Angewandte
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construction of multiple contiguous quaternary stereocen-
ters.[9] However, the formation of tertiary organoboronates by
metal-catalyzed or stoichiometric hydroboration is rare, since
hydroboration generally proceeds in an anti-Markovnikov
fashion to deliver boron to the less substituted site on the
alkene.[1,10]
Several complementary methods for the preparation of
chiral tertiary boronic esters have recently been reported
(Scheme 2). Three of these methods use bis(pinacolato)di-
boron (B2pin2) for the net hydroboration of functionalized
alkenes. For example, Tang and co-workers recently described
Scheme 3. CAHB of methylidene substrates 5 to form chiral tertiary
boronic esters 7. Typical reaction conditions: 1) [Rh(nbd)2]BF4
(2.0 mol%), (R,R)-L (4.1 mol%), pinBH (2.0 equiv), THF (c=0.04m),
408C, 3–24 h; 2) H2O2, aqueous NaOH. [a] The boronic ester was
formed in 84% yield. [b] The boronic ester was formed in 69% yield.
[c] (R)-6h was formed in 70% yield according to the NMR spectrum of
the crude product. Bn=benzyl.
Scheme 2. Recently reported approaches to the synthesis of chiral
tertiary boronic esters.
a remarkable rhodium-catalyzed reaction of a-aryl enamides
with B2(pin)2 to provide the first enantioselective synthesis of
chiral tertiary a-aminoboronic esters.[11] Shibasaki and co-
workers,[12] Hoveyda and co-workers,[13] and Feng and Yun[14]
independently developed asymmetric conjugate addition
reactions of B2(pin)2 to unsaturated esters, ketones, and
thioesters. Hoveyda and co-workers also developed an
efficient copper-catalyzed SN2’ substitution of allylic carbo-
nates by B2(pin)2.[15] Aggarwal and co-workers have very
elegantly exploited enantioselective lithiation followed by the
addition of a boronic ester and subsequent rearrangement to
prepare chiral tertiary boronic esters bearing benzyl, allyl,
propargyl, and most recently all-alkyl substituents.[16] Tertiary
boronic esters can also be constructed by deborylative
alkylation of geminal bis(boronates), as reported by Wom-
mack and Kingsbury[17] and Morken and co-workers.[18]
A series of methylidene derivatives 5 in which the vinyl
substituent R1 varies were subjected to CAHB (Scheme 3).
Oxime ether 5b (R1 = CH2Ph) was converted into the
intermediate chiral boronic ester 7b (R1 = CH2Ph), and the
tertiary alcohol 6b (70%, 94:6 e.r.) was obtained after
oxidation; alkene reduction, in this case leading to the
formation of 8 (21%, 56:44 e.r.), was the major competing
side reaction for all substrates. The isobutyl derivative 5c
(R1 = CH2CH(CH3)2) reacted similarly to give the tertiary
derivative 6c (70%, 95:5 e.r.). Several substrates with
a second site of unsaturation in the R1 substituent were also
found to undergo CAHB. Notably, only the alkene closest to
the oxime directing group underwent borylation in these
diene substrates. For example, the reaction of 1,4-dienes 5d–f
afforded monounsaturated alcohols 6d–f after oxidation.
Simple pendant oxygen and nitrogen substituents are toler-
ated, as illustrated by the formation of 6g and 6h. The level of
regioselectivity in favor of b- over g-borylation is high, except
for substrates in which the vinyl substituent R1 is more
sterically demanding. For example, 5i (R1 = cyclohexyl)
underwent predominantly g-borylation to afford the regio-
isomeric primary alcohol 9 (54%, 85:15 e.r.) after oxidation.
Trisubstituted alkene substrates typically react sluggishly
in catalyzed hydroboration but nevertheless readily under-
went oxime-directed CAHB. The borane added to the same
p-face as in the corresponding methylidene substrates and
therefore yielded the enantiomeric tertiary boronic ester
intermediate and the enantiomeric tertiary alcohol after
oxidation. For example, CAHB/oxidation of methylidene 5j
afforded predominantly (R)-6j (60%, 93:7 e.r.); the isomeric
trisubstituted substrate 10j was transformed predominantly
into (S)-6j (81%, 95:5 e.r.; Scheme 4).
Scheme 5 summarizes the results obtained for the oxime-
directed CAHB/oxidation of a number of trisubstituted
alkene derivatives 10. Not only was the opposite enantiomer
formed, but the yields observed with unhindered trisubsti-
tuted alkene substrates were often somewhat higher than
those observed for the corresponding methylidene substrates
owing to less competing alkene reduction. For example, (S)-
6a (95:5 e.r.) was formed in 84% yield from trisubstituted
alkene 10a (R1 = Me, R2 = PhCH2CH2), whereas (R)-6a (95:5
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Angew. Chem. Int. Ed. 2016, 55, 1465 –1469