of adjacent
carbons, which appear to stack with one another.16c Upon
inspection of the crystal structure, modulating electronic effects
at the para position of the aryl groups appeared to least disrupt
the catalyst’s spatial arrangement. To this end, diols 4b and 4c
with respective p-fluoro and trifluoromethyl substituents were
targeted (Figure 2). In order to support the hypothesis of
electronic modulation of catalyst acidity, diol 4d with electron-
donating methoxy substituents was also planned. Diols 4b and
4c were prepared using a previously published sequence,16c
whereas diol 4d required an alternative route (see the Supporting
Information). The synthesis of the optimal diol, 4b, is outlined
in Scheme 1 and features an efficient sequence of six high-
yielding steps similar to that reported for the nonfluorinated
analogue 4a. Starting from commercially available 2-bromo-
4-fluorobenzaldehyde, a stereoselective McMurry coupling
yielded the corresponding trans-stilbene 5 in 76% yield.18
Sharpless asymmetric dihydroxylation under the influence of
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(11) Kennedy, J. W. J.; Hall, D. G. In Boronic Acids; Hall, D. G., Ed.; Wiley-
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(12) Lachance, H.; Hall, D. G. Allylboration of Carbonyl Compounds. Org.
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