Asymmetric synthesis of 2°- and 3°-carbinols via B-methallyl-10-(TMS and Ph)-9-borabicyclo[3.3.2]decanes

Article abstract of DOI:10.1021/jo701633k

(Chemical Equation Presented) Simple Grignard procedures provide methallylboranes 1a and 1b in enantiomerically pure form from air-stable precursors in 98% and 95% yields, respectively. These reagents add smoothly to aldehydes and methyl ketones, respecti

Full text of DOI:10.1021/jo701633k

types of “allylation” processes,2 but for ketone substrates, the
only successful methallylation was recently reported employing
tetrakis(methallyl)tin and a (R)-H8-BINOL/Ti catalyst.3 This
method uses 6 equiv of the toxic methallyltin moiety, a large
catalyst loading (30 mol %), and exhibits modest to good
enantioselectivity (46-90% ee). Since asymmetric methallyla-
tion is an important synthetic process,4 we felt that a better,
more selective and user-friendly process would represent an
important advance. We envisaged that the methallylation of both
aldehydes and ketones could be markedly improved through
the use of the 10-substituted-9-borabicyclo[3.3.2]decanes which
are easy to handle, effectively recovered and recycled, and
available in both enantiomeric forms.
Asymmetric Synthesis of 2°- and 3°-Carbinols via
B-Methallyl-10-(TMS and
Ph)-9-borabicyclo[3.3.2]decanes†
Jose´ G. Roma´n and John A. Soderquist*
Department of Chemistry, UniVersity of Puerto Rico, Rio
Piedras, Puerto Rico 00931-3346
jas@janice.uprr.pr
ReceiVed August 1, 2007
Recently, we reported the synthesis of the B-allyl-10-TMS-
and -10-Ph-BBD systems (2) and their highly selective additions
to aldehydes5 and ketones,6 respectively. The corresponding
B-methallyl reagents 1 were envisaged as very attractive
alternatives for the methallylboration of either aldehydes or
ketones, depending upon the choice of the 10-substituent
employed.
The air-stable crystalline pseudoephedrine (PE) complexes
4a serve as efficient precursors to 2a (98%) through simple
Grignard procedures.5 However, the analogous process with 4a
and methallylmagnesium chloride (0.5 M in THF) proved to
be both sluggish and inefficient. Fortunately, the more reactive
B-OMe derivatives 3a, which are readily prepared from 2a
(87%),5a provide an efficient entry to 1a through this Grignard
method (98%) (Scheme 1).
Reagents 1a react smoothly with aldehydes to yield pure
3-methyl homoallylic alcohols 6 efficiently (69-89%) with
excellent selectivities (94-99% ee) (Scheme 2, Table 1). The
product ee values were determined by their conversion to their
Alexakis esters and analysis through 31P NMR.7 Similar to
allylboration,5 this process is quite general, being effective for
alkyl, aryl, substituted aryl, heteroaryl, and unsaturated alde-
hydes. Our protocol includes the isolation of the borinic ester
intermediates 5 in essentially quantitative yields following the
removal of the solvents. A non-oxidative workup procedure was
employed that permits the recovery of the air-stable pseu-
doephedrine (PE) complexes 4a (62-78%), which can be
converted back to 1a (Scheme 1).
Simple Grignard procedures provide methallylboranes 1a and
1b in enantiomerically pure form from air-stable precursors
in 98% and 95% yields, respectively. These reagents add
smoothly to aldehydes and methyl ketones, respectively,
providing branched 2°- (6, 69-89%, 94-99% ee) and 3°-
(10, 71-87%, 74-96% ee) homoallylic alcohols.
The asymmetric allylboration of aldehydes remains as one
of the most powerful processes for the preparation of nonracemic
2°-homoallylic alcohols.1 In 1978, Hoffmann1a,c reported the
first enantioselective synthesis of branched 2°-homoallylic
alcohols employing a methallyl derivative of his camphor-
derived boronic esters. Unfortunately, low enantioselectivity is
generally observed with these reagents (40-76% ee). Brown’s
diisopinocampheylborane reagents proved to be more selective
(90-96% ee), but the preparation of these reagents from high-
purity air-sensitive organoborane precursors through organo-
lithium procedures presents operational difficulties.1d,o More-
over, these reagents are ineffective for the allylation of ketones.1e
A variety of alternative processes are now available for these
The competitive reaction of 1a and 2a with benzaldehyde
(1:1:1) was conducted at -78 °C. This reveals that 2a is only
† This work is dedicated to Professor Alfred Hassner on the occasion of his
77th birthday.
(2) (a) Wu, T. R.; Shen, L.; Chong, J. M. Org. Lett. 2004, 6, 2701. (b)
Keck, G. E.; Krishnamurthy, D. Org. Synth. 1998, 75, 12. (c) Yamamoto,
H.; Ishiba, A.; Nakashima, H.; Yanagisawa, A. J. Am. Chem. Soc. 1996,
118, 4723. (d) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833. (e) Loh, T.-
P.; Zhou, J. R.; Li, X. R. Tetrahedron Lett. 1999, 40, 9333. (f) Pu, L.; Yu,
H.-B. Chem. ReV. 2001, 101, 757. (g) Pu, L. Tetrahedron 2003, 59, 9873.
(h) Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763.
(1) (a) Herold, T.; Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1978,
17, 768. (b) Herold, T.; Schrott, C.; Hoffmann, R. W. Chem. Ber. 1981,
114, 359. (c) Hoffmann, R. W.; Herold, T. Chem. Ber. 1981, 114, 375. (d)
Brown, H. C.; Jadhav, P. K.; Perumal, P. T. Tetrahedron Lett. 1984, 25,
5111-5114. (e) Brown, H. C.; Jadhav, P. K.; Perumal, P. T. J. Org. Chem.
1986, 51, 432. (f) Masamune, S.; Short, R. P. J. Am. Chem. Soc. 1989,
111, 1892. See also: (g) Ramachandran, P. V. Aldrichim. Acta 2002, 35,
23 and references cited therein. (h) Flamme, E. M.; Roush, W. R. J. Am.
Chem. Soc. 2002, 124, 13644. (i) Yakelis, N. A.; Roush, W. R. J. Org.
Chem. 2003, 68, 3838. (j) Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2003,
125, 9308. (k) Morgan, J. B.; Morken, J. P. Org. Lett. 2003, 5, 2573. (l)
Barrett, A. G. M.; Braddock, D. C.; de Koning, P. D.; White, A. J. P.;
Williams, D. J. J. Org. Chem. 2000, 65, 375. (m) Barrett, A. G. M.; Beall,
J. C.; Braddock, D. C.; Flack, K.; Gibson, V. C.; Salter, M. M. J. Org.
Chem. 2000, 65, 6508. (n) Corey, E. J.; Yu, C.; Kim, S. S. J. Am. Chem.
Soc. 1989, 111, 5495. (o) Brown, H. C.; Racherla, U. S.; Liao, Y.; Khanna,
V. V. J. Org. Chem. 1992, 57, 6608.
(3) (a) Walsh, P. J.; Kim, J. G.; Camp, E. H. Org. Lett. 2006, 7, 4413.
See also: (b) Ka¨llstro¨m, S.; Jagt, R. B.; Sillanpa¨a¨, R.; Feringa, B. L.;
Minnaard, A. J.; Leino, R. Eur. J. Org. Chem. 2006, 3826.
(4) (a) Nelson, S. G.; Cheung, S. W.; Kassick, A. J.; Hilfiker, M. A. J.
Am. Chem. Soc. 2002, 124, 13654. (b) De Brabander, J. K.; Garc´ıa-Fortanet,
J.; Jiang, X. J. Am. Chem. Soc. 2005, 127, 11254. (c) Nakada, M.; Suzuki,
T.; Inoue, M. J. Am. Chem. Soc. 2003, 125, 1140.
(5) (a) Burgos, C. H.; Canales, E.; Matos, K.; Soderquist, J. A. J. Am.
Chem. Soc. 2005, 127, 8044. (b) Available from Sigma-Aldrich, Inc.
(6) Canales, E.; Prasad, G.; Soderquist, J. A. J. Am. Chem. Soc. 2005,
127, 11572.
(7) Alexakis, A.; Mutti, S.; Mangeney, P. J. Org. Chem. 1992, 57, 1224.
10.1021/jo701633k CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/14/2007
9772
J. Org. Chem. 2007, 72, 9772-9775

TABLE 1. Methallylboration of Aldehydes with 1a
SCHEME 3. Asymmetric Allylboration of Benzaldimine
with 1a
ee,a %
R in RCHO
series
1a
4a (%)
6, %
abs configc
Phd
a
b
c
d
e
f
S, R
S
R
R
R
73, 75
66
66
70
62
78, 80
78
69
89
88
95; (S),(R)
98;b (S)
99; (R)
94; (R)
96; (R)
97; (S)
4-MeOC6H4
4-NO2C6H4
2-ClC6H4
pyridyl
i-Pr
S
74
75
t-Bu
trans-crotyl
g
h
R
R
65
78
73
85
94; (R)
94; (R)
a Enantiomeric excesses were determined by conversion to Alexakis esters
and 31P NMR analysis.7 b Enantiomeric excess was determined by 13C NMR
analysis of the Mosher ester. c The absolute configuration of the alcohols
was determined by a direct comparison of optical rotations obtained to those
reported in the literature.1c,d,2b d This run was performed with both (+)-
1Sa and (-)-1Ra.
SCHEME 4. Asymmetric Allylboration of Ketones with 1b
SCHEME 1. Preparation of Methallylborane 1
1 h, the formation of the aminoborane 8 was complete as
determined by 11B NMR (δ 46). Acidic hydrolysis (2 M HCl)
followed by a basic workup affords the homoallylic amine 9
(73%), in only modest enantioselectivity (38% ee) (Scheme 3).
While disappointing, the lowered observed selectivities for this
and related additions to aldimines vs aldehydes appears to be a
general phenomenon attributable to the larger relative size of
NH vs O.12
SCHEME 2. Asymmetric Allylboration of Aldehydes with
1a
In contrast to the sluggish reaction of methallylmagnesium
chloride with 4a, this Grignard reagent does readily add to the
crystalline pseudoephedrine complex,6 (+)-4Rb, to provide pure
B-methallyl-10-Ph-9-BBD ((-)-1Rb) directly in excellent yield
(95%) (Scheme 4). The enantiomer, (+)-1Sb, was similarly
prepared from the corresponding N-methylpseudoephedrine
complex, (+)-4′Sb.6 The asymmetric methallylboration of
representative methyl ketones was examined with 1b. These
reagents (-)-1Rb and (+)-1Sb undergo clean addition even to
hindered methyl ketones (entry 3d) in e3 h at -78 °C providing
the desired 3°-carbinols 10 with excellent enantioselectivities
(74-96% ee) (Table 2). An oxidative workup (NaOH, H2O2)
was normally used in this protocol. A non-oxidative procedure
employing N-methylpseudoephedrine was developed for the
10Sa example resulting in a 76% yield of recovered (+)-4′Sb.
Similarly, for 10Rb, a pseudoephedrine workup gave crystalline
(+)-4Rb in 71% yield.
slightly more reactive than 1a (i.e., 1.3:1.0), a result that is likely
to be steric in origin.
Homoallylic amines provide important building blocks for
the synthesis of numerous nitrogen-containing natural products.8
While the methallylboration of N-metallo imines is unknown,9
the corresponding allylboration process has been extensively
studied.10-12 We chose to examine this process through the
generation of N-H benzaldimine with MeOH (1 equiv) from its
N-TMS precursor in the presence of 1a in THF at -78 °C. After
(10) (a) Itsuno, S.; Watanabe, K.; Koichi, I.; El-Shehawy, A.; Sarhan,
A. Angew. Chem., Int. Ed. Engl. 1997, 36,109. (b) Wantanabe, K.; Ito, K.;
Itsuno, S. Tetrahedron: Asymmetry 1995, 6, 1531. (c) Wantanabe, K.;
Kuroda, S.; Yokoi, A.; Ito, K; Itsuno, S. J. Organomet. Chem. 1999, 581,
103.
(8) (a) Nicolaou, K. C.; Van Delf, F. L.; Mitchel, H. J.; Rodr´ıguez, R.
M.; Rudsan, F. Angew. Chem., Int. Ed. Engl. 1999, 37, 1871. (b) Schmidt,
U.; Schmidt, J. Synthesis 1994, 300. (c) Ciufolini, M. A.; Hermann, C. W.;
Whitmire, K. H.; Byrne, N. E. J. Am. Chem. Soc. 1989, 111, 3473.
(9) For a recent review see: Felpin, F.-X.; Lebreton, J. Eur. J. Org. Chem.
2003, 3693.
(11) Brown, H. C.; Chen, G. M.; Ramachandran, P. V. Angew. Chem.,
Int. Ed. 1999, 38, 825.
(12) (a) Hernandez, E.; Canales, E.; Gonzalez, E.; Soderquist, J. A. Pure
Appl. Chem .2006, 78, 1389. (b) Hernandez, E.; Canales, E.; Soderquist, J.
A. J. Am. Chem. Soc. 2006, 128, 8712. See also: (c) Gonzalez, A. Z.;
Soderquist, J. A. Org. Lett. 2007, 9, 1081.
J. Org. Chem, Vol. 72, No. 25, 2007 9773

TABLE 2. Methallylboration of Ketones with 1b
one system can be modified for the effective methallylation of
either aldehydes or ketones. This new method can be used with
either an oxidative or non-oxidative workup, the latter process
providing the recovered chiral borane as an air-stable and
recyclable complex 4. Ozonolysis of 6 and 10 provides
â-hydroxyalkyl methyl ketones 7 and 11 efficiently in high
enantiomeric purity.
ee,a %
R in RCOCH3
Ph
10
1b
yield, %
abs configb
a
b
c
S
R
S
S
87 (80)c
71 (69)c
81
88; S
93; R
74; S
96; S
4-NO2C6H4
trans-PhCHdCH
t-Bu
d
75
a Enantiomeric excesses were determined by conversion to Alexakis esters
and 31P NMR.7 b The absolute configuration of the alcohols was determined
by a direct comparison of optical rotations obtained to those reported in
the literature.3a c Yields in parentheses for 10Sa and 10Rb were obtained
employing a non-oxidative workup (the complexes (+)-4′Sb and (+)-4Rb
were also recovered in 76% and 71% yield, respectively).
Experimental Section
B-Methallyl-10R-trimethylsilyl-9-borabicyclo[3.3.2]decane-
((-)-1Ra). A solution of (-)-3R (0.71 g, 3.0 mmol) in hexane (12
mL) was cooled to 0 °C and a solution of methallylmagnesium
chloride (7.8 mL , 0.5 M in THF) was added dropwise. The solution
was allowed to reach room temperature and was stirred for 1 h.
Then the reaction mixture was cooled to -78 °C and quenched
with TMSCl (0.5 equiv). With use of standard techniques to prevent
the exposure of the borane to the open atmosphere, the solution
was concentrated under vacuum, the residue was washed with
pentane (4 × 10 mL), and these washings were filtered through a
celite pad. Concentration gives 0.77 g (98%) of (-)-1Ra: 1H NMR
(C6D6, 300 MHz) δ 0.23 (s, 9H), 1.02-1.76 (m, 15H), 1.80 (s,
3H), 2.23 (m, 3H), 4.75 (s, 1H), 4.92 (s, 1H); 13C NMR (75 MHz,
C6D6) δ 1.9, 22.2, 25.4, 25.9, 26.2, 29.2, 31.5, 34.2, 34.9, 40.0,
40.9, 110.0, 145.0; 11B NMR (CDCl3) δ 83.7; [R]23D -22.6 (c 1.24,
C6D6). B-Methallyl-10S-trimethylsilyl-9-borabicyclo[3.3.2]decane
((+)-1Sa) is prepared by the same procedure starting with (+)-3S.
FIGURE 1. Proposed models for the most energetically favorable pre-
transition state complexes which explain the observed stereochemistry
in the methallylboration of RCHO with 1a (A) and RCOMe with 1b
(B).
SCHEME 5. Ozonolysis of â-Methyl Homoallylic Alcohols
[R]23 +22.3 (c 1.24, C6D6). HRMS [M + H]+ calcd for C16H31-
D
BSi 263.2368, found 263.2369 m/z.
Representative Procedure for the Allylboration of Aldehydes
with 1a. (-)-(R)-3-Methyl-1-(2-chlorophenyl)-3-buten-1-ol (6Rd):
A solution of (-)-1Ra (0.79 g, 3 mmol) in THF (3 mL) was cooled
to -78 °C and 2-chlorobenzaldehyde (0.42 g, 3.0 mmol) was added
dropwise. After 3 h, the solvents were removed under vacuum to
yield 1.15 g (95%) of the corresponding borinate 5Rd. The (1S,2S)-
(-)-pseudoephedrine (0.50 g, 3.0 mmol) and acetonitrile (7 mL)
were added and the mixture was heated at reflux temperature for
2 h. The crystals were separated and washed with pentane (3 × 10
mL) to yield 0.78 g (70%) of (+)-4Ra. The residue was purified
by column chromatography on silica gel (9:1, hexane:Et2O) to
obtain 0.52 g (88%) of 3-methyl-1-(2-chlorophenyl)-3-buten-1-ol
The asymmetric addition of acetone-derived enolates to
aldehydes occurs with low enantioselectivity.13 The product
â-hydroxy methyl ketones are valuable intermediates in the total
synthesis of macrolide and polyether antibiotics.14 An alternative
to the ineffective aldol route to â-hydroxy methyl ketones with
acetone enolates was introduced by Hoffmann1b through the
ozonolysis of 6. Very recently, Walsh showed that this process
was effective for 10.3a With the higher selectivities observed
with 1 and 10, we chose to demonstrate the synthetic value of
this transformation further with simple examples and to
reconfirm the absolute stereochemistry of 6 and 10 (Scheme
5).
In summary, the new BBD reagents 1 are efficiently prepared
in either enantiomeric form through simple Grignard procedures
that employ air-stable organoborane precursors. Exceeding the
selectivities observed with other reagents and processes, 1
provides either enantiomer of branched 2° (6, 69-89%) and
3°-homoallylic alcohols (10, 71-87%) with predictable stere-
ochemistry (see Figure 1)5,6 and remarkable enantioselectivity
(94-99% and 74-96% ee, respectively). Thus, for the first time,
1
(6Rd). H NMR (CDCl3, 300 MHz) δ 1.86 (s, 3H), 2.23 (dd, J )
13.9 Hz, J ) 9.7 Hz, 1H), 2.52-2.60 (m, 2H), 4.92 (d, J ) 18.7
Hz, 2H), 5.21 (dd, J ) 9.7 Hz, J ) 2.7 Hz, 1H), 7.16-7.34 (m,
3H), 7.61 (dd, J ) 7.7 Hz, J ) 1.4 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ 22.0, 46.6, 67.9, 114.2, 126.9, 127.1, 128.3, 129.3, 131.5,
141.4, 142.5. HRMS [M + H - H2O]+ calcd for C11H12Cl1
179.0622, found 179.0622. The enantiomeric purity was determined
by the CDA reagent developed by Alexakis, using the reported
procedures (31P NMR δ 131 (97, 6Rd), 144 (3, 6Sd)).7 [R]25
+58.54 (c 1.11, CHCl3, 94% ee).
D
Representative Ozonolysis. (S)-4-Hydroxy-4-phenyl-2-bu-
tanone (7): 6Sa (0.14 g, 0.86 mmol) was diluted in MeOH (10
mL) and cooled to -78 °C. To this solution was bubbled ozone
until a blue color persisted (10 min) in the reaction mixture. The
reaction mixture was allowed to reach room temperature and the
excess of ozone was removed under a N2 purge. The solution was
cooled to -78 °C, dimethyl sulfide (0.13 mL) was added dropwise,
and the mixture was stirred overnight slowly reaching room
temperature. The mixture was washed with water (3 × 5 mL). The
organic layer was dried over MgSO4, filtered, and concentrated
under reduced pressure to afford 0.14 g of 7 (98%). 1H NMR
(CDCl3, 300 MHz) δ 2.20 (s, 3H), 2.81 (dd, J ) 3.6 Hz, 18.0 Hz,
1H), 2.90 (dd, J ) 8.7 Hz, J ) 18.0 Hz, 1H), 3.32 (s, broad OH,
1H), 5.15 (dd, J ) 3.7 Hz, J ) 8.7 Hz, 1H), 7.26-7.36 (m, 5H);
13C NMR (CDCl3, 75 MHz) δ 30.7, 51.9, 69.8, 125.6, 127.7, 142.7,
209.0. [R]24D -53.2 (c 2.20, CHCl3) {lit.13 (R) [R]53D +40.9 (c 10.3,
CHCl3, 57% ee) +57.1 (c 1.10, CHCl3)}.
(13) (a) Paterson, I.; Goodman, J. M. Tetrahedron Lett. 1989, 30, 997.
(b) Matsumoto, Y.; Hayashi, T.; Ito, Y. Tetrahedron 1994, 50, 335.
(14) (a) Masamune, S.; Hirama, M.; Mori, S.; Ali, Sk. A.; Garvey, D. S.
J. Am. Chem. Soc. 1981, 103, 1568. (b) Nicolaou, K. C.; Daines, R. A.;
Chakraborty, T. K; Ogawa, T.; Papahatjis, D. P.; Uenishi, J J. Am. Chem.
Soc. 1988, 110, 4660. (c) Nicolaou, K. C.; Daines, R. A.; Chakraborty, T.
K; Ogawa J. Am. Chem. Soc. 1988, 110, 4685.
9774 J. Org. Chem., Vol. 72, No. 25, 2007

(R)-3-Methyl-1-phenyl-3-buten-1-amine (9R): A solution of
(-)-1Ra (0.79 g, 3 mmol) in THF (3 mL) was cooled to -78 °C.
To this solution was added N-TMS benzaldimine (0.62 g, 3.0
mmol)11 followed by dry MeOH (0.16 mL, 4 mmol). After 1 h,
the reaction was warmed to room temperature and the solvents were
removed under vacuum to afford the intermediate aminoborane. A
solution of aqueous HCl (10 mL, 2 M) was added. The mixture
was stirred at room temperature for 1 h. The aqueous phase was
washed with Et2O (2 × 5 mL). The resulting aqueous phase was
neutralized with Na2CO3 followed by Et2O extractions (3 × 15
mL). The organic phase was then dried over MgSO4. Removal of
solvent in vacuo afforded the homoallylic amine 9R (38% ee, 73%
yield). 1H NMR (CDCl3, 300 MHz) δ 1.81 (s, 3H), 2.40 (ddq, J )
13.8 Hz, J ) 9.2 Hz, J ) 4.0 Hz, 2H), 2.42 (s, broad OH, 1H),
4.85-4.86 (m, 1H), 4.90 (dd, J ) 9.2 Hz, J ) 4.1 Hz, 1H), 4.95-
4.97 (m, 1H), 7.54 (d, J ) 8.4 Hz, 1H), 8.18 (d, J ) 8.6 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 22.1, 48.3, 114.9, 123.5, 126.4, 141.3,
147.1, 151.5. The enantiomeric purity was determined by the 31P
NMR CDA reagent developed by Alexakis, using the reported
procedures.7 [R]29D +6.71 (c 1.31, CHCl3, 38% ee). HRMS [M +
H]+ calcd for C11H16N1 162.1277, found 162.1277.
Methallyl-10R-phenyl-9-borabicyclo[3.3.2]decane (1Rb) is prepared
by the same procedure starting with (+)-4Rb (9-(1S,2S-pseu-
doephedrinyl)-(10R)-phenyl-9-borabicyclo[3.3.2]decane).6 [R]27
D
-42.3 (c 1.91, C6D6). Other data are essentially identical with those
for 1Sb.
Representative Procedure for the Allylboration of Ketones
with 1b. (-)-(S)-4-Methyl-2-phenyl-4-penten-2-ol (10Sa): A
solution of (+)-1Sb (0.80 g, 3.0 mmol) in THF (3 mL) was cooled
to -78 °C and acetophenone (0.36 g, 3.0 mmol) was added
dropwise. After 3 h, the temperature of the reaction mixture was
raised to 25 °C and NaOH (2.0 mL, 3 M solution in water) was
added followed by H2O2 (0.9 mL, 30 wt % in water). The biphasic
mixture was refluxed for 2 h followed by an aqueous workup (3 ×
15 mL of brine solution). The combined organic phase was dried
over MgSO4 and filtered. The crude product was then purified by
silica gel column chromatography (4:1, hexane:ethyl acetate) to
obtain 0.46 g of 10Sa (87%). 1H NMR (CDCl3, 300 MHz) δ 1.44
(s, 3H), 1.59 (s, 3H), 2.50 (s, broad OH, 1H), 2.60 (dd, J ) 13.3
Hz, J ) 4.6 Hz, 2H), 4.84 (d, J ) 4.4 Hz, 2H), 7.22-7.50 (m, 5H);
13C NMR (75 MHz, CDCl3) δ 24.1, 30.5, 51.9, 73.1, 115.5, 124.7,
126.4, 127.9, 142.4, 147.8. [R]27D -31.2 (c 1.00, CH2Cl2, 88% ee).
The enantiomeric purity was determined by the CDA reagent
developed by Alexakis, using the reported procedures (31P NMR δ
136.5 (94, 10Sa), 138.0 (6, 10Ra)).7 These data were in complete
agreement with literature values.3a
(+)-B-Methallyl-(10S)-phenyl-9-borabicyclo[3.3.2]decane (1Sb).
To a solution of (+)-4′Sb6 (1.17 g, 3.0 mmol) in hexane (12 mL)
was added freshly prepared methallylmagnesium chloride (9.0 mL,
0.66 M in THF) dropwise. The solution was allowed to stir for
2 h. The reaction mixture was cooled to -78 °C and quenched
with 1.0 equiv of TMSCl. With use of standard techniques to
prevent the exposure of the borane to the open atmosphere, the
solution was concentrated under vacuum, the residue was washed
with pentane (3 × 20 mL), and these washings were filtered through
Acknowledgment. The support of the NSF (CHE-0517194)
and NIH SCORE (S06GM8102) is gratefully acknowledged.
The authors wish to thank Dr. Eda Canales (Harvard University)
for her help with the preparation of this manuscript.
1
a celite pad. Concentration gives 0.76 g (95%) of 1Sb. H NMR
Supporting Information Available: Full experimental proce-
dures, characterization data, and selected spectra for 1-10 and
derivatives. This material is available free of charge via the Internet
at http://pubs.acs.org.
(CDCl3, 300 MHz) δ 1.60-2.71 (m, 20H), 4.57 (s, 1H), 4.80 (s,
1H), 7.15-7.42 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 23.5, 23.6,
25.4, 26.6, 27.9, 29.1, 29.8, 34.2, 39.9, 40.4, 53.3, 109.6, 124.71,
128.1, 129.9, 144.5, 146.7. [R]27 +45.2 (c 2.03, C6D6). HRMS
D
[M]+ calcd for C19H27B 266.2206, found 266.2206 m/z. (-)-B-
JO701633K
J. Org. Chem, Vol. 72, No. 25, 2007 9775