N-Acetylbornane-10,2-sultam: A Useful, Enantiomerically Pure Acetate Synthon for Asymmetric Aldol Reactions

Full text of DOI:10.1021/jo961953b

J . Org. Chem. 1997, 62, 6397-6400
6397
Sch em e 1
N-Acetylbor n a n e-10,2-su lta m : A Usefu l,
En a n tiom er ica lly P u r e Aceta te Syn th on for
Asym m etr ic Ald ol Rea ction s
Silas Bond and Patrick Perlmutter*
Department of Chemistry, Monash University,
Clayton, Victoria, 3168, Australia
Received October 17, 1996
(Revised Manuscript Received May 20, 1997)
In tr od u ction
In a projected synthesis of (+)-blastmycinone1,2 (1, R
) n-Bu) we needed to prepare enantiomerically-pure 2
shown in Scheme 1. We envisaged preparing 2 by a
diastereoselective aldol reaction between an enantiomeri-
cally pure acetate synthon3-5 3 (an enolate of amide 4,
where X*N is a chiral auxiliary) and acrolein (Scheme 1).
As we have had some success with the use of dialkyl-
boron enolates of N-propionylbornane-10,2-sultams (de-
rivatives of “Oppolzer’s sultams”)6 in aldol chemistry,7,8
we decided to employ the corresponding N-acetylbornane-
10,2-sultam9 as a chiral acetate synthon. On examina-
tion of the literature we were surprised to discover that
no additions of the dialkylboron enolates of N-acetylbor-
nane-10,2-sultams9 have been reported.
Sch em e 2
A summary of the aldol chemistry of N-acylbornane-
10,2-sultams6,9-11 is given in Scheme 2. Treatment of the
corresponding (Z)-dialkylboron enolate 66 or silyl ketene
aminal 710 with an aldehyde usually provides aldols 8 or
9, respectively, with high diastereoselectivity.
The only report on the chemistry of the N-acetyl
derivative 5a describes Lewis acid promoted asymmetric
aldol reactions of its corresponding silyl ketene aminals10
(7a , Scheme 2). With regard to the current study it is
important to note that for all these reactions, the relative
stereochemistry at the carbinol center of the major
product in each case is the same, irrespective of the
starting enolate (N-acetyl9 or other acyl6) or the reaction
conditions (dialkyl boron enolate,6 silyl ketene aminal,10
presence11 or absence6 of additional Lewis acid).
Sch em e 3
Resu lts a n d Discu ssion
Thus we decided to examine the reaction of acrolein
with the diethylboron enolate 6a (Scheme 3). We were
pleased to find that this aldol reaction proceeds in quite
acceptable yields. Unlike reactions with the N-propionyl
(1) Birch, A. J .; Cameron, D. W.; Harada, Y.; Rickards, R. W. J .
Chem. Soc. 1961, 889-895.
(2) Li, W.; Nihira, T.; Sakuda, S.; Nishida, T.; Yamada, Y. J . Ferm.
Bioeng. 1992, 74, 214-217.
(3) Otsuka, K.; Ishizuka, T.; Kimura, K.; Kunieda, T. Chem. Pharm.
Bull. 1994, 42, 748-750.
(4) Cooke, J . W. B.; Davies, S. G.; Naylor, A. Tetrahedron 1993, 49,
7955-7966.
(5) Oppolzer, W.; Marco-Contelles, J . Helv. Chim. Acta 1986, 69,
1699-1703.
(6) Oppolzer, W.; Blagg, J .; Rodriguez, I.; Walther, E. J . Am. Chem.
Soc. 1990, 112, 2767-2772.
(7) Mavropoulos, I.; Perlmutter, P. Tetrahedron Lett. 1996, 37,
3751-3754.
derivative 6b there was no evidence of conjugate addi-
tion,11 although dehydration of the initial adduct some-
times occurred to a small extent. We were able to obtain
crystals of the major diastereomeric product which were
suitable for X-ray crystallographic determination.24 The
solution is given in Figure 1 and clearly shows that the
major aldol product is, in fact, 11 and not 10 (the latter
(8) Bratt, K.; Garavelas, A.; Perlmutter, P.; Westman, G. J . Org.
Chem. 1996, 61, 2109-2117.
(9) Oppolzer, W.; Starkemann, C. Tetrahedron Lett. 1992, 33, 2439-
2442.
(10) Oppolzer, W.; Starkemann, C.; Rodrigues, I.; Bernardinelli, G.
Tetrahedron Lett. 1991, 32, 61-64.
(11) Oppolzer, W.; Lienard, P. Tetrahedron Lett. 1993, 34, 4321-
4324.
S0022-3263(96)01953-6 CCC: $14.00 © 1997 American Chemical Society

6398 J . Org. Chem., Vol. 62, No. 18, 1997
Notes
Ta ble 1. Resu lts for Ald ol Rea ction s of 13
entry
aldehyde (RCHO) R
productsa (14:15)
1
2
3
4
a , R ) vinyl
70:30
91:9
90:10
81:19
b, R ) ethyl
c, R ) isopropyl
d , R ) phenyl
a
Ratios were determined by analytical HPLC on a Porasil
column (eluant: ethyl acetate/hexane).
Sch em e 6
F igu r e 1. X-ray crystal structure of 11 (some hydrogens
omitted for clarity).
Sch em e 4
correlated. Thus, desilylation of 16 followed by catalytic
reduction gave material identical with the major propa-
nal aldol adduct (Scheme 6). For aldol reactions with
isobutyraldehyde (entry 3) and benzaldehyde (entry 4),
the stereochemistry of the major adduct in each case was
established by hydrolysis to the corresponding known
â-hydroxy acid14 and comparison of their optical rotations.
Asymmetric aldol reactions involving dialkylboron
enolate intermediates generally proceed through chair-
like transition states (i.e. 19, Figure 2). Were this the
case in the present study, then the major diastereomeric
products should have been 15a -d in reactions with
enolate 13. The finding that the major products were,
in fact, 14a -d suggests that a different transition state
is involved. We propose that a boatlike transition state
(i.e. 18, Figure 2) is responsible for the observed diaste-
reoselection. Similar transition states have been de-
scribed before15 and are thought to be important in aldol
reactions involving chiral enolates of methyl ketones.16-20
In this regard it may be more appropriate to consider
the enolates derived from N-acetylsultams as part of this
family of acetyl enolates (i.e. including N-acetyl and “C-
acetyl” derivatives).21 The torsional strain experienced
by 18 is, most likely, smaller than the unfavorable
pseudo-1,3-diaxial interaction (between one of the boron
ligands and the auxiliary) evident in 19. Preference for
the boat conformation 18, with “R” occupying the steri-
cally-less demanding pseudoequatorial position, leads to
Sch em e 5
would have been expected by analogy with aldol reactions
of the diethylboron enolates of N-propionylbornane-10,2-
sultams (see Scheme 2)). By comparison, reaction of the
lithium enolate of 5a gave an almost equal ratio of aldol
products.
As we required, for future work, the opposite stereo-
chemistry at the carbinol center to that obtained in 11,
we switched to the enantiomeric series (i.e. using enolate
13 derived from N-acetyl-2(S)-bornane-10,2-sultam 12
(Scheme 4). As expected, adduct 14a was the major
product. Purification of this aldol mixture was difficult
so it was converted into a mixture of the corresponding
TBDMS ethers from which the desired diastereomer 16
was easily obtained pure ([R]D 54.0, c 1.05, CHCl3) by
crystallization from ethanol.
Although the diastereoselectivity for each of these
aldols was not great (≈2.3:1 in favor of 11 or 14a ), we
were interested to establish whether this unexpected
diastereoselectivity was a more general phenomenon or
merely peculiar to reactions with acrolein. The results
for the aldol reactions of 13 with some typical aldehydes
(Scheme 5) are collected in Table 1. Consistent with our
results with acrolein, in each of the cases we examined,
the major adduct was 14 and not 15. In fact the
diastereoselectvity was found to be much better than that
for acrolein, ranging from 81:19 to 91:9.12,13
(12) The use of 1 equiv each of diethylboron triflate and diisopro-
pylethylamine gave identical stereoselection but with significant
quantities of unchanged starting material.
(13) In response to a referee’s suggestion we prepared purified
diethylboron triflate (see ref 15) and repeated several of the reactions
listed in Table 1. In all cases, the results were, within experimental
error, the same as those obtained using diethylboron triflate generated
“in situ”. This precludes the possibility of ethylboron ditriflate being
responsible for our results (see Boeckman, R. K., J r.; J ohnson, A. T.;
Musselman, R. A. Tetrahedron Lett. 1994, 35, 8521-8524).
(14) Helmchen, G.; Leikauf, U.; Taufer-Knopfel, I. Angew. Chem.,
Int. Ed. Engl. 1985, 24, 874-875.
(15) Evans, D. A.; Nelson, J . V.; Taber, T. R. J . Am. Chem. Soc. 1981,
103, 3099-3111.
(16) Gustin, D. J .; VanNieuwenhze, M. S.; Roush, W. R. Tetrahedron
Lett. 1995, 36, 3443-3446.-
(17) Bernardi, F.; Robb, M. A.; Suzzi-Valli, G.; Tagliavini, E.;
Trombini, C.; Umani-Ronchi, A. J . Org. Chem. 1991, 56, 6472-6475.
(18) Goodman, J . M.; Kahn, S. D.; Paterson, I. J . Org. Chem. 1990,
55, 3295-3303.
(19) Li, Y.; Paddon-Row, M. N.; Houk, K. N. J . Org. Chem. 1990,
55, 481-493.
(20) Bernardi, A.; Capelli, A. M.; Gennari, C.; Goodman, J . M.;
Paterson, I. J . Org. Chem. 1990, 55, 3576-3581.
(21) For examples of Lewis-acid promoted anti-aldol reactions which
would be expected to provide the opposite stereochemical result at the
newly-formed carbinol center to those described here see: Raimundo,
B. C.; Heathcock, C. H. Synlett 1995, 1213-1214 and references cited
therein.
The stereochemistry of the adducts from reactions of
13 with acrolein and propanal (entry 2) was chemically

Notes
J . Org. Chem., Vol. 62, No. 18, 1997 6399
F igu r e 2.
2H), 1.83-2.07 (m, 4H), 2.10-2.19 (m, 3H), 2.40 (s, 3H), 3.42
(d, J ) 13.8 Hz, 1H), 3.50 (d, J ) 13.8 Hz, 1H), 3.84 (dd, J )
7.7, 5.1 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 19.8, 20.7, 23.1,
26.3, 32.7, 38.3, 44.5, 47.6, 48.3, 52.7, 65.1, 168.5; HRMS calcd
for M+: m/z 257.109, found 257.108; MS m/z 257 (M+, 4%), 135
(59), 134 (100), 132 (43), 119 (38), 108 (48), 93 (45), 67 (35).
Gen er a l P r oced u r e for th e Ald ol Rea ction .6 To 1 M
triethylborane (3.2 mL, 3.2 mmol) in hexanes was added freshly
distilled triflic acid (290 µL, 3.2 mmol). After 30 min, the
homogeneous solution was cooled to -5 °C and the acetyl sultam
5a or 12 (412 mg, 1.6 mmol) in CH2Cl2 (6.5 mL) was added,
followed by diisopropylethyl amine (560 µL, 3.2 mmol) in CH2-
Cl2 (3.4 mL). The solution was stirred for a further 30 min after
which time it was cooled to -78 °C and a solution of the aldehyde
(2 equiv) in CH2Cl2 was added. The solution was stirred for an
additional 3 h and then quenched at -78 °C with pH 7 phosphate
buffer and allowed to warm to rt. The organic layer was
separated and the aqueous layer extracted with Et2O. The
combined extracts were washed with saturated aqueous NH4-
Cl, dried (MgSO4), and filtered, and the solvent was evaporated.
(2R)-N-[(3S)-3-Hyd r oxy-4-p en ten -1-oyl]bor n a n e-10,2-su l-
ta m (11). The general aldol procedure was followed using
N-acetyl sultam 5a (412 mg, 1.6 mmol) and acrolein (1.3 mL,
20 mmol) in CH2Cl2 (5 mL) which was added via a syringe pump
(0.2 mL/min), yielding a crude aldol mixture (326 mg, 65%):
HPLC (7:3), 8.93 (22), 10.46 (78). Flash chromatography (3:1,
petroleum ether/ethyl acetate) and crystallization from ethyl
acetate/petroleum ether yielded colorless prisms: mp 94-95 °C;
HPLC (7:3), 10.17; [R]20D -114.9 (c 0.92, CHCl3); IR (Nujol) 3539,
the correct diastereomeric product. Reactions of the R,â-
unsaturated aldehydes, acrolein and benzaldehyde, showed
poorer diastereoselectivity than the two saturated alde-
hydes. It is plausible that there may be a small electronic
preference for reaction via a chairlike transition state for
the former aldehydes the result of which would be a
reduction in diastereoselectivity.
In summary, we have demonstrated that diethylboron
enolates of N-acetylbornane sultams react with aldehydes
with good diastereoselectivity. Although this stereose-
lectivity is different to that observed in the reactions of
other, closely related chiral enolates it appears to be
reliable and predictable. It is proposed that the reaction
proceeds through a boatlike transition state. Conse-
quently this study has uncovered a useful, enantiomeri-
cally pure acetate synthon.
Exp er im en ta l Section
Gen er a l Meth od s. Toluene, CH2Cl2, and DMF were all dried
by distillation from CaH2. Benzaldehyde, propanal, acrolein, and
isobutyraldehyde were all freshly distilled prior to use. All
reactions were conducted under a nitrogen atmosphere.
Flash chromatography was carried out using SiO2 (230-400
mesh). HPLC analyses were performed using a SiO2 column
(3.9 mm × 300 mm) with both UV and refractive index detectors.
The eluant was hexanes/ethyl acetate mixtures and a flow rate
of 1 mL/min was used. Retention times are in minutes (area
%).
1
1690, 1319, 1136, 927 cm-1; H NMR (200 MHz, CDCl3) δ 0.97
(s, 3H), 1.16 (s, 3H), 1.35-1.50 (m, 2H), 1.80-2.00 (m, 3H), 2.05-
2.20 (m, 2H), 2.89 (dd, J ) 16.8, 7.9 Hz, 1H), 3.01 (dd, J ) 16.9,
4.2 Hz, 1H), 3.11 (d, J ) 5 Hz, 1H), 3.45 (d, J ) 17.7 Hz, 1H),
3.52 (d, J ) 17.7 Hz, 1H), 3.89 (dd, J ) 7.6, 5.2 Hz, 1H), 4.55-
4.70 (m, 1H), 5.16 (dt, J ) 10.4, 1.4 Hz, 1H), 5.33 (dt, J ) 17.2,
1.5 Hz, 1H), 5.90 (td, J ) 15.9, 10.5, 5.4 Hz, 1H); 13C NMR (50
MHz, CDCl3) δ 19.8, 20.8, 26.3, 32.7, 38.3, 42.0, 44.6, 47.7, 48.4,
52.8, 65.0, 68.8, 115.3, 138.5, 170.5; HRMS calcd for M+: m/z
313.135, found 313.135; MS m/z 313 (M+, 0.5%), 136 (64), 134
(91), 119 (64), 108 (90), 93 (77), 81 (100), 67 (45), 56 (71). Anal.
Calcd for C15H23NO4S: C, 57.5; H, 7.4; N, 4.5. Found: C, 57.8;
H, 7.7; N, 4.3.
(2S)-N-[(3R)-3-Hyd r oxy-4-p en ten -1-oyl]bor n a n e-10,2-su l-
ta m (14a ). The general aldol procedure was followed using
N-acetyl sultam 12 (412 mg, 1.6 mmol) and acrolein (1.3 mL,
20 mmol) in CH2Cl2 (5 mL) which was added via a syringe pump
(0.2 mL/min) to yield a crude aldol mixture (350 mg, 70%):
HPLC (4:1), 16.11 (30), 20.27 (70). Flash chromatography (3:1,
petroleum ether/ethyl acetate) and crystallization from ethyl
acetate/petroleum ether yielded colorless prisms: mp 95-96 °C;
HPLC (4:1), 20.16; [R]20D +112.6 (c 1.02, CHCl3); IR (Nujol) 3538,
1689, 1135, 927 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.98 (s, 3H),
1.16 (s, 3H), 1.31-1.59 (m, 2H), 1.84-1.98 (m, 3H), 2.03-2.20
(m, 2H), 2.91 (dd, J ) 8.1, 16.7 Hz, 1H), 3.01 (dd, J ) 3.8, 16.7
Hz, 1H), 3.11 (d, J ) 4.6 Hz, 1H), 3.44 (d, J ) 21.6 Hz, 1H), 3.52
(d, J ) 21.6 Hz, 1H), 3.89 (dd, J ) 5.1, 7.7 Hz, 1H), 4.56-4.62
(m, 1H), 5.15 (dt, J ) 1.3, 10.5 Hz, 1H), 5.33 (dt, J ) 1.3, 17.1
Hz, 1H), 5.89 (td, J ) 5.3, 10.5, 17.1 Hz, 1H); 13C NMR (50 MHz,
CDCl3) δ 19.7, 20.7, 26.2, 32.6, 38.2, 41.5, 44.5, 47.6, 48.4, 52.7,
Melting points were measured on a hot stage melting point
apparatus and are uncorrected. 1H NMR and 13C NMR spectra
were recorded at 200 MHz or 300 MHz and 50 MHz, respectively,
in either CDCl3 or d6-acetone.
(2S)-N-Acetylbor n a n e-10,2-su lta m (12).9 Toluene (150
mL) was added to (2S)-bornane-10,2-sultam22,23 (10 g, 46.5 mmol)
and NaH (2.1 g, 80% dispersion in mineral oil, 70 mmol) under
N2. This mixture was stirred at rt for 2 h after which time
freshly distilled acetyl chloride (5 mL, 70.3 mmol) in toluene (50
mL) was added slowly. Stirring was continued for a further 2
h, and the reaction was quenched with saturated aqueous NH4-
Cl (100 mL). After separation of the toluene layer, the aqueous
layer was extracted with ether (2 × 25 mL), the combined
organic extracts were dried (MgSO4) and filtered, and the solvent
removed to yield a white solid which was recrystallized from
ethyl acetate/petroleum ether to yield colorless crystals (9.8 g,
82%): mp 138-139°; HPLC (4:1), 7.58; [R]19 +104.8 (c 1.06,
D
CHCl3); IR (Nujol) 1687, 1425, 1324, 1140, 986 cm-1; H NMR
1
(300 MHz, CDCl3) δ 0.97 (s, 3H), 1.15 (s, 3H), 1.30-1.43 (m,
(22) Bartlett, P. D.; Knox, L. H. Organic Synthesis; J ohn Wiley and
Sons: New York, 1973; Collect. Vol. V; pp 196-198.
(23) Davis, F. A.; Towson, J . C.; Weismiller, M. C.; Lal, S.; Carroll,
P. J . J . Am. Chem. Soc. 1988, 110, 8477-8482.
(24) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.

6400 J . Org. Chem., Vol. 62, No. 18, 1997
Notes
64.9, 68.7, 115.2, 138.5, 170.4; MS m/z 313 (M+, 3%), 216 (20),
151 (81), 135 (82), 139 (68), 108 (70), 93 (65), 57 (100). Anal.
Calcd for C15H23NO4S: C, 57.5; H, 7.4; N, 4.5. Found: C, 57.3;
H, 7.2; N, 4.4.
CDCl3) δ 0.04 (s, 3H), 0.06 (s, 3H), 0.87 (s, 9H), 0.96 (s, 3H),
1.14 (s, 3H), 1.30-1.43 (m, 2H), 1.85-1.95 (m, 4H), 2.04-2.07
(m, 2H), 2.89 (dd, J ) 21.6, 6.4 Hz, 1H), 2.96 (dd, J ) 21.6, 6.6
Hz, 1H), 3.42 (d, J ) 13.8 Hz, 1H), 3.49 (d, J ) 13.8 Hz, 1H),
3.85 (t, J ) 6.3 Hz, 1H), 4.66 (q, J ) 6.6 Hz, 1H), 5.04 (dt, J )
10.5, 1.3 Hz, 1H), 5.20 (dt, J ) 17.1, 1.6 Hz, 1H), 5.80-5.92 (m,
1H); 13C NMR (50 MHz, CDCl3) δ -5.0, -4.4, 18.1, 19.9, 20.8,
25.8, 26.4, 32.8, 38.4, 44.2, 44.6, 47.7, 48.3, 53.0, 65.1, 70.8, 114.9,
140.2, 169.1; MS m/z 426 (M+, 3%), 370 (62), 314 (38), 172 (36),
155 (38), 138 (82), 107 (52), 93 (54), 75 (92), 73 (100), 59 (20).
Anal. Calcd for C21H37NO4SSi: C, 59.0; H, 8.7; N, 3.3. Found:
C, 59.2; H, 8.7; N, 3.4.
(2S)-N-[(3S)-3-H yd r oxyp en t a n -1-oyl]b or n a n e-10,2-su l-
ta m (14b). The general aldol procedure was followed using
N-acetyl sultam 12 (412 mg, 1.6 mmol) and propionaldehyde
(0.23 mL, 3.2 mmol) in CH2Cl2 (1 mL) to yield a crude aldol
mixture: HPLC (4:1), 15.66 (9), 19.93 (91). Flash chromatog-
raphy (3:1, petroleum ether/ethyl acetate) and crystallization
from ethyl acetate/petroleum ether yielded colorless crystals (436
mg, 86%): mp 73 °C; HPLC (4:1), 20.29; [R]20 +125.8 (c 1.00,
D
CHCl3); IR (Nujol) 3412, 1660, 1337, 1140, 978 cm-1; H NMR
(3R)-3-Hyd r oxy-4-m eth ylp en ta n oic Acid .6,9 To 14c (95
mg, 0.28 mmol) in THF/H2O (4:1, 4 mL) at 0 °C was added
LiOH‚H2O (17 mg, 0.40 mmol) and 30 wt % H2O2 (0.155 mL,
1.52 mmol). This was stirred at 0 °C for 3 h and then quenched
with saturated Na2SO3 (1 mL). Concentrated NH3 (1 mL) was
added and the solution extracted with CH2Cl2 to yield after
separation, drying (MgSO4), and evaporation the sultam (60 mg,
100%). The aqueous layer was acidified with concd HCl and
extracted with ether (3 × 10 mL). The combined organic extracts
were dried (MgSO4), and the solvent was removed to yield a
1
(300 MHz, CDCl3) δ 0.94 (t, J ) 7.4 Hz, 3H), 0.95 (s, 3H), 1.13
(s, 3H), 1.29-1.46 (m, 2H), 1.47-1.59 (m, 2H), 1.86-2.02 (m,
3H), 2.03-2.18 (m, 2H), 2.74 (dd, J ) 16.7, 8.9 Hz, 1H), 2.90
(dd, J ) 16.7, 2.7 Hz, 1H), 3.40 (bs, 1H), 3.42 (d, J ) 13.8 Hz,
1H), 3.49 (d, J ) 13.8 Hz, 1H), 3.85 (dd, J ) 7.6, 5 Hz, 1H),
3.92-4.01 (m, 1H); 13C NMR (50 MHz, CDCl3) δ 9.7, 19.7, 20.7,
26.2, 29.2, 32.6, 38.3, 41.6, 44.5, 47.6, 48.3, 52.7, 64.9, 69.2, 171.0;
MS m/z 315 (M+, 0.1%), 286 (10), 216 (25), 151 (58), 135 (61),
134 (78), 119 (41), 108 (63), 93 (71), 83 (100), 79 (47), 67 (59), 59
(75), 55 (88). Anal. Calcd for C15H25NO4S: C, 57.12; H, 7.99; N,
4.44. Found: C, 57.08; H, 8.03; N, 4.32.
colorless oil (26 mg, 65%): [R]20 +40.0 (c 1.32, CHCl3) [lit.13
D
1
[R]25 +40.2 (c 1.2, CHCl3)]; H NMR (200 MHz, CDCl3) δ 0.91
D
(2S)-N-[(3R)-3-Hyd r oxy-4-m eth ylp en ta n -1-oyl]bor n a n e-
10,2-su lta m (14c). The general aldol procedure was followed
using N-acetyl sultam 12 (412 mg, 1.6 mmol) and isobutyral-
dehyde (0.29 mL, 3.2 mmol) in CH2Cl2 (1 mL) to yield a crude
aldol mixture: HPLC (4:1), 11.72 (10), 15.33 (90). Flash
chromatography (3:1, petroleum ether/ethyl acetate) and crystal-
lization from ethyl acetate/petroleum ether yielded fine needles
(419 mg, 76%): mp 109-110 °C; HPLC (4:1), 15.45; [R]20D +118.6
(c 1.04, CHCl3); IR (Nujol) 3558, 1674, 1327, 1134 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.92-0.98 (m, 9H), 1.16 (s, 3H), 1.45-1.35
(m, 2H), 1.74 (oct, J ) 6.6 Hz, 1H), 1.88-1.98 (m, 3H), 2.03-
2.19 (m, 2H), 2.76 (dd, J ) 16.5, 9.5 Hz, 1H), 2.93 (dd, J ) 16.6,
2.6 Hz, 1H), 2.98 (d, J ) 4.1 Hz, 1H), 3.45 (d, J ) 13.9 Hz, 1H),
3.52 (d, J ) 13.8 Hz, 1H), 3.79-3.91 (m, 2H); 13C NMR (50 MHz,
CDCl3) δ 17.6, 18.4, 19.8, 20.8, 26.4, 32.8, 33.2, 38.4, 39.5, 44.6,
47.7, 48.4, 52.9, 65.1, 72.8, 172.0; HRMS calcd for M+ - 18
(H2O): m/z 311.156, found 311.155; MS m/z 311 (M+ - H2O,
4.5%), 286 (39), 216 (69), 151 (69), 135 (100), 134 (73), 108 (71),
93 (86), 91 (50), 79 (57), 73 (89), 69 (68), 55 (79).
(d, J ) 5.1 Hz, 3H), 0.94 (d, J ) 5.4 Hz, 3H), 1.72 (s, J ) 6.6 Hz,
1H), 2.43 (dd, J ) 16.2, 9.8 Hz, 1H), 2.55 (dd, J ) 16.3, 3.5 Hz,
1H), 3.72-3.94 (m, 1H).
(3R)-3-Hyd r oxy-3-p h en ylp r op a n oic Acid .6,9 To 14d (162
mg, 0.45 mmol) in THF/H2O (4:1, 8 mL) at 0 °C was added
LiOH‚H2O (25 mg, 0.60 mmol) and 30 wt % H2O2 (0.250 mL,
2.44 mmol). This was stirred at 0 °C for 3 h and then quenched
with saturated Na2SO3 (1 mL). Concentrated NH3 (1 mL) was
added and the solution extracted with CH2Cl2 to yield after
separation, drying (MgSO4), and evaporation the sultam (92 mg,
96%). The aqueous layer was acidified with concd HCl and
extracted with ether (3 × 10 mL). The combined organic extracts
were dried (MgSO4), and the solvent was removed to yield a
white solid (70 mg, 94%): mp 119-121 °C; [R]20 +17.2 (c 2.32,
D
95% EtOH) [lit.13 [R]25D +17.9 (c 2.5, 95% EtOH)]; 1H NMR (200
MHz, d6-acetone) δ 2.69 (d, J ) 6.6 Hz, 2H), 5.15 (t, J ) 6.7 Hz,
1H), 7.21-7.43 (m, 5H).
Con ver sion of 16 to 14b. The silyl ether 16 (89 mg, 0.21
mmol) was stirred in a THF:concd HCl (5.5 mL, 10:1) solution
at rt for 3 h after which it was diluted with water (10 mL) and
extracted with ether (1 × 10 mL, 2 × 5 mL). The combined
extracts were dried (MgSO4) and filtered, and the solvent was
(2S)-N-[(3R)-3-Hyd r oxy-3-p h en ylp r op a n -1-oyl]bor n a n e-
10,2-su lta m (14d ). The general aldol procedure was followed
using N-acetyl sultam 12 (412 mg, 1.6 mmol) and benzaldehyde
(0.32 mL, 3.2 mmol) in CH2Cl2 (1 mL) to yield a crude aldol
mixture: HPLC (4:1), 15.78 (19), 20.66 (81). Flash chromatog-
raphy (3:1, petroleum ether/ethyl acetate) and crystallization
from ethyl acetate/petroleum ether yielded colorless crystals (433
1
evaporated to yield 14b (60 mg, 92%) whose H NMR spectrum
was identical to that of the purified acrolein aldol adduct
previously obtained in this work and was used without purifica-
tion. The deprotected product was dissolved in absolute ethanol
(1 mL), and a catalytic amount of 10% Pd/C was added. The
mixture was stirred under an atmosphere of H2 for 15 min after
which time the mixture was filtered through a Celite pad and
the solvent removed in vacuo to yield 14b (49 mg, 81%) whose
1H NMR spectrum was identical to a sample previously obtained
in this work. HPLC (4:1), 19.57. Similar processing of a 1:1
diastereomeric of 16 and 17 yielded a 1:1 mixture of 14b and
15b. HPLC (4:1), 15.14, 19.77.
mg, 75%): mp 167-168 °C; HPLC (4:1), 20.18; [R]20 +116.5 (c
D
1
1.05, EtOH); IR (Nujol) 3509, 1679, 1331, 1139 cm-1; H NMR
(300 MHz, CDCl3) δ 0.96 (s, 3H), 1.11 (s, 3H), 1.34-1.44 (m,
2H), 1.87-1.97 (m, 3H), 2.03-2.17 (m, 3H), 3.05-3.20 (m, 2H),
3.40-3.52 (m, 3H), 3.86-3.90 (m, 1H), 5.16-5.22 (m, 1H), 7.24-
7.40 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 19.7, 20.7, 26.3, 32.7,
38.3, 44.1, 44.5, 47.6, 48.4, 52.7, 65.0, 70.2, 125.7, 127.6, 128.4,
142.1, 170.7; HRMS calcd for MH+ - 18 (H2O): m/z 346.148,
found 346.147; MS m/z 364 (MH+, 1%), 346 (MH+ - H2O, 77%),
258 (51), 216 (50), 151 (37), 136 (47), 135 (100), 109 (68), 105
(73), 93 (37).
Ack n ow led gm en t. S.B. is grateful to the Australian
Government for an Australian Postgraduate Research
Award, and P.P. is grateful to the Australian Research
Council for financial support. We thank Dr. G. D.
Fallon for determining the X-ray crystal structure of 11.
(2S)-N-[(3R)-3-[(ter t-Bu tyld im eth ylsilyl)oxy]-4-p eten -1-
oyl]bor n a n e-10,2-su lta m (16). To the crude acrolein aldol
mixture (1.3 g), obtained from the reaction of N-acetyl sultam
12 and acrolein, were added imidazole (720 mg, 10.6 mmol),
DMAP (6 mg, 0.05 mmol), and tert-butyldimethylsilyl chloride
(700 mg, 4.7 mmol) in DMF (4 mL) and stirred at 45 °C under
N2 for 16 h. The reaction was quenched with H2O (10 mL),
extracted with CH2Cl2 (3 × 5 mL), and dried (MgSO4). The
majority of the solvent was removed in vacuo with the residual
DMF being removed with the aid of a freeze dry apparatus to
yield a solid from which 16 could be crystallized from absolute
EtOH to yield fine needles (405 mg, 23% over two steps de pure,
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra for
compounds 12, 14c, and 14d have been provided in lieu of
combustion analysis (3 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
nonoptimized): mp 126-127 °C; [R]20 +54.0 (c 1.05, CHCl3);
D
IR (Nujol) 1674, 1335, 1139, 992 cm-1
;
1H NMR (300 MHz,
J O961953B