Iron-catalyzed 1,4-hydroboration of 1,3-dienes

Article abstract of DOI:10.1021/ja9048493

(Chemical Equation Presented) A chemo-, regio-, and stereoselective iron-catalyzed 1,4-hydroboration of dienes that affords γ-disubstituted allylboranes has been developed. 1,4-Hydroboration of 2-substituted dienes forms allylborane products with (E)-trisubstituted double bonds exclusively.

Full text of DOI:10.1021/ja9048493

Published on Web 08/24/2009
Iron-Catalyzed 1,4-Hydroboration of 1,3-Dienes
Jessica Y. Wu, Benoˆıt Moreau, and Tobias Ritter*
Department of Chemistry and Chemical Biology, HarVard UniVersity, 12 Oxford Street, Cambridge, MA 02138
Received June 13, 2009; E-mail: ritter@chemistry.harvard.edu
Iron can adopt formal oxidation states ranging from -II1 to
+VI.2 Iron complexes are used as catalysts in synthetic chemistry
for carbon-heteroatom3 and carbon-carbon bond-forming reac-
tions.4 Low-valent iron complexes can catalyze cross-coupling,4
cycloisomerization,5 and cycloaddition reactions.6,7 We are inter-
ested in iron catalysis for the identification of useful, previously
inaccessible reaction chemistry and report here C-B bond formation
by hydroboration of 1,3-dienes. To our knowledge, there are no
other examples of Fe-catalyzed hydroboration reactions of olefinic
substrates. The allylborane products are formed regio- and stereo-
selectively with (E)-double bond geometry exclusively and are
challenging to access selectively with conventional chemistry.
We have previously reported a 1,4-addition reaction of R-olefins
to dienes using an iminopyridine-ferrous chloride complex8 with
magnesium metal as an in situ reducing agent.9 In this communica-
tion, we describe the use of analogous, readily prepared iminopy-
ridine-derived iron complexes as catalysts for the regioselective
1,4-addition of pinacolborane (HBPin) to substituted 1,3-dienes (eq
1).
Evaluation of different bidentate ligands (see the Supporting
Information) showed that iminopyridine ligands gave the highest
yields for hydroboration. The redox activity of iminopyridine
ligands may play a role in effecting efficient catalysis.20 Ligand
optimization revealed that variation of the substituent of the imine
nitrogen modulates the 1,4-regioselectivity to favor either the
branched or linear isomer (eqs 1 and 2). 1,4-Addition of pina-
colborane to myrcene (1) catalyzed by 3·FeCl2 produced gera-
nylpinacolborane (2a) with 93:7 (2a/2b) regioselectivity and >99:1
E/Z selectivity in 89% overall yield (eq 1). When catalyst 4·FeCl2
was used, the regioselectivity was inverted, and branched allylbo-
rane 2b was obtained as the major product in 78% isolated yield
(92% yield of combined regioisomers; eq 2). The ligand-controlled
regioselectivity is of synthetic value and may be set during
migratory insertion (see the mechanistic hypothesis shown in
Scheme 1).
Hydroboration of various 1,3-dienes occurred within 4 min to
4 h, depending on the substrate and ligand, and proceeded equally
efficiently with commodity (98%) and high-purity (99.998%)
ferrous chloride as the iron source. As shown in Table 1,21 the
regioselectivity for 1,4-hydroboration of 2-substituted dienes in-
creased as the size of the 2-substituent increased: isoprene afforded
prenylboronate ester 10a with 90:10 regioselectivity; geranylborane
2a was obtained with 93:7 regioselectivity; and 2-cyclohexylbuta-
diene (11) and 2-dimethyl(phenyl)silylbutadiene (13) were hy-
droborated with regioselectivities of 94:6 and 99:1, respectively.
The regioselectivity of 1,4-addition to 13 could be inverted from
99:1 to <1:99 by using the iron complex 4·FeCl2, which differs
from iron complex 3·FeCl2 only in the iminopyridine substituent
(entries 6, 7). Both of the allylboranes 14a and 14b are difficult to
synthesize otherwise: silaboration of allenes yields 2-borylallylsi-
lanes.22 In addition to 2-substituted dienes, 2,3-disubstituted diene
5 participated in Fe-catalyzed hydroboration to regioselectively give
allylborane 6. The 1,4-disubstituted diene 7 was hydroborated
efficiently to give allylborane 8. Hydroboration of the 1,2-
disubstituted diene (+)-nopadiene (15) gave C-B bond formation
at the less-substituted diene terminus with 98:2 regioselectivity.23
The Fe-catalyzed hydroboration can be performed in the presence
of electrophilic functionality, such as the ester in 19, which is
incompatible with the basic conditions of traditional allylborane
syntheses.11a Notably, the hydroboration is chemoselective, and 1,4-
addition to 1,3-dienes proceeds without hydroboration of isolated
Allylboranes are versatile intermediates employed in oxidation
to form allylic alcohols,10 allylation to give homoallylic alcohols11
and amines,12 and Suzuki cross-coupling reactions.13 Traditional
methods for synthesizing allylboranes involve basic main-group
organometallics, such as Grignard and organolithium reagents, that
are incompatible with electrophilic functional groups.11a While
transition-metal-catalyzed hydroboration of olefins has been studied
extensively with great success,14 hydroboration of dienes to access
allylboranes is less-established. Pd(0) catalyzes the 1,4-addition of
catecholborane to unfunctionalized 1,3-dienes such as 1,3-penta-
diene and isoprene to give (Z)-branched allylboranes,15 while NiII-
16
and RhI-catalyzed17 reactions are selective for 1,2-addition.
The synthesis of linear (E)-γ-disubstituted allylboranes is at-
tractive because, for example, they can afford trisubstituted allylic
alcohols stereospecifically and add to electrophiles to generate
quaternary stereocenters with control of diastereoselectivity. Chal-
lenges in the synthesis of linear (E)-γ-disubstituted allylboranes
via hydroboration of 1,3-dienes include control of chemoselectivity
to favor 1,4- over 1,2-addition, control of regioselectivity to favor
C-B bond formation at a single diene terminus, and control of
stereoselectivity to favor (E)-olefin geometry. The hydroboration
reaction presented herein controls all three types of selectivity. A
general method for synthesizing linear (E)-γ-disubstituted allylbo-
ranes has not been reported previously.18
We observed that hydroboration of myrcene (1) catalyzed by
the iminopyridine-iron(II) complex 3·FeCl2 upon addition of
magnesium metal afforded geranylpinacolborane (2a) in 80% yield
after 3 h at 23 °C (eq 1). The combination of ligand, ferrous
chloride, and magnesium was necessary for catalysis. Pinacolborane
generally afforded allylboranes that were stable toward air, water,
and chromatography on silica gel; other borolanes, such as those
derived from catecholborane, were not stable toward hydrolysis or
chromatography on silica gel.19
9
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J. AM. CHEM. SOC. 2009, 131, 12915–12917 12915

C O M M U N I C A T I O N S
Table 1. Substrate Scope for Fe-Catalyzed 1,4-Hydroboration of 1,3-Dienes
a Using 5 mol % 4·FeCl2. b Using 15 mol % 2,3-dimethyl-1,3-butadiene as an additive.21 c Using 1.5 equiv of HBPin. d Product degradation was
observed upon purification by chromatography on silica gel; the yield can be higher if used in situ. See, for example, eq 3.
olefins such as in 21. We attribute the high chemoselectivity of
diene versus olefin hydroboration to the affinity of 1,3-dienes for
low-valent iron.24 The Fe-catalyzed hydroboration of every diene
investigated was selective for 1,4-addition to produce the allylborane
stereo- and regioselectively. 1,2-Addition products could not be
(15) followed by oxidation to provide only the (E)-isomer 23 in
84% yield over two steps.
1
detected by H NMR analysis. The major regioisomers 12a-22a
were formed with (E)-double bond geometry exclusively, consistent
with the mechanism proposed in Scheme 1. Products with trisub-
stituted double bonds can otherwise be challenging to synthesize
stereoselectively, especially when the substituents have similar
sizes.25
The Fe-catalyzed reaction can also be used in a one-pot
hydroboration-allylation reaction, as shown in eq 5. Addition of
benzaldehyde subsequent to 1,4-hydroboration of ester 19 gave a
93:7 mixture of homoallylic alcohols 25a and 25b resulting from
the two regioisomers 20a and 20b. Homoallylic alcohol 25a was
formed as a single diastereomer, as determined by 1H NMR
spectroscopy. Lactone formation afforded 26 in 85% yield as a
single diastereomer. Alcohol 25a and δ-lactone 26 both contain an
all-carbon quaternary center; the relative stereochemistry in 25a
and 26 is a result of the E configuration of the γ-disubstituted
allylborane generated in the Fe-catalyzed hydroboration.
Allylic alcohols with trisubstituted double bonds are substrates
for asymmetric catalytic reactions, such as Noyori hydrogenation,26
isomerization to generate chiral aldehydes,27 and Sharpless asym-
metric epoxidation.28 All of these reactions require the alcohol
substrate to be stereochemically pure with respect to double bond
geometry in order to attain high levels of enantioselectivity. The
Fe-catalyzed hydroboration presented here provides ready access
to allylic alcohols with (E)-trisubstituted double bonds in high
stereoselectivity (>99:1; eqs 3 and 4).25 For example, allylic alcohol
23 was synthesized in two steps by hydroboration of (+)-nopadiene
9
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C O M M U N I C A T I O N S
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Acknowledgment. We thank Novartis for a fellowship for
J.Y.W., Materia for a generous donation of Grubbs II catalyst, and
the ACS PRF.
Supporting Information Available: Detailed experimental proce-
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