Regioselective homologation of bis(boronate) intermediates derived from rhodium-catalyzed diboration of simple alkenes

Article abstract of DOI:10.1055/s-2005-869873

Regioselective homologation of alkyl-1,2-bis(catecholboronates) may be accomplished by treatment of these reactive intermediates with TMSCHN ₂. A convenient process is reported where alkene diboration and the subsequent homologation reaction are accomplished in the same reaction flask. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869873

LETTER
1749
Regioselective Homologation of Bis(boronate) Intermediates Derived from
Rhodium-Catalyzed Diboration of Simple Alkenes
Single-Pot
D
omino
i
Dibor
a
a
tion–Hom
n
ologation e M. Kalendra, Rebecca A. Dueñes, James P. Morken*
Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA
Fax +1(919)9628229; E-mail: morken@unc.edu
Received 30 March 2005
Rh(I)–QUINAP
Abstract: Regioselective homologation of alkyl-1,2-bis(catechol-
B(cat)
(cat)B
R1
B(cat)
TMS
B2(cat)2
TMSCHN2
boronates) may be accomplished by treatment of these reactive in-
termediates with TMSCHN2. A convenient process is reported
where alkene diboration and the subsequent homologation reaction
are accomplished in the same reaction flask.
R1
B(cat)
R1
R2
R2
R2
Scheme 1
Key words: boron, asymmetric catalysis, silicon, regioselectivity,
alkenes
with 1-alkene substrates. Accordingly, a Rh–QUINAP-
catalyzed diboration of 1-octene with bis(catecholatodi-
boron) was executed in THF. Subsequent to the dibora-
tion, the reaction mixture was treated with reagents for
homologation as reported by Mioskowski (3 equiv of
TMSCHN2, refluxing THF). These experiments resulted
in low product yields even with extended reaction times.
It was noted that a significant amount of non-homologated
material remained at the end of the reaction and therefore
more forcing conditions were examined. Since the Rh–
QUINAP-catalyzed diboration reaction also proceeds
well in toluene, we examined the domino reaction se-
quence in this solvent with the homologation being con-
ducted at higher temperature (Scheme 2). In this
experiment, four equivalents of trimethylsilyldiazo-
methane were added to the reaction mixture subsequent to
catalytic diboration. After heating at 80 °C for eight
hours, an additional four equivalents of TMSCHN2 were
added and the reaction heated an additional 8 hours. Oxi-
dation of the reaction mixture provided a 58% yield of 1-
trimethylsilyl-1,3-nonanediol (Table 1, entry 1). Analysis
of the crude 1H NMR spectrum indicated that the primary
C–B bond reacted exclusively and that the secondary C–
B bond remained untouched.
By effecting the transformation of simple alkenes into
alkyl 1,2-bis(boronates), the rhodium-catalyzed dibora-
tion of olefins may enable the transformation of olefins
into a variety of functional substructures.1 Whereas the
domino diboration–oxidation reaction sequence effective-
ly delivers 1,2-diols from alkenes in an asymmetric fash-
ion, other transformations may furnish different
structures.2 In this regard, we have begun to develop alter-
nate reaction sequences and have reported that the domino
diboration–Suzuki coupling–oxidation reaction sequence
is particularly effective for transforming 1-alkenes into
chiral b-phenethyl alcohol derivatives.3 This reaction se-
quence relies on the fact that, in Pd-catalyzed cross-cou-
pling, less hindered C–B bonds react faster than more
hindered C–B bonds thereby allowing the selective trans-
formation of one of the two boron atoms in a diboration
product.4
Recently, Mioskowski has described a novel homologa-
tion reaction upon treatment of catechol boronate esters
with TMSCHN2.5,6 We expected that, similar to the Suzu-
ki cross-coupling reaction mentioned above, the Mios-
kowski homologation might also be sensitive to
substitution of the C–B bond and might therefore allow
for the selective production of alkyl 1,3-bis(boronates)
from alkyl 1,2-bis(boronates). In addition, since the Rh-
catalyzed alkene diboration provides catechol boronate
esters directly, we considered that development of a sin-
gle-pot process such as that depicted in Scheme 1 would
be possible and would significantly expand the range of
chiral targets, which are accessible from the asymmetric
diboration reaction.
1. Rh(I)–QUINAP
B2(cat)2
OH OH
toluene, 12 h
R
R
TMS
2. TMSCHN2 (8 equiv)
80 °C, 16 h
3. NaOH/H2O2
Scheme 2
With experimental conditions for domino diboration–ho-
mologation developed, several terminal alkenes were ex-
plored in the tandem reaction (Table 1). Whereas styrene
is a poor substrate for the domino sequence (entry 6), ali-
phatic alkenes appear to provide consistently higher
yields (45–58%) regardless of substitution of the allylic
carbon. In all cases, the 1-trimethylsilyl-1,3-diols were
Initial experiments were directed towards developing the
domino diboration–homologation–oxidation sequence
and towards learning about the homologation selectivity
SYNLETT 2005, No. 11, pp 1749–1751
0
7
.0
7
.2
0
0
5
Advanced online publication: 09.06.2005
DOI: 10.1055/s-2005-869873; Art ID: S03805ST
© Georg Thieme Verlag Stuttgart · New York

1750
D. M. Kalendra et al.
LETTER
+
N2
Table 1 Single-Pot Domino Diboration–Homologation–Oxidation
–
TMS
R
B(cat)
B(cat)
TMSCHN2
Entry
R
Yield (%)
(cat)B
TMS
B(cat)
R
1
2
3
4
5
6
hexyl
58
49
51
55
53
15
A
tert-butyl
neopentyl
cyclohexyl
isobutyl
Phenyl
(cat)B
B(cat)
R
+
N2
TMS
(cat)B
B(cat)
TMS
(cat)B
R
–
B(cat)
R
TMSCHN2
B
Scheme 3
isolated by column chromatography as a mixture of dia-
stereomers.7
the more substituted carbon, presumably for electronic
reasons.9
Because the Rh–QUINAP-catalyzed diboration is highly
enantioselective when the allylic carbon of the 1-alkene is
a quaternary center, the domino single-pot diboration–ho-
mologation–oxidation procedure may be used to generate
optically active products with useful levels of selectivity.
As depicted in Equation 1, TBAF-promoted protodesily-
lation of the product derived from tert-butylethylene pro-
vides the 1,3-diol in 93% enantiomeric excess.8
Comparing this level of selectivity with that of the 1,2-
diol obtained by diboration–oxidation (94% ee,
Equation 2) suggests that the homologation reaction does
not disturb the configuration of the stereogenic C–B bond
in the reaction intermediate and that the level of selectivi-
ty obtained in the diboration reaction is manifest in the
diboration–homologation–oxidation product.
In summary, we have described the operationally simple,
one-pot diboration–homologation–oxidation reaction of
olefin substrates. Current efforts in our laboratory focus
on developing other transformations of 1,2-bis(boronate)
intermediates.
Acknowledgment
This work was supported by the NIH (GM 59417). JPM is a fellow
of the Alfred P. Sloan foundation and thanks AstraZeneca, Bristol-
Myers Squibb, DuPont, GlaxoSmithKline and the Packard Founda-
tion for support.
References
OH OH
TMS
OH OH
TBAF
80 °C
(1) For enantioselective catalytic diboration, see: (a)Morgan, J.
B.; Miller, S. P.; Morken, J. P. J. Am. Chem. Soc. 2003, 125,
8702. For Rh-catalyzed diboration of alkenes, see:
(b) Baker, R. T.; Nguyen, P.; Marder, T. B.; Westcott, S. A.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1336. (c) Dai, C.;
Robins, E. G.; Scott, A. J.; Clegg, W.; Yufit, D. S.; Howard,
J. A. K.; Marder, T. B. Chem. Commun. 1998, 1983.
(d) Nguyen, P.; Coapes, R. B.; Woodward, A. D.; Taylor, N.
J.; Burke, J. M.; Howard, J. A. K.; Marder, T. B. J.
Organomet. Chem. 2002, 652, 77. For Pt-catalyzed
diboration of alkenes, see: (e) Iverson, C. N.; Smith, M. R.
III Organometallics 1997, 16, 2757. (f) Ishiyama, T.;
Yamamoto, M.; Miyaura, N. Chem. Commun. 1997, 689.
(g) Marder, T. B.; Norman, N. C.; Rice, C. R. Tetrahedron
Lett. 1998, 39, 155. (h) Ishiyama, T.; Momota, S.; Miyaura,
N. Synlett 1999, 1790.
Me
Me
Me
Me
Me
Me
38% yield
93% ee
obtained with
(R)–QUINAP
Equation 1
Rh(I)
(R)–QUINAP
OH
B2(cat)2
Me
Me
Me
OH
then H2O2
Me
Me
Me
47% yield
94% ee
Equation 2
(2) (a) Hydrogen peroxide and NaOH is most commonly used
for oxidation of C–B bonds: Zweifel, G.; Brown, H. C. Org.
React. 1963, 13, 1. (b) A number of other oxidants have also
been employed for this purpose, see: Kabalka, G. W.;
Wadgaonkar, P. P.; Shoup, T. M. Organometallics 1990, 9,
1316; and references cited therein.
One of two explanations might account for the level and
sense of regioselection in the homologation reactions de-
scribed above. As depicted in Scheme 3, it is conceivable
that TMSCHN2 adds to the less hindered C–B bond (to
give B) fastest and the resulting 1,2-alkyl shift provides
the observed product in a selective fashion. Alternatively,
it is tenable that addition of TMSCHN2 to the boronate is
reversible and that the rate of the subsequent rearrange-
ment dictates the reaction outcome. The former scenario
appears more plausible given that 1,2-alkyl shifts involv-
ing boronate complexes are known to favor migration of
(3) Miller, S. P.; Morgan, J. B.; Nepveux, F. J.; Morken, J. P.
Org. Lett. 2004, 6, 131.
(4) For examples of cross-coupling with secondary C–B bonds,
see: (a) Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem.
Int. Ed. 2002, 41, 1945. (b) Kataoka, N.; Shelby, Q.;
Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67, 5553.
(5) Goddard, J.-P.; Le Gall, T.; Mioskowski, C. Org. Lett. 2000,
2, 1455.
Synlett 2005, No. 11, 1749–1751 © Thieme Stuttgart · New York

LETTER
Single-Pot Domino Diboration–Homologation
1751
(6) For lead references to other homologations, see:
(a) Matteson, D. S.; Majumdar, D. J. Am. Chem. Soc. 1980,
102, 7590. (b) Matteson, D. S.; Majumdar, D.
of trimethylsilyldiazomethane (2.0 M in hexanes) was
added. After stirring for 8 h at 80 °C an additional 0.50 mL
(1.0 mmol) of trimethylsilyldiazomethane (2.0 M in
hexanes) was added. After stirring an additional 8 h at 80 °C,
the solution was cooled to 0 °C and NaOH (1.0 mL of 3 M)
and H2O2 (1 mL of 30% solution) were added cautiously.
After 6 h, the mixture was treated with 2 mL of sat. aq
Na2S2O3 and extracted with EtOAc. The crude material was
purified by silica gel chromatography (3:1 hexanes–EtOAc)
to provide 25 mg (49% yield) of pure 4,4-dimethyl-1-
(trimethylsilyl)pentane-1,3-diol.
Organometallics 1983, 2, 1529. (c) Chen, A.; Ren, L.;
Crudden, C. M. J. Org. Chem. 1999, 64, 9704. (d) Tsai, D.
J. S.; Matteson, D. S. Organometallics 1983, 2, 236.
(e) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4,
1687. (f) Hara, S.; Satoh, Y.; Suzuki, A. Chem. Lett. 1982,
1289. (g) Leung, T.; Zweifel, G. J. Am. Chem. Soc. 1974, 96,
5620. (h) Brown, H. C.; Singh, S. M. Organometallics 1986,
5, 994. (i) For diastereoselective homologation of C–B
bonds with prochiral homologation reagents, see: Hoffmann,
R. W.; Stiasny, H. C. Tetrahedron Lett. 1995, 36, 4595.
(7) Representative Procedure.
(8) Procedure for Protodesilylation.
To 38 mg of 4,4-dimethyl-1-(trimethylsilyl)pentane-1,3-diol
(0.19 mmol, obtained from entry 2, Table 1) was added 2.4
mL of THF followed by 0.38 mL of TBAF (1.0 M in THF,
0.38 mmol). After stirring at 70 °C for 23 h the mixture was
evaporated to dryness and the residue resuspended in
EtOAc. After washing with H2O, the solution was
concentrated and the crude material purified on silica gel
(2:1 hexanes–EtOAc) to give 9.4 mg (38% yield) of 4,4-
dimethyl-1,3-pentanediol.
A dry 16 mL vial was charged with 3.7 mg (0.013 mmol) of
{bicyclo[2.2.1]hepta-2,5-diene}-(2,4-pentanedionato)-
rhodium(I), 5.5 mg (0.013 mmol) of (S)-QUINAP, and 1.0
mL of toluene in a dry-box. The resultant solution was
stirred for 3 min before 89 mg (0.37 mmol) of
bis(catecholato)diboron was added. After 3 more minutes,
32 mL (0.25 mmol) of 3,3-dimethyl-1-butene was added and
the solution allowed to stir for 24 h at ambient temperature.
The vial was then wrapped in foil and 0.50 mL (1.0 mmol)
(9) Soderquist, J. A.; Najafi, M. R. J. Org. Chem. 1986, 51,
1330.
Synlett 2005, No. 11, 1749–1751 © Thieme Stuttgart · New York