B-allenyl- and B-(γ-trimethylsilylpropargyl)-10-phenyl-9- borabicyclo[3.3.2]decanes: Asymmetric synthesis of propargyl and α-allenyl 3°-carbinols from ketones

Article abstract of DOI:10.1021/ol061596j

Simple and efficient Grignard procedures are reported for the syntheses of B-allenyl-10-(phenyl)-9-borabicyclo[3.3.2]decane (1) and its B-(γ-trimethylsilylpropargyl) counterpart (2) in both enantiomeric forms. Both add selectively to ketones, providing propargyl- and α-silylallenyl 3°-carbinols, respectively (i.e., 6 (61-93% ee) and 9 (64-98% ee)). The air-stable boron byproduct is efficiently recovered and recycled back to either 1 or 2. The ozonolysis and bromination of 9 provide nonracemic α-hydroxy acids and γ-bromopropynyl carbinols, respectively.

Full text of DOI:10.1021/ol061596j

ORGANIC
LETTERS
2006
Vol. 8, No. 18
4089-4091
B-Allenyl- and
B-( -Trimethylsilylpropargyl)-
10-phenyl-9-borabicyclo[3.3.2]decanes:
Asymmetric Synthesis of Propargyl and
γ
r
-Allenyl 3°-Carbinols from Ketones
Eliud Hernandez, Carlos H. Burgos, Eyleen Alicea, and John A. Soderquist*
UniVersity of Puerto Rico, Department of Chemistry,
Rio Piedras, Puerto Rico 00931-3346
jas@janice.uprr.pr
Received June 28, 2006
ABSTRACT
Simple and efficient Grignard procedures are reported for the syntheses of B-allenyl-10-(phenyl)-9-borabicyclo[3.3.2]decane (1) and its B-(
trimethylsilylpropargyl) counterpart (2) in both enantiomeric forms. Both add selectively to ketones, providing propargyl- and -silylallenyl
-carbinols, respectively (i.e., 6 (61 93% ee) and 9 (64 98% ee)). The air-stable boron byproduct is efficiently recovered and recycled back
γ-
r
3
°
−
−
to either 1 or 2. The ozonolysis and bromination of 9 provide nonracemic
r-hydroxy acids and γ-bromopropynyl carbinols, respectively.
Recently, we reported the asymmetric allenyl- and propar-
gylboration of aldehydes with the 10-trimethylsilyl-9-
borabicyclo[3.3.2]decanes (10-TMS-9-BBDs).1 These new
reagents provide efficient syntheses of nonracemic propar-
gylic and R-allenylic carbinols, respectively. Moreover, the
robust, rigid, and recyclable nature of the BBD ring system
makes these systems highly attractive alternatives to other
methods.2 Neither process is known for prochiral ketones.3
The success of these and related SE2′ processes requires the
formation of isomerically pure allenyl- or propargylborane
reagents, and Grignard procedures are now available for both.
In related studies, we discovered that for asymmetric
allylboration, the 10-TMS-9-BBD reagents are effective for
aldehydes, whereas the corresponding 10-Ph-9-BBD reagents
are effective for ketones.4 We now wish to report the
preparation of both enantiomerically pure forms of B-allenyl-
10-Ph-9-BBD (1) and γ-trimethylsilyl-propargyl-10-Ph-9-
BBD (2) and their additions to prochiral ketones for the
highly selective asymmetric syntheses of propargyl- (5) and
R-allenyl- (9) 3°-carbinols, respectively.
The thermally stable (()-B-MeO-10-Ph-9-BBD (3), readily
prepared from B-MeO-9-BBN, serves as a very convenient
precursor to both (+)-4S and (-)-4R as pure crystalline
(1) (a) Hernandez, E.; Soderquist, J. A. Org. Lett. 2005, 70, 5397. (b)
Lai, C.; Soderquist, J. A. Org. Lett. 2005, 7, 799. See also: (c) Burgos, C.
H.; Canales, E.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc. 2005, 127,
8044.
(2) (a) Ikeda, N.; Arai, I.; Yamamoto, H. J. Am. Chem. Soc. 1986, 108,
483-486. (b) Haruta, R.; Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Am.
Chem. Soc. 1982, 104, 7667-7669. (c) Corey, E. J.; Yu, C.-M.; Lee, D.-
H. J. Am. Chem. Soc. 1990, 112, 878. (d) Brown, H. C.; Khire, U. R.;
Narla, G. J. Org. Chem. 1995, 60, 8130. (e) Kulkarni, S. V.; Brown, H. C.
Tetrahedron Lett. 1996, 37, 4125.
(3) For racemic processes, see: (a) Zweifel, G.; Backlund, S. J.; Leung,
T. J. Am. Chem. Soc. 1978, 100, 5561. (b) Wang, K. K.; Nikam, S. S.; Ho,
C. D. J. Org. Chem. 1983, 48, 5376. (c) Wang, K. K.; Liu, C. J. Org.
Chem. 1985, 50, 2578. (d) Brown, H. C.; Khire, U. R.; Narla, G. J. Org.
Chem. 1995, 60, 8130. With chiral substrates, see: Alcaide, B.; Almendros,
P.; Aragoncillo, C.; Rodriguez-Acebes, R. J. Org. Chem. 2001, 66, 5208.
(4) Canales, E.; Prasad, G.; Soderquist, J. A. J. Am. Chem. Soc. 2005,
127, 11572.
10.1021/ol061596j CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/03/2006

compounds, with a combined total yield of 67%.4 These
complexes are air-stable and can be stored indefinitely. The
reagents 1 were readily prepared in optically pure forms
through the addition of allenylmagnesium bromide to the
N-methylpseudoephedrine (NMPE) borinic ester complexes
4 (84%; Scheme 1).5 The Grignard reagent derived from
1). However, with propiophenone, the addition is much
slower (2 d, 25 °C), with 5b being produced in 76% ee.
Notably, even very challenging substrates such as 2-butanone
and methyl vinyl ketone give 6 with highly respectable levels
of selectivities (i.e., 74 (c) and 61% (h) ee, respectively).
Encouraged by these very positive results with the alle-
nylboration of ketones with 1, we turned our attention to
the corresponding propargylboration of representative ketones
with 2. Based on our earlier studies with the propargyl-
versus allenylboration of aldehydes with the corresponding
10-TMS-9-BBD systems,1 we expected even higher enan-
tioselectivities from 2 than we had observed with 1.
Scheme 1
The asymmetric propargylboration of representative ke-
tones was examined with 2 in THF at -78 °C and found to
provide good to excellent yields (62-95%) of the corre-
sponding R-allenyl 3°-carbinols 9, with methyl ketones
generally exhibiting high selectivities (78-98% ee; Table
Table 2. . Propargylboration of RLRSCO with 2
3-bromo-1-TMS-1-propyne was also found to cleanly add
to 4 to provide either (-)-2R or (+)-2S (97%; Scheme 1).
The asymmetric allenylboration of representative ketones
was examined with 1. Rapid reaction is observed with methyl
ketones (3-12 h, -78 °C). The resulting 3°-carbinols 6 are
obtained efficiently (62-85%) in high ee (61-93%; Table
Table 1. Allenylboration of RLRSCO with 1
% eeb
(abs config)c
RL
RS
1
series
9a (%)
Ph
Bu
c-C6H9
p-MeOC6H4
p-BrC6H4
p-O2NC6H4
2-C4H3Se
2-C4H3Oe
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Et
S
S
S
R
S
S
S
S
S
a
b
c
d
e
f
g
h
i
81
62
67
95
80
79
71
82
63
97 (R)d
84 (R)
91 (R)
92 (S)
98 (R)
98 (R)
78 (S)
80 (R)
64 (R)
e
% eeb
(abs config)
a In each case, the crystalline byproduct 8 was recovered (50-85%) using
a pseudoephedrine (PE) workup (i.e., (1R,2R)-(-)-PE for (+)-8S and
(1S,2S)-(+)-PE for (-)-8R). This process is both more economical and more
convenient than with NMPE, which is not currently available in both
enantiomeric forms. Moreover, 8 is easily converted back to 2 (>95%)
through the same general Grignard procedure used for 4. b Product ee was
determined by reaction of 8 with phosphorus CDA and analysis by 31P
NMR. c Configuration predicted by analogy to 9a. d Allenic alcohol 9a was
converted to the known 2-hydroxy-2-phenylpropionic acid and the sign of
rotation was compared with the reported value. e 1-Cyclohexenyl, 2-thienyl,
and 2-furyl.
RL
RS
1
series
6a (%)
Ph
Ph
Ph
Et
Bu
i-Pr
t-Bu
TMS
CH2dCH
Me
Me
Et
Me
Me
Me
Me
Me
Me
S
R
R
R
S
R
S
S
S
a
a
b
c
d
e
f
74
85
65
71
80
71
66
62
64
91 (S)
93 (R)
76 (R)
74 (S)
81 (R)
84 (R)
83 (S)
90 (R)
61 (S)
g
h
a The a series was performed with both (-)-1R and (+)-1S. The aS, b,
f, and h series were conducted employing an oxidative workup. For the
remaining examples, the intermediate 5 was isolated and converted to 6
and either 4 or 8 was recovered (69-81%) via the NMPE workup procedure.
b Product ee determined by conversion to the Alexakis esters6 and analysis
by 31P NMR.
2). Reaction times for these substrates varied considerably
from 3 to 36 h for the methyl ketones. The aryl ketones,
(5) Short, R. P.; Masamune, S. J. Am. Chem. Soc. 1989, 111, 1892.
(6) Alexakis, A.; Frutos, J. C.; Mutti, S.; Mangeney, P. J. Org. Chem.
1994, 59, 3326.
4090
Org. Lett., Vol. 8, No. 18, 2006

containing electron-withdrawing groups (i.e., Table 2, series
e and f) were the slowest in this group. Even less reactive is
the ethyl ketone, propiophenone, whose propargylation
requires 52 h at -78 °C. However, even highly demanding
substrates, such as 2-hexanone, give 9 with high selectivity
(i.e., 9b, 84% ee).
The absolute stereochemistry for 9a was determined by
its conversion to the known atrolactic acid (12) through
simple ozonolysis (Scheme 2). This oxidation is greatly
discover other potential applications for this R-silylallenyl
functionality, we examined the NBS-mediated bromodesi-
lylation of 9a,j together with two examples of O-Ac
2°-carbinols 9k,l. The reactions are highly regioselective
producing the corresponding propargyl bromides 13 cleanly
in nonracemic form. This simple synthesis of these interesting
polyfunctional compounds represents another useful feature
of the TMS substitution3b,c in 2 which leads to 9.
As previously described,4 the 10-substituted-9-BBD ring
clearly defines a “chiral pocket”, as illustrated in the
energetically favored pre-transition state complexes A and
A′ (see below) for the allenyl- and propargylboration
processes with the reagents 1R and 2R, respectively. Because
BBD systems are stable, easily prepared in either enantio-
merically pure form, highly reactive, environmentally friendly,
recyclable, and exhibit high selectivities over a wide range
of unsymmetrical ketones, their applications to the asym-
metric allenyl- and propargylboration to ketones represent
highly useful new processes.
Scheme 2
Acknowledgment. The support of the NSF (CHE-
0517194), and NIH (S06GM8102) is gratefully acknowl-
edged.
Supporting Information Available: Full experimental
procedures, analytical data, and selected spectra for 1, 2, 6,
9-13, and derivatives (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
facilitated by the R-TMS substitution in 9, which permits
the ozonolysis to proceed directly to 11 through 10.1a To
OL061596J
Org. Lett., Vol. 8, No. 18, 2006
4091