Diastereoselective synthesis of useful building blocks by crotylation of β-branched α-methylaldehydes with potassium crotyltrifluoroborates

Article abstract of DOI:10.1021/jo801106b

(Chemical Equation Presented) The diastereoselective construction of stereotriads having consecutive methyl, hydroxy, and methyl substituents was realized by the substrate-controlled crotylation of β-branched α-methylaldehydes with potassium crotyltrifluoroborates. Especially, crotylation of 2-(1,3-dithian-2-yl)propanal with potassium (E)- crotyltrifluoroborate afforded, in good yield and with excellent diastereoselectivity, a useful building block that has different and potential functional groups on both ends.

Full text of DOI:10.1021/jo801106b

Diastereoselective Synthesis of Useful Building Blocks by Crotylation
of ꢀ-Branched r-Methylaldehydes with Potassium
Crotyltrifluoroborates
Kyosuke Tanaka, Yukiko Fujimori, Yoko Saikawa,* and Masaya Nakata*
Department of Applied Chemistry, Faculty of Science and Technology, Keio UniVersity, 3-14-1 Hiyoshi,
Kohoku-ku, Yokohama 223-8522, Japan
saikawa@applc.keio.ac.jp; msynktxa@applc.keio.ac.jp
ReceiVed May 22, 2008
The diastereoselective construction of stereotriads having consecutive methyl, hydroxy, and methyl
substituents was realized by the substrate-controlled crotylation of ꢀ-branched R-methylaldehydes with
potassium crotyltrifluoroborates. Especially, crotylation of 2-(1,3-dithian-2-yl)propanal with potassium
(E)-crotyltrifluoroborate afforded, in good yield and with excellent diastereoselectivity, a useful building
block that has different and potential functional groups on both ends.
SCHEME 1. Addition of Potassium Crotyltrifluoroborates
to r-Methylaldehydes
Introduction
Stereotriads characterized by their consecutive methyl, hy-
droxy, and methyl substituents are important building blocks
for the synthesis of natural products such as macrolides and
polyethers. Aldol reactions between enolates derived from ethyl
ketones and R-methylaldehydes are a conventional method for
constructing such stereotriads. The reactions of crotylmetal
reagents with R-methylaldehydes are an important alternative
to aldol reactions and have been successfully used for the same
purpose.1 Recently, Batey et al. reported a new class of
crotylboron compounds, potassium crotyltrifluoroborates, and
their addition to aldehydes.2 Potassium organotrifluoroborates
have become versatile organometallic reagents for carbon-carbon
bond formation because of their air and moisture stable
properties and thereby easy handling.3,4 Among them, potassium
alkenyl- and aryltrifluoroborates are widely employed for
coupling reactions such as the Suzuki-Miyaura coupling.4,5 On
the other hand, there have been few reports concerning allylation
and crotylation of aldehydes by allyl- and crotyltrifluoroborates.2
Encouraged by Batey’s diastereoselective crotylation of R- and
ꢀ-silyloxy-substituted aldehydes,2b,d we anticipated that croty-
lation of R-methylaldehydes with potassium crotyltrifluorobo-
rates would be a good method for the diastereoselective synthesis
of the aforementioned stereotriads (Scheme 1).6 We now report
that 2-(1,3-dithian-2-yl)propanal is an excellent substrate and
both ends of the resulting coupling product are available for
further elaboration.
(1) For reviews, see: (a) Roush, W. R. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Heathcock, C. H. Eds.; Pergamon: Oxford, UK, 1991;
Vol. 2, pp 1-53. (b) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207–
2293. (c) Kennedy, J. W. J.; Hall, D. G. Angew. Chem., Int. Ed. 2003, 42, 4732–
4739. (d) Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763–2793. (e) Hall,
D. G. Synlett 2007, 1644–1655.
(4) For recent reviews on organotrifluoroborates, see: (a) Darses, S.; Genet,
J.-P. Eur. J. Org. Chem. 2003, 4313–4327. (b) Molander, G. A.; Figueroa, R.
Aldrichim. Acta 2005, 38, 49–56. (c) Molander, G. A.; Ellis, N. Acc. Chem.
Res. 2007, 40, 275–286. (d) Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron
2007, 63, 3623–3658. (e) Darses, S.; Genet, J.-P. Chem. ReV. 2008, 108, 288–
325.
(2) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Tetrahedron Lett. 1999,
40, 4289–4292. (b) Batey, R. A.; Thadani, A. N.; Smil, D. V.; Lough, A. J.
Synthesis 2000, 990–998. (c) Thadani, A. N.; Batey, R. A. Org. Lett. 2002, 4,
3827–3830. (d) Thadani, A. N.; Batey, R. A. Tetrahedron Lett. 2003, 44, 8051–
8055.
(5) (a) Darses, S.; Genet, J.-P. Tetrahedron Lett. 1997, 38, 4393–4396. (b)
Batey, R. A.; Quach, T. D. Tetrahedron Lett. 2001, 42, 9099–9103. (c) Molander,
G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302–4314, and references cited
therein.
(6) Synthesis of a stereotriad having the identical vinyl ends, using the
coupling of vinyloxiranes and potassium crotyltrifluoroborates, has been reported.
See: Lautens, M., Ouellet, S. G., Raeppel, S. Angew. Chem., Int. Ed. 2000, 39,
4079-4082.
(3) (a) Chambers, R. D.; Clark, H. C.; Willis, C. J. J. Am. Chem. Soc. 1960,
82, 5298–5301. (b) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf,
M. R. J. Org. Chem. 1995, 60, 3020–3027.
6292 J. Org. Chem. 2008, 73, 6292–6298
10.1021/jo801106b CCC: $40.75 2008 American Chemical Society
Published on Web 07/16/2008

DiastereoselectiVe Crotylation with K Crotyltrifluoroborates
TABLE 1. Crotylation of ꢀ-Alkoxy-r-methylaldehydes 1 with
Potassium Crotyltrifluoroborates 2
TABLE 2. Crotylation of ꢀ-Branched r-Methylaldehydes 7 with
Potassium Crotyltrifluoroborates 2
entry
substratea (R)
borate
time (h)
% yieldb (ratio)c
1
2
3
4
5
6
7
8
1a (PMB)
1b (TBS)
1c (Tr)
1d (TBDPS)
1a (PMB)
1b (TBS)
1c (Tr)
2a
2a
2a
2a
2b
2b
2b
2b
1
1
1
0.5
1
1
1
0.5
87 (3a:4a ) 2:1)
77 (3b:4b ) 2:1)
95 (3c:4c ) 2.5:1)
98 (3d:4d ) 3:1)
99d (5a:6a ) 1.5:1)
69d (5b:6b ) 2:1)
97d (5c:6c ) 1.5:1)
91d (5d:6d ) 2:1)
1d (TBDPS)
a Aldehydes
1
were racemates. b Combined yield of the barely
separable adducts after silica gel column chromatography. c The ratio
was determined by H NMR analysis of the adducts. d Trace amounts of
1
3 and 4 also present in the adducts.
Results and Discussion
We first examined the crotylation of the racemic ꢀ-alkoxy-
R-methylaldehydes (1, R ) PMB, TBS, Tr, and TBDPS)7 with
potassium(E)-crotyltrifluoroborate(2a)underBatey’sconditions2c,d
using a 0.1 molar amount of tetrabutylammonium iodide (TBAI)
as a catalyst in 1:1 CH2Cl2-H2O at rt. The results are shown
in Table 1. For each reaction, the yield was satisfactory;
however, the diastereoselectivity was modest (entries 1-4).8
We next examined the crotylation of 1 with potassium (Z)-
crotyltrifluoroborate (2b) (entries 5-8). The yield was also
satisfactory, but the diastereoselectivity was worse than that in
the E-case.
These results implied that, at least in the E-case, the bulkiness
at the aldehyde ꢀ-position somewhat affects the diastereose-
lectivity. Therefore, we next chose ꢀ-branched R-methylalde-
hydes as the substrates (Table 2).9 The result of the crotylation
of 2-(1,3-dioxan-2-yl)propanal 7a9a with 2a (entry 1) was what
we had expected: 8a:9a ) 11:1.10 In 1982, Kishi et al. reported
that the CrCl2-mediated crotylation of 7a afforded 8a and 9a
with the same selectivity as our case.11 Gratifingly, we found
that the crotylation of 2-(1,3-dithian-2-yl)propanal (7b)9b with
2a gave 8b in high yield with excellent selectivity (8b:9b )
24:1, entry 2).10 Furthermore, we attempted crotylation of
a Aldehydes
7
were racemates. b Combined yield of the barely
separable adducts after silica gel column chromatography. c The ratio
was determined by 1H NMR analysis of the adducts. d 7c and 7c′ are
diastereomers. e Trace amounts of 8 and 9 also present in the adducts.
aldehydes 7c9c and its diastereomer 7c′ 9c with 2a and obtained
8c and 8c′ 10 as a single isomer, respectively (entries 3 and 4).
In contrast to the favorable E-case, crotylation of 7a and 7b
with 2b gave the adducts with miserable diastereoselectivity
(10a:11a ) 1.1:1 and 10b:11b ) 2:1, entries 5 and 6). Only
the crotylation of 7c and 7c′ with 2b displayed higher levels of
diastereoselectivity (10c:11c ) 8:1 and 10c′:11c′ ) 10:1
depending on the diastereomers used, entries 7 and 8).
Addition of potassium crotyltrifluoroborates to aldehydes is
believed to involve the six-membered transition states.2d Our
first results (Table 1) obtained for the crotylation of ꢀ-alkoxy-
R-methylaldehydes 1 with 2 were consistent with those of the
previous report with pinacol crotylboronates.8a We consider the
mechanistic origin of the observed diastereoselectivity for the
(7) Aldehydes 1 were prepared from 2-methyl-1,3-propanediol in two steps.
For 1b see: (a) Kiyooka, S.; Shahid, K. A.; Goto, F.; Okazaki, M.; Shuto, Y. J.
Org. Chem. 2003, 68, 7967–7978. For 1d see: (b) Kiyooka, S. Tetrahedron:
Asymmetry 2003, 14, 2897–2910. 1a and 1c were similarly prepared.
(8) Stereochemical assignments of 3b-6b, 3c, and 3d-6d were based on
1H NMR comparisons with the reported data. For 3b-6b and 3d-6d see: (a)
Roush, W. R.; Palkowitz, A. D.; Ando, K. J. Am. Chem. Soc. 1990, 112, 6348–
6359. For 3c see: (b) Morita, A.; Kuwahara, S. Tetrahedron Lett. 2007, 48, 3163–
3166. Stereochemical assignments of 3a-6a and 4c-6c were based on the
similarities of their 1H NMR spectra with 3d-6d and mechanistic considerations.
(9) 7a was prepared from methacrolein and 2,2-dimethyl-1,3-propanediol
according to the reported procedure. See: (a) Kelly, T. R.; Fu, Y.; Xie, R. L.
Tetrahedron Lett. 1999, 40, 1857–1860. For (-)-7b see: (b) Smith, A. B., III;
Adams, C. M.; Barbosa, S. A. L.; Degnan, A. P. Proc. Nat. Acc. Sci. 2004, 101,
12042–12047. Racemate 7b was prepared from 1d according to the same
procedure. (c) For preparation of 7c and 7c′, see the Supporting Information.
(10) Structure determination of the adducts, see the Supporting Information.
(11) Lewis, M. D.; Kishi, Y. Tetrahedron Lett. 1982, 23, 2343–2346.
(12) The ꢀ-substituent effects on the aldehyde π-facial selectivity are
suggested in the previous reports, see: (a) Hoffmann, R. W.; Weidmann, U.
Chem. Ber. 1985, 118, 3966–3979. (b) Hoffmann, R. W.; Brinkmann, H.;
Frenking, G. Chem. Ber. 1990, 123, 2387–2394. (c) Evans, D. A.; Dart, M. J.;
Duffy, J. L.; Yang, M. G. J. Am. Chem. Soc. 1996, 118, 4322–4343. See also: (d)
Still, W. C.; Schneider, J. A. Tetrahedron Lett. 1980, 21, 1035–1038.
J. Org. Chem. Vol. 73, No. 16, 2008 6293

Tanaka et al.
SCHEME 2. Removal of Dithioacetal in 12
the disfavored conformation at the ꢀ-position (corresponding
to c). The competition of these steric and electronic repulsions
can explain the less pronounced diastereoselectivity for the
crotylation of the Z-case. Similarly, the observation on the
crotylation of 7a can be rationalized by considering these
ꢀ-substituent effects. The origin of the different level of
diastereoselectivity between 7a and 7b is probably due to the
size of the ꢀ-substituent (dioxane vs dithiane). In the case of
the fully ꢀ-substituted aldehydes 7c and 7c′, the steric effect of
the conformation at the ꢀ-position would be canceled, and the
bulkiness at the R-position must be responsible for improvement
of diastereoselectivity.13
The usefulness of thus-obtained 8b as a building block for
natural product syntheses was next demonstrated. Prior to this,
we confirmed the utility of 8b as a chiral building block. Thus,
an attempt was made to crotylate the chiral aldehyde (-)-7b,9b
which was prepared from commercially available methyl (S)-
3-hydroxy-2-methylpropionate (Roche ester) in six steps9b or
prepared by oxidation of the corresponding alcohol derived from
Roche ester in three steps.14 The crotylation of (-)-7b with 2a
afforded the optically pure 8b without racemization. The
following demonstrations were thus carried out by using the
racemic 8b (Schemes 2–4). After silylation of 8b with TBSOTf
and N,N-diisopropylethylamine (DIPEA) in CH2Cl2, the result-
ing TBS ether 12 was subjected to dedithioacetalization condi-
tions (Scheme 2). Although both the starting material 12 and
the product 13 were found to be unstable under several
deprotection conditions (e.g., MeI,15 PhI(CO2CF3)2,16 NBS,17
and DMP18), we found that MeI15 and NBS17 were the reagents
of choice, giving the desired aldehyde 1319 in 57% and 54%
yields, respectively.
An alternative sequence suggests the possibility of using 8b
for conversion from the opposite side (Scheme 3). Oxidative
cleavage of the terminal alkene by ozonolysis20 afforded
aldehyde 14 whose dithiane portion was also oxidized to the
mono-oxide (7:3 mixture of diastereomers). Even when ozo-
nolysis of 12 was carried out for 1 h, no overoxidized products
were obtained. The resulting dithiane mono-oxide was stable
for further conversion. Aldehyde 14 was reduced to the alcohol,
which was protected as the TBDPS ether. Dedithioacetalization
FIGURE 1. Plausible transition state geometries of crotylation of 7b
with 2.
crotylation of aldehyde 7b as a representative, based on the
previously reported hypotheses concerning crotylation8a,12a,b and
aldol reactions.12c,13 It is reasonable to presume that avoidance
of a serious gauche-gauche pentane interaction is a dominant
rule.12a,b,13 Despite the favorable transition states (Figure 1, A
and B), which satisfy this assumption, the resulting diastereo-
selectivities are quite different in the E- and Z-cases. In general,
in spite of the anti-Felkin transition state (i.e., B in Figure 1),
excellent diastereoselectivity is often observed when aldehydes
have a sufficiently large R-substituent in addition to the R-methyl
group.13 Therefore, to account for the difference in our case,
the conformation of the ꢀ-position must be considered.11 Among
three aldehyde conformations (Figure 1, a-c), conformation a
is the most favorable based on sterics. For the crotylation of
the E-case, the transition structure A is ideal including the
ꢀ-substituent effects (corresponding to a). For the crotylation
of the Z-case, the favored conformation at the ꢀ-position
produces a severe electronic repulsion between the lone pairs
of the sulfur and oxygen atoms (B1), which was previously
recognized as a destabilizing dipolar interaction.12c Another
transition structure B2 without such an electronic repulsion
suffers from the disfavored conformation at the ꢀ-position
(corresponding to c). Transition structure C, which avoids
placing the sulfur atom in the Ha position,12b also suffers from
(14) (a) Ide, M.; Nakata, M. Bull. Chem. Soc. Jpn. 1999, 72, 2491–2499.
(b) Ide, M.; Yasuda, M.; Nakata, M. Synlett 1998, 936–938.
(15) (a) Jin, M.; Taylor, R. E. Org. Lett. 2005, 7, 1303–1305. (b) Fetizon,
M.; Jurion, M. J. Chem. Soc., Chem. Commun. 1972, 382–383. (c) Colombo,
L.; Gennari, C.; Scolastico, C.; Beretta, M. G. J. Chem. Soc., Perkin Trans. 1
1978, 1036–1041.
(16) Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 287–290.
(17) (a) Corey, E. J.; Erickson, B. W. J. Org. Chem. 1971, 36, 3553–3560.
(b) Shmidt, U.; Meyer, R.; Leitenberger, V.; Griesser, H.; Lieberknecht, A.
Synthesis 1992, 1025–1030.
(18) Langille, N. F.; Dakin, L. A.; Panek, J. S. Org. Lett. 2003, 5, 575–578.
(19) M´ınguez, J. M.; Kim, S.-Y.; Giuliano, K. A.; Balachadran, R.; Madiraju,
C.; Day, B. W.; Curran, D. P. Bioorg. Med. Chem. 2003, 11, 3335–3357. The
1
reported H NMR spectral datum was not identical with 13 for some unknown
reason. Aldehyde 13 was then reduced (NaBH4, MeOH) and the resulting alcohol
was identified on the basis of the spectral data reported in the same paper. See
the Supporting Information.
(13) Roush, W. R. J. Org. Chem. 1991, 56, 4151–4157, and references cited
therein.
(20) Anaya, J.; Gero, S. D.; Grande, M.; Hernando, J. I. M.; Laso, N. M.
Bioorg. Med. Chem. 1999, 7, 837–850.
6294 J. Org. Chem. Vol. 73, No. 16, 2008

DiastereoselectiVe Crotylation with K Crotyltrifluoroborates
SCHEME 3. Oxidative Cleavage of 12 and Subsequent
Conversion
Conclusions
In summary, the crotylation of 2-dithianylaldehydes 7b, 7c,
and 7c′ with air- and moisture-stable potassium (E)-crotyltrif-
luoroborate was readily realized in good yield and with excellent
diastereoselectivity. In addition, the usefulness of the coupling
product 8b as a building block aiming at a further elaboration
was demonstrated. The results presented in this article would
broaden the synthetic usefulness of organotrifluoroborate chem-
istry. Application of 8b for natural product syntheses is now
underway in our laboratories.
Experimental Section
General Procedure for Crotylation of Aldehydes with Potas-
sium Crotyltrifluoroborates. To a stirred solution of aldehyde (1.0
equiv) in 1:1 CH2Cl2-H2O (0.17 M) were added at rt tetra-n-
butylammonium iodide (0.10 molar amount) and potassium cro-
tyltrifluoroborate (1.2 equiv). After the reaction time indicated in
Tables 1 and 2, saturated aqueous NaHCO3 was added and the
mixture was extracted with CHCl3. The extracts were washed with
saturated aqueous NaCl, dried over Na2SO4, and concentrated. The
residue was purified by column chromatography on silica gel to
afford a mixture of diastereomers of homoallylalcohols as a
colorless syrup.
SCHEME 4. Lithiation and Addition Reaction of 8b
Homoallylalcohol 8a11 from 7a and 2a. Rf 0.49 (toluene/EtOAc
1
) 10:1); H NMR (300 MHz, CDCl3, TMS ) 0.00) δ 0.72 (s,
3H), 0.95 (d, J ) 6.6 Hz, 3H), 0.99 (d, J ) 6.6 Hz, 3H), 1.19 (s,
3H), 1.92 (ddq, J ) 7.8, 3.8, 1.8 Hz, 1H), 2.28 (m, 1H), 2.82 (d,
J ) 1.5 Hz, 1H), 3.42 (d, J ) 10.0 Hz, 1H), 3.45 (d, J ) 10.0 Hz,
1H), 3.64 (d, J ) 10.0 Hz, 2H), 3.74 (br d, J ) 9.3 Hz, 1H), 4.48
(d, J ) 3.9 Hz, 1H), 5.06 (ddd, J ) 9.9, 2.0, 0.8 Hz, 1H), 5.10 (br
d, J ) 17.6 Hz, 1H), 5.86 (ddd, J ) 17.6, 9.9, 7.8 Hz, 1H); 13C
NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ 7.1, 16.6, 21.7, 22.9,
30.2, 38.7, 41.3, 73.8, 77.1, 77.3, 105.0, 114.6, 142.2; IR (neat,
cm-1) 3520, 3080, 2958, 2850, 1640, 1465, 1397, 1310, 1238, 1208,
1160, 1108, 1040, 1018, 995, 963, 922, 790, 758; LRMS (EI) m/z
(M+) 228.1; HRMS (EI) m/z (M+) calcd for C13H24O3 228.1726,
found 228.1747.
of the resulting 15 was performed with NBS17a,21 in the presence
of NaHCO3 to give aldehyde 1622 in good yield (Scheme 3).
Homoallylalcohol 8b from 7b and 2a. Rf 0.46 (toluene/EtOAc
) 10:1); 1H NMR (300 MHz, CDCl3, TMS ) 0.00) δ 0.98 (d, J )
6.6 Hz, 3H), 1.12 (d, J ) 6.8 Hz, 3H), 1.79-1.94 (m, 1H), 1.89
(d, J ) 3.6 Hz, 1H), 2.01 (m, 1H), 2.08-2.19 (m, 1H), 2.32 (m,
1H), 2.81-2.98 (m, 4H), 3.71 (ddd, J ) 8.2, 3.6, 3.6 Hz, 1H),
4.20 (d, J ) 7.8 Hz, 1H), 5.13 (dd, J ) 10.0, 1.8, 1H), 5.14 (ddd,
A special characteristic of the 1,3-dithianes is the utility of
their carbanions in coupling reactions for natural product
syntheses.23 Smith et al. suggested that δ-alkenyldithianes resist
lithiation due to through-space donation of electrons from the
olefin π orbital to the C-S σ* orbital.24 Similar to Smith’s
results, lithiation of 12 with BuLi gave no 12D after deuteration
(Scheme 4). In contrast, it was found that the nonprotected 8b
was readily lithiated to give 8bD after the addition of D2O. The
above anion was successfully coupled with aldehyde 1725 to
give a 2:1 mixture of 18 in 66% yield. After silylation of 18,
the resulting 19 was subjected to dedithioacetalization, using
PhI(CO2CF3)216 followed by ozonolysis to give aldehyde 20 in
good yield.
J ) 17.4, 1.8, 1.2, 1H), 5.78 (ddd, J ) 17.4, 10.0, 8.2 Hz, 1H); 13
C
NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ 10.5, 16.5, 26.1, 30.6,
30.8, 39.7, 41.9, 52.8, 74.1, 116.3, 141.1; IR (neat, cm-1) 3470,
3078, 2970, 2930, 2900, 1640, 1458, 1420, 1380, 1320, 1278, 1250,
1190, 1092, 1001, 980, 915, 760; LRMS (EI) m/z (M+) 232.1;
HRMS (EI) m/z (M+) calcd for C11H20OS2 232.0956, found
232.0949. (-)-8b: [R]29.5 -11 (c 0.35, CHCl3)
D
Homoallylalcohol 8c from 7c and 2a. Rf 0.51 (toluene/EtOAc
) 10:1); 1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 0.95 (d, J
) 7.0 Hz, 3H), 1.07 (s, 9H), 1.24 (d, J ) 7.0 Hz, 3H), 1.71-1.91
(m, 2H), 1.96-2.09 (m, 2H), 2.05 (s, 3H), 2.20 (d, J ) 2.8 Hz,
1H), 2.27 (m, 1H), 2.45-2.64 (m, 3H), 3.04-3.28 (m, 2H), 3.63
(ddd, J ) 10.2, 10.2, 4.8 Hz, 1H), 3.71 (ddd, J ) 10.2, 6.8, 3.4
Hz, 1H), 4.13 (dd, J ) 9.0, 2.8 Hz, 1H), 5.05 (dd, J ) 9.8, 1.6 Hz,
1H), 5.09 (br d, J ) 17.2 Hz, 1H), 5.86 (ddd, J ) 17.2, 9.8, 8.0
Hz, 1H), 5.93 (d, J ) 9.8 Hz, 1H), 7.35-7.47 (m, 6H), 7.66-7.72
(m, 4H); 13C NMR (75 MHz, CDCl3 CDCl3 ) 77.00) δ 9.1, 16.9,
19.1, 21.1, 24.2, 26.2, 26.7, 26.8, 33.3, 41.3, 41.8, 60.6, 60.9, 72.0,
74.8, 114.4, 127.6, 129.6, 129.6, 133.4, 133.6, 135.5, 135.7, 142.2,
170.1; IR (neat, cm-1) 3562, 3073, 2960, 2930, 2860, 1743, 1640,
1590, 1472, 1462, 1428, 1372, 1280, 1232, 1112, 1018, 963, 910,
822, 768, 700; LRMS (EI) m/z (M+) 586.2; HRMS (EI) m/z (M+)
calcd for C32H46O4SiS2 586.2607, found 586.2604.
(21) Page, P. C. B.; McKenzie, M. J.; Buckle, D. R. J. Chem. Soc., Perkin
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(22) Zampella, A.; Sepe, V.; D’Orsi, R.; Bifulco, G.; Bassarello, C.; D’Auria,
M. V. Tetrahedron: Asymmetry 2003, 14, 1787–1798.
(23) (a) Nakata, M. In Science of Synthesis, Otera, J. Ed.; Thieme: Stuttgart,
Germany, 2007; Vol. 30, pp 351-434. (b) Smith, A. B., III; Adams, C. M. Acc.
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J. Org. Chem. Vol. 73, No. 16, 2008 6295

Tanaka et al.
Homoallylalcohol 8c′ from 7c′ and 2a. Rf 0.51 (toluene/EtOAc
) 10:1); 1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 1.00 (d, J
) 6.4 Hz, 3H), 1.06 (s, 9H), 1.10 (d, J ) 7.2 Hz, 3H), 1.70-1.87
(m, 2H), 1.98-2.11 (m, 2H), 2.04 (s, 3H), 2.25 (m, 1H), 2.47-2.67
(m, 3H), 2.63 (d, J ) 2.8 Hz, 1H), 3.05-3.25 (m, 2H), 3.61 (ddd,
J ) 10.0, 10.0, 4.4 Hz, 1H), 3.72 (ddd, J ) 10.0, 6.4, 3.8 Hz, 1H),
4.31 (dd, J ) 8.2, 2.8 Hz, 1H), 5.05 (br dd, J ) 10.0 Hz, 1H), 5.08
(br d, J ) 17.0 Hz, 1H), 5.83 (d, J ) 10.2 Hz, 1H), 5.90 (ddd, J
) 17.0, 10.0, 8.0 Hz, 1H), 7.34-7.47 (m, 6H), 7.66-7.72 (m, 4H);
13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ 8.9, 17.3, 19.1,
21.1, 24.5, 26.4, 26.5, 26.8, 33.0, 41.7, 42.7, 60.3, 60.8, 71.0, 74.2,
114.5, 127.6, 129.6, 129.6, 133.4, 133.6, 135.5, 135.7, 141.9, 170.2;
IR (neat, cm-1) 3540, 3072, 2960, 2930, 2860, 1740, 1640, 1590,
1473, 1462, 1428, 1390, 1372, 1280, 1238, 1110, 1020, 968, 910,
821, 758, 700; LRMS (EI) m/z (M+) 586.2; HRMS (EI) m/z (M+)
calcd for C32H46O4SiS2 586.2607, found 586.2632.
979, 963, 912, 823, 759, 740, 702; LRMS (EI) m/z (M+) 586.2;
HRMS (EI) m/z (M+) calcd for C32H46O4SiS2 586.2607, found
586.2600.
Homoallylalcohol 10c′ from 7c′ and 2b. Rf 0.51 (toluene/EtOAc
1
) 10:1); H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 1.05 (s,
9H), 1.05 (d, J ) 7.0 Hz, 3H), 1.12 (d, J ) 6.8 Hz, 3H), 1.60-1.88
(m, 2H), 2.03 (s, 3H), 2.04-2.17 (m, 2H), 2.26 (m, 1H), 2.45-2.64
(m, 3H), 2.78 (d, J ) 2.6 Hz, 1H), 3.03-3.24 (m, 2H), 3.57 (ddd,
J ) 10.0, 10.0, 4.8 Hz, 1H), 3.67 (ddd, J ) 10.0, 6.4, 4.0 Hz, 1H),
4.28 (dd, J ) 9.6, 2.8 Hz, 1H), 4.98 (dd, J ) 9.6, 2.4 Hz, 1H),
5.02 (dd, J ) 16.6, 2.4 Hz, 1H), 5.62 (ddd, J ) 16.6, 9.6, 9.0 Hz,
1H), 5.81 (d, J ) 10.0 Hz, 1H), 7.33-7.45 (m, 6H), 7.64-7.71
(m, 4H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ 8.2, 18.2,
19.1, 21.1, 24.6, 26.4, 26.8, 26.8, 32.9, 41.5, 42.7, 60.2, 60.7, 71.1,
74.3, 114.9, 127.6, 129.6, 133.4, 133.6, 135.6, 135.7, 141.6, 170.2;
IR (neat, cm-1) 3500, 3073, 3050, 2960, 2930, 2860, 1740, 1640,
1590, 1472, 1460, 1440, 1428, 1390, 1373, 1310, 1280, 1238, 1113,
1085, 1020, 1000, 970, 912, 822, 759, 738, 701; LRMS (EI) m/z
(M+) 586.1; HRMS calcd for C32H46O4SiS2 586.2607, found
586.2584.
Homoallylalcohols 10a and 11a from 7a and 2b. Rf 0.52
1
(toluene/EtOAc ) 10:1); H NMR (300 MHz, CDCl3, CHCl3 )
7.26) δ 0.72 (s, 6H), 0.96, 0.98, 1.02, and 1.12 (each d, J ) 7.0,
7.2, 7.0, and 6.8 Hz, each 3H), 1.19 (s, 6H), 1.86-1.98 (m, 2H),
2.22-2.40 (m, 2H), 3.10 and 3.22 (each br, each 1H), 3.43 (m,
4H), 3.53-3.62 and 3.75 (m and br d, J ) 11.0 Hz, each 1H),
3.62 (br d, J ) 11.0 Hz, 2H), 4.46 and 4.58 (each d, J ) 3.0 and
3.4 Hz, each 1H), 4.95 and 5.45 (each dd, J ) 10.0, 2.0 and 10.0,
1.2 Hz, each 1H), 5.04 and 5.06 (each br d, J ) 16.0 and 18.0 Hz,
each 1H), 5.60 and 5.90 (each ddd, J ) 16.0, 10.0, 9.0 and 18.0,
10.0, 7.0 Hz, each 1H); 13C NMR (75 MHz, CDCl3, CDCl3 )
77.00) δ 6.7, 11.4, 12.4, 17.7, 21.7, 21.7, 22.9, 22.9, 30.3, 30.3,
38.9, 39.7, 40.2, 41.9, 74.1, 75.5, 77.1, 77.2, 77.3, 77.3, 104.2,
105.6, 114.1, 114.6, 141.1, 142.3; IR (neat, cm-1) 3520, 3080, 2959,
2850, 1640, 1465, 1392, 1365, 1310, 1261, 1236, 1219, 1165, 1110,
1040, 1020, 995, 965, 910, 810, 790; LRMS (EI) m/z (M+) 228.1;
HRMS (EI) m/z (M+) calcd for C13H24O3 228.1726, found 228.1723.
Homoallylalcohols 10b and 11b from 7b and 2b. The NMR
chemical shifts of each 10b and 11b were determined by using the
spectra of a mixture of 10b and 11b. 10b: Rf 0.46 (toluene/EtOAc
) 10:1); 1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 0.98 (d, J
) 7.0 Hz, 3H), 1.07 (d, J ) 7.0 Hz, 3H), 1.76-1.96 (m, 2H),
1.96-2.19 (m, 2H), 2.43 (m, 1H), 2.80-2.94 (m, 4H), 3.63 (dd, J
) 8.0, 3.0 Hz, 1H), 4.66 (d, J ) 2.4 Hz, 1H), 5.13 (br d, J ) 17.4
Hz, 1H), 5.15 (br d, J ) 11.2 Hz, 1H), 5.91 (ddd, J ) 17.4, 11.2,
6.2 Hz, 1H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ 10.5,
12.8, 26.4, 30.7, 31.5, 38.9, 41.4, 52.3, 74.2, 115.2, 141.8. 11b: Rf
0.46 (toluene/EtOAc ) 10:1); 1H NMR (300 MHz, CDCl3, CHCl3
) 7.26) δ 1.09 (d, J ) 7.0 Hz, 6H),1.76-1.96 (m, 2H), 1.96-2.19
(m, 2H), 2.34 (m, 1H), 2.80-3.08 (m, 4H), 3.74 (dd, J ) 8.2, 2.9
Hz, 1H), 4.14 (d, J ) 6.2 Hz, 1H), 5.01 (dd, J ) 10.4, 1.5 Hz,
1H), 5.07 (br d, J ) 16.4 Hz, 1H), 5.63 (ddd, J ) 16.4, 10.4, 8.4
Hz, 1H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ 10.1, 17.0,
26.1, 30.6, 31.0, 40.3, 41.8, 53.6, 75.6, 115.1, 140.7. Mixture of
10b and 11b: IR (neat, cm-1) 3470, 3078, 2970, 2938, 2898, 2830,
1640, 1458, 1420, 1381, 1318, 1278, 1242, 1190, 1110, 1090, 1000,
978, 913, 876, 858, 816, 760; LRMS (EI) m/z (M+) 232.1; HRMS
(EI) m/z (M+) calcd for C11H20OS2 232.0956, found 232.0961.
Homoallylalcohol 10c from 7c and 2b. Rf 0.51 (toluene/EtOAc
Conversion of Homoallylalcohol 8b: Dedithioacetalization.
Silyl Ether 12. To a stirred solution of 8b (411 mg, 1.77 mmol) in
dry CH2Cl2 (17.7 mL) were added at 0 °C N-ethyldiisopropylamine
(1.30 mL, 7.43 mmol) and tert-butyldimethylsilyl trifluoromethane-
sulfonate (1.06 mL, 4.60 mmol). After 4 h at 0 °C, saturated aqueous
NH4Cl was added and the mixture was extracted with CHCl3. The
extracts were washed with saturated aqueous NaCl, dried over
Na2SO4, and concentrated. The residue was purified by column
chromatography on silica gel (25 g, hexane/EtOAc ) 50:1) to afford
12 (610 mg, 99%) as a colorless syrup: Rf 0.71 (hexane/EtOAc )
1
4:1); H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 0.07 (s, 3H),
0.11 (s, 3H), 0.90 (s, 9H), 1.02 (d, J ) 7.0 Hz, 3H), 1.07 (d, J )
7.0 Hz, 3H), 1.75-2.02 (m, 2H), 2.02-2.14 (m, 1H), 2.39 (m, 1H),
2.74-2.92 (m, 4H), 3.92 (dd, J ) 4.3, 4.1 Hz, 1H), 4.04 (d, J )
6.8 Hz, 1H), 5.02 (dd, J ) 9.4, 1.4 Hz, 1H), 5.04 (ddd, J ) 17.4,
1.4, 0.8 Hz, 1H), 5.89 (ddd, J ) 17.4, 9.4, 7.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3, CDCl3 ) 77.00) δ -3.8, -3.6, 12.8, 16.2, 18.4,
26.1, 26.1, 30.4, 30.9, 41.0, 43.2, 52.6, 75.3, 114.4, 141.3; IR (neat,
cm-1) 3075, 2955, 2930, 2895, 2857, 1639, 1471, 1461, 1421, 1387,
1380, 1360, 1279, 1253, 1188, 1100, 1068, 1041, 1029, 1004, 940,
910, 869, 839, 774, 668; LRMS (EI) m/z (M+) 346.2; HRMS (EI)
m/z (M+) calcd for C17H34OSiS2 346.1821, found 346.1824.
Aldehyde 13.19 To a stirred solution of 12 (8.5 mg, 0.0245
mmol) and CaCO3 (13.0 mg, 0.123 mmol) in MeCN/H2O ) 9:1
(0.35 mL) was added at 0 °C MeI (0.015 mL, 0.245 mmol) and
the mixture was heated at 45 °C. After 12 h at 45 °C, the mixture
was diluted with hexane (0.50 mL) and then directly subjected to
column chromatography on silica gel (0.5 g, hexane/TEA ) 20:1)
to afford 13 (3.6 mg, 57%) as a colorless syrup: Rf 0.60 (toluene/
1
EtOAc ) 10:1); H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ
0.03 (s, 3H), 0.08 (s, 3H), 0.89 (s, 9H), 1.04 (d, J ) 7.0 Hz, 3H),
1.09 (d, J ) 7.0 Hz, 3H), 2.40 (m, 1H), 2.49 (m, 1H), 3.99 (dd, J
) 4.0, 4.0 Hz, 1H), 5.02 (br d, J ) 16.0 Hz, 1H), 5.04 (br d, J )
10.2 Hz, 1H), 5.78 (ddd, J ) 16.0, 10.2, 8.0 Hz, 1H), 9.78 (br s,
1H).
Conversion of 12: Oxidative Cleavage of Olefin. Aldehyde
14. A solution of 12 (50.0 mg, 0.143 mmol) in MeOH (1.43 mL)
was cooled to -78 °C and ozone was bubbled through the solution
until a blue color was observed. After 10 min at -78 °C, oxygen
was bubbled through the solution until no blue color remained. After
addition of dimethylsulfide (0.210 mL), the reaction mixture was
warmed to rt. After 7 h at rt, saturated aqueous NaHCO3 was added
and the mixture was extracted with EtOAc. The residue was purified
by column chromatography on silica gel (1 g, EtOAc) to afford 14
(46.2 mg, 88%: a 7:3 mixture of diastereomers) as colorless crystals.
The NMR chemical shifts of each isomer were determined by using
the spectra of the mixture. Major isomer of 14: Rf 0.24 (EtOAc);
1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 0.09 (s, 3H), 0.10
(a, 3H), 0.87 (s, 9H), 1.09 (d, J ) 6.6 Hz, 3H), 1.17 (d, J ) 6.6
1
) 10:1); H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 1.07 (s,
9H), 1.10 (d, J ) 6.0 Hz, 3H), 1.22 (d, J ) 6.2 Hz, 3H), 1.72-1.88
(m, 2H), 1.96-2.07 (m, 2H), 2.06 (s, 3H), 2.25 (d, J ) 2.6 Hz,
1H), 2.19-2.34 (m, 1H), 2.45-2.60 (m, 3H), 3.04-3.28 (m 2H),
3.63 (ddd, J ) 10.0, 10.0, 4.8 Hz, 1H), 3.71 (ddd, J ) 10.0, 7.0,
4.0 Hz, 1H), 4.11 (dd, J ) 10.4, 2.6 Hz, 1H), 4.98 (dd, J ) 10.2,
1.8 Hz, 1H), 5.07 (dd, J ) 17.4, 1.8 Hz, 1H), 5.56 (ddd, J ) 17.4,
10.2, 10.2 Hz, 1H), 5.92 (d, J ) 9.0 Hz, 1H), 7.34-7.47 (m, 6H),
7.65-7.73 (m, 4H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00)
δ 8.7, 18.2, 19.1, 21.1, 24.3, 26.1, 26.6, 26.8, 33.3, 41.5, 42.3, 60.7,
60.9, 72.1, 75.3, 115.1, 127.6, 129.6, 129.6, 133.4, 133.6, 135.5,
135.7, 140.8, 170.1; IR (neat, cm-1) 3560, 3078, 2960, 2930, 2860,
1743, 1640, 1590, 1472, 1460, 1427, 1373, 1280, 1233, 1111, 1019,
6296 J. Org. Chem. Vol. 73, No. 16, 2008

DiastereoselectiVe Crotylation with K Crotyltrifluoroborates
Hz, 3H), 2.06-2.70 (m, 6H), 2.74 (m, 1H), 3.44 (m, 1H), 3.45 (d,
J ) 3.5 Hz, 1H), 4.17 (dd, J ) 8.2, 2.6 Hz, 1H), 9.91 (d, J ) 1.0
Hz, 1H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ -4.4,
-4.4, 8.7, 12.6, 18.0, 25.7, 29.4, 29.5, 34.6, 52.7, 54.5, 68.2, 73.7,
202.7. Minor isomer of 14: Rf 0.24 (EtOAc); 1H NMR (300 MHz,
CDCl3, CHCl3 ) 7.26) δ 0.08 (s, 3H), 0.12 (s, 3H), 0.87 (s, 9H),
1.12 (d, J ) 6.6 Hz, 3H), 1.27 (d, J ) 6.6 Hz, 3H), 2.06-2.70 (m,
6H), 2.82 (m, 1H), 3.34 (m, 1H), 3.68 (d, J ) 4.0 Hz, 1H), 4.44
(dd, J ) 6.6, 3.6 Hz, 1H), 9.82 (d, J ) 1.6 Hz, 1H); 13C NMR (75
MHz, CDCl3, CDCl3 ) 77.00) δ -4.0, -3.9, 10.5, 13.6, 18.2, 25.9,
28.6, 30.0, 41.2, 52.0, 53.7, 67.3, 73.9, 204.7. Mixture of two
isomers of 14: IR (KBr, cm-1) 3430, 2960, 2934, 2860, 2740, 1719,
1475, 1463, 1428, 1390, 1362, 1258, 1095, 1078, 1038, 960, 940,
909, 839, 779, 670; LRMS (EI) m/z (M+) 364.2; HRMS (EI) m/z
(M+) calcd for C16H32O3SiS2 364.1562, found 364.1578.
EtOAc ) 4:1) to afford 16 (40.8 mg, 84%) as colorless crystals:
Rf 0.69 (hexane/EtOAc ) 4:1); 1H NMR (300 MHz, CDCl3, CHCl3
) 7.26) δ -0.07 (s, 3H), -0.04 (s, 3H), 0.79 (s, 9H), 0.92 (d, J )
7.0 Hz, 3H), 1.08 (s, 9H), 1.09 (d, J ) 7.0 Hz, 3H), 1.98 (m, 1H),
2.49 (m, 1H), 3.50 (dd, J ) 10.0, 7.0 Hz, 1H), 3.70 (dd, J ) 10.0,
6.2 Hz, 1H), 4.26 (dd, J ) 6.2, 3.2 Hz, 1H), 7.34-7.48 (m, 6H),
7.62-7.70 (m, 4H), 9.67 (br s, 1H); 13C NMR (75 MHz, CDCl3,
CDCl3 ) 77.00) δ -4.4, -4.3, 8.1, 13.4, 18.1, 19.2, 25.8, 26.9,
40.9, 49.7, 65.9, 71.8, 127.6, 129.6, 129.7, 133.6, 135.6, 135.6,
205.0; IR (neat, cm-1) 3078, 3050, 2958, 2930, 2890, 2860, 2710,
1728, 1590, 1474, 1462, 1428, 1390, 1361, 1300, 1258, 1219, 1189,
1113, 1088, 1030, 1009, 959, 940, 912, 839, 778, 760, 720, 700,
670; LRMS (EI) m/z (M+) 498.2; HRMS (EI) m/z (M+) calcd for
C29H46O3Si2 498.2986, found 498.3010.
Conversion of 8b: Coupling Reaction with Aldehyde 17.
Diols 18 and 18′. To a stirred solution of 8b (18.5 mg, 0.0796
mmol) in dry THF (0.90 mL) was added at rt 1.65 M n-BuLi in
hexane (0.0965 mL, 0.159 mmol). After 5 min at -20 °C, a solution
of 3-(tert-butyldiphenylsiloxy)propanal25 (17, 49.7 mg, 0.159 mmol)
in dry THF (0.20 mL) was added and the mixture was warmed to
rt. After 30 min at rt, saturated aqueous NH4Cl was added and the
mixture was extracted with EtOAc. The extracts were washed with
saturated aqueous NaCl, dried over Na2SO4, and concentrated. The
residue was purified by column chromatography on silica gel (10
g, hexane/EtOAc ) 4:1) to afford 18 and 18′ (20.8 mg, 66%: a 1:2
mixture of diastereomers) as a colorless syrup. The analytical data
of each isolated 18 and 18′ derived from the different route are
shown below (for details of the different route, see the Supporting
Information). 18: colorless crystals: Rf 0.37 (hexane/EtOAc ) 4:1);
1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 1.04 (s, 9H), 1.07
(d, J ) 6.6 Hz, 3H), 1.21 (d, J ) 7.2 Hz, 3H), 1.83-2.05 (m, 2H),
2.11 (m, 1H), 2.25-2.40 (m, 2H), 2.48 (m, 1H), 2.66-2.85 (m,
4H), 3.83-4.00 (m, 2H), 4.22 (br d, J ) 10.4 Hz, 1H), 4.25 (br d,
J ) 10.0 Hz, 1H), 5.10 (dd, J ) 10.0, 1.6 Hz, 1H), 5.14 (dd, J )
17.6, 1.6 Hz, 1H), 5.87 (ddd, J ) 17.6, 10.0, 8.2 Hz, 1H), 7.35-7.48
(m, 6H), 7.64-7.72 (m, 4H); 13C NMR (75 MHz, CDCl3, CDCl3
) 77.00) δ 8.2, 17.6, 19.0, 24.8, 25.2, 26.2, 26.8, 34.2, 40.7, 43.2,
63.2, 63.2, 72.6, 73.0, 115.3, 127.7, 129.7, 133.0, 133.1, 135.5,
135.5, 142.2; IR (neat, cm-1) 3380, 3073, 2960, 2930, 2860, 1640,
1590, 1473, 1460, 1427, 1390, 1313, 1278, 1112, 999, 910, 822,
738, 700; LRMS (EI) m/z (M+) 544.1; HRMS (EI) m/z (M+) calcd
for C30H44O3SiS2 544.2501, found 544.2508. 18′: colorless crystals:
Rf 0.37 (hexane/EtOAc ) 4:1); 1H NMR (300 MHz, CDCl3, CHCl3
) 7.26) δ 1.01 (d, J ) 6.2 Hz, 3H), 1.06 (s, 9H), 1.22 (d, J ) 7.0
Hz, 3H), 1.83-2.03 (m, 3H), 2.30 (m, 1H), 2.36-2.49 (m, 2H),
2.64 (ddd, J ) 14.4, 6.2, 4.6 Hz, 1H), 2.69-2.84 (m, 2H), 2.88
(ddd, J ) 14.4, 6.2, 4.2 Hz, 1H), 3.28 (br, 1H), 3.81-3.97 (m,
3H), 4.09 (d, J ) 8.8 Hz, 1H), 4.33 (d, J ) 10.4 Hz, 1H), 5.11
(dd, J ) 10.0, 2.0 Hz, 1H), 5.13 (ddd, J ) 17.6, 2.0, 0.8 Hz, 1H),
5.83 (ddd, J ) 17.6, 10.0, 8.2 Hz, 1H), 7.34-7.46 (m, 6H),
7.64-7.72 (m, 4H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00)
δ 9.8, 17.2, 19.2, 24.7, 25.8, 25.8, 26.8, 34.7, 42.0, 42.6, 61.8, 62.2,
72.2, 72.5, 115.5, 127.6, 129.6, 133.5, 133.6, 135.5, 142.1; IR (KBr,
cm-1) 3410, 3078, 2960, 2930, 2860, 1640, 1590, 1473, 1462, 1427,
1390, 1278, 1219, 1112, 990, 910, 822, 758, 738, 703; LRMS (EI)
m/z (M+) 544.2; HRMS (EI) m/z (M+) calcd for C30H44O3SiS2
544.2501, found 544.2517.
Silyl Ether 15. To a stirred solution of 14 (46.2 mg, 0.126 mmol)
in EtOH (1.26 mL) was added at 0 °C NaBH4 (4.99 mg, 0.126
mmol). After 10 min at rt, saturated aqueous NH4Cl was added
and the mixture was extracted with EtOAc. The extracts were
washed with saturated aqueous NaCl, dried over Na2SO4, and
concentrated. The residue was purified by column chromatography
on silica gel (10 g, CHCl3/MeOH ) 4:1) to afford alcohol (42.8
mg, 93%: a 7:3 mixture of diastereomers) as a colorless syrup. This
alcohol (147 mg, 0.419 mmol) was dissolved in dry CH2Cl2 (17.7
mL) and to this solution were added at 0 °C imidazole (57.1 mg,
0.838 mmol) and tert-butyldiphenylsilyl chloride (0.164 mL, 0.629
mmol). After 2 h at rt, water was added and the mixture was
extracted with CHCl3. The extracts were washed with saturated
aqueous NaCl, dried over Na2SO4, and concentrated. The residue
was purified by column chromatography on silica gel (15 g, hexane/
EtOAc ) 1:1) to afford 15 (210 mg, 85%; a 7:3 mixture of
diastereomers) as colorless solids. For analytical samples, the
isomers were partially separated by column chromatography
(hexane/EtOAc ) 1:1) to give colorless crystals. Major isomer of
1
15: Rf 0.54 (hexane/EtOAc ) 1:1); H NMR (300 MHz, CDCl3,
CHCl3 ) 7.26) δ 0.03 (s, 3H), 0.10 (s, 3H), 0.85 (s, 9H), 0.89 (d,
J ) 7.0 Hz, 3H), 1.01 (d, J ) 7.0 Hz, 3H), 1.09 (s, 9H), 2.04-2.54
(m, 6H), 2.90 (m, 1H), 3.40 (br ddd, J ) 13.0, 4.0, 4.0 Hz, 1H),
3.54 (dd, J ) 11.0, 7.2 Hz, 1H), 3.75 (d, J ) 2.6 Hz, 1H), 3.84
(dd, J ) 11.0, 8.2 Hz, 1H), 4.12 (dd, J ) 5.8, 2.4 Hz, 1H),
7.34-7.46 (m, 6H), 7.64-7.73 (m, 4H); 13C NMR (300 MHz,
CDCl3, CDCl3 ) 77.00) δ -4.2, -4.0, 11.8, 11.9, 18.2, 19.3, 26.0,
27.0, 29.6, 31.7, 41.9, 54.1, 65.7, 71.3, 73.2, 127.7, 127.7, 129.6,
129.6, 133.6, 133.8, 135.6; IR (neat, cm-1) 3070, 3050, 2959, 2930,
2858, 1590, 1472, 1464, 1428, 1390, 1360, 1258, 1219, 1185, 1160,
1110, 1080, 1066, 1040, 1008, 940, 870, 840, 778, 758, 700, 692,
662; LRMS (EI) m/z (M+) 604.3; HRMS (EI) m/z (M+) calcd for
C32H52O3Si2S2 604.2897, found 604.2876. Minor isomer of 15: Rf
1
0.39 (hexane/EtOAc ) 1:1); H NMR (300 MHz, CDCl3, CHCl3
) 7.26) δ -0.02 (s, 3H), 0.09 (s, 3H), 0.84 (s, 9H), 0.88 (d, J )
6.6 Hz, 3H), 1.07 (s, 9H), 1.20 (d, J ) 6.6 Hz, 3H), 1.96-2.24 (m,
2H), 2.35-2.71 (m, 5H), 3.31 (m, 1H), 3.45 (dd, J ) 10.6, 7.0 Hz,
1H), 3.67 (d, J ) 5.0 Hz, 1H), 3.82 (dd, J ) 10.6, 6.6 Hz, 1H),
4.21 (dd, J ) 4.2, 4.2 Hz, 1H), 7.33-7.46 (m, 6H), 7.66-7.73 (m,
4H); 13C NMR (300 MHz, CDCl3, CDCl3 ) 77.00) δ -3.8, -3.7,
13.5, 13.7, 18.4, 19.2, 26.1, 26.9, 27.9, 29.4, 37.3, 41.2, 53.1, 65.7,
69.97, 73.1, 127.6, 129.5, 129.5, 133.9, 135.6, 135.7; IR (neat,
cm-1) 3078, 3050, 2958, 2932, 2858, 1717, 1590, 1472, 1462, 1428,
1390, 1360, 1252, 1219, 1188, 1110, 1080, 1038, 1008, 940, 910,
858, 838, 768, 759, 704, 690, 663, 617; LRMS (EI) m/z (M+) 604.3;
HRMS (EI) m/z (M+) calcd for C32H52O3Si2S2 604.2897, found
604.2889.
Silyl Ethers 19 and 19′. To a stirred solution of a mixture of
18 and 18′ (8.3 mg, 0.0152 mmol) in dry CH2Cl2 (0.152 mL) were
added at rt N-ethyldiisopropylamine (0.0223 mL, 0.128 mmol) and
tert-butyldimethylsilyl trifluoromethanesulfonate (0.0182 mL, 0.0790
mmol). After 7 h at rt, saturated aqueous NH4Cl was added and
the mixture was extracted with CHCl3. The extracts were washed
with saturated aqueous NaCl, dried over Na2SO4, and concentrated.
The residue was purified by column chromatography on silica gel
(3 g, hexane/EtOAc ) 50:1) to afford 19 and 19′ (11.6 mg, 99%:
a 1:2 mixture of diastereomers) as a colorless syrup. The NMR
chemical shifts of each 19 and 19′ were determined by using the
spectra of a mixture of 19 and 19′. 19: Rf 0.95 (hexane/EtOAc )
Aldehyde 16.22 To a stirred solution of 15 (58.8 mg, 0.0972
mmol) in 30:1 acetone-H2O (1.95 mL) was added at 0 °C
N-bromosuccinimide (103.8 mg, 0.583 mmol). After 5 min at 0
°C, saturated aqueous NaHCO3 was added and the mixture was
extracted with EtOAc. The extracts were washed with saturated
aqueous NaCl, dried over Na2SO4, and concentrated. The residue
was purified by column chromatography on silica gel (10 g, hexane/
J. Org. Chem. Vol. 73, No. 16, 2008 6297

Tanaka et al.
1
4:1); H NMR (270 MHz, CDCl3, CHCl3 ) 7.26) δ 0.00 (s, 3H),
10 min at -78 °C, oxygen was bubbled through the solution until
no blue color remained. After addition of triphenylphosphine (15.8
mg, 0.0602 mmol), the mixture was warmed to -30 °C. Saturated
aqueous NaHCO3 was added and the mixture was extracted with
EtOAc. The extracts were washed with saturated aqueous NaCl,
dried over Na2SO4, and concentrated. The residue was purified by
column chromatography on silica gel (1 g, hexane/EtOAc ) 3:1)
to afford 20 and 20′ (36.5 mg, 89%: a 1:2 mixture of diastereomers)
as a colorless syrup. The NMR chemical shifts of each 20 and 20′
were determined by using the spectra of a mixture of 20 and 20′.
0.15 (s, 3H), 0.16 (s, 3H), 0.22 (s, 3H), 0.80 (s, 9H), 0.91 (m, 3H),
0.92 (s, 9H), 1.02 (d, J ) 7.0 Hz, 3H), 1.06 (s, 9H), 1.72-1.88
(m, 2H), 1.94 (m, 1H), 2.11 (m, 1H), 2.26-2.44 (m, 2H), 2.59 (m,
1H), 2.78 (m, 1H), 2.89-3.10 (m, 2H), 3.73 (dd, J ) 9.2, 4.2 Hz,
1H), 3.78 (dd, J ) 9.2, 5.0 Hz, 1H), 4.53 (dd, J ) 2.2, 2.2 Hz,
1H), 4.61 (br d, J ) 8.4 Hz, 1H), 4.98 (br d, J ) 17.0 Hz, 1H),
4.99 (br d, J ) 8.4 Hz, 1H), 5.94 (ddd, J ) 17.0, 8.4, 7.0 Hz, 1H),
7.33-7.46 (m, 6H), 7.61-7.72 (m, 4H); 13C NMR (75 MHz,
CDCl3, CDCl3 ) 77.00) δ -4.6, -3.9, -2.9, -2.9, 11.8, 15.4,
18.1, 18.3, 18,6, 19.1, 25.7, 26.3, 26.9, 27.4, 39.5, 41.9, 47.1, 62.1,
63.5, 74.3, 114.5, 127.6, 127.6, 129.6, 129.7, 133.7, 133.8, 135.6,
1
20: Rf 0.42 (hexane/EtOAc ) 10:1); H NMR (300 MHz, CDCl3,
CHCl3 ) 7.26) δ 0.04 (s, 3H), 0.07 (s, 3H), 0.08 (s, 3H), 0.13 (s,
3 H), 0.89 (s, 9H), 0.89 (s, 9H), 1.06 (s, 9H), 1.07 (d, J ) 7.0 Hz,
3H) 1.14 (d, J ) 7.0 Hz, 3H), 1.62-1.81 (m, 1H), 1.88-2.02 (m,
1H), 2.32 (m, 1H), 3.12 (m, 1H), 3.65-3.86 (m, 2H), 4.25 (dd, J
) 8.0, 2,4 Hz, 1H), 4.42-4.52 (m, 1H), 7.33-7.48 (m, 6H),
7.63-7.72 (m, 4H), 9.68 (d, J ) 2.4 Hz, 1H); 13C NMR (75 MHz,
CDCl3, CDCl3 ) 77.00) δ -4.9, -4.7, -4.1, -3.9, 11.4, 14.8,
18.1, 19.1, 25.8, 26.0, 26.9, 37.4, 46.2, 51.7, 60.0, 74.1, 74.6, 127.7,
129.6, 133.7, 135.6, 203.5, 214.6. 20′: Rf 0.42 (hexane/EtOAc )
10:1); 1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26) δ 0.05 (s, 3H),
0.08 (s, 3H), 0.09 (s, 3H), 0.11 (s, 3 H), 0.88 (s, 9H), 0.89 (s, 9H),
1.06 (s, 9H), 1.09 (d, J ) 6.8 Hz, 3H), 1.11 (d, J ) 7.0 Hz, 3H),
1.62-1.81 (m, 1H), 1.88-2.02 (m, 1H), 2.32 (m, 1H), 3.19 (m,
1H), 3.65-3.86 (m, 2H), 4.08 (dd, J ) 8.0, 2.4 Hz, 1H), 4.42-4.52
(m, 1H), 7.33-7.48 (m, 6H), 7.63-7.72 (m, 4H), 9.69 (d, J ) 3.0
Hz, 1H); 13C NMR (75 MHz, CDCl3, CDCl3 ) 77.00) δ -4.7,
-4.7, -4.1, -3.8, 12.0, 15.1, 18.3, 19.2, 25.8, 25.9, 26.0, 26.9,
36.8, 45.7, 51.1, 60.2, 75.1, 75.8, 127.7, 129.6, 133.7, 135.6, 203.5,
214.3. Mixture of 20 and 20′: IR (neat, cm-1) 3078, 3052, 2958,
2932, 2890, 2860, 1723, 1590, 1473, 1464, 1428, 1390, 1361, 1258,
1114, 1042, 1005, 940, 839, 779, 740, 701; LRMS (EI) m/z (M+)
684.2; HRMS (EI) m/z (M+) calcd for C38H64O5Si3 684.4062, found
684.4046.
1
140.5. 19′: Rf 0.95 (hexane/EtOAc ) 4:1); H NMR (270 MHz,
CDCl3, CHCl3 ) 7.26) δ 0.04 (s, 3H), 0.14 (s, 3H), 0.15 (s, 3H),
0.21 (s, 3H), 0.83 (s, 9H), 0.91 (s, 9H), 0.97 (d, J ) 7.2 Hz, 3H),
1.03 (d, J ) 7.2 Hz, 3H), 1.06 (s, 9H), 1.66 (m, 1H), 1.80 (m, 1H),
1.93-2.08 (m, 2H), 2.29-2.63 (m, 4H), 2.76 (m, 1H), 2.95 (m,
1H), 3.73-3.87 (m, 2H), 4.43 (br d, J ) 8.0 Hz, 1H), 4.49 (dd, J
) 2.2, 2.2 Hz, 1H), 4.98 (br d, J ) 18.0 Hz, 1H), 5.00 (br d, J )
8.4 Hz, 1H), 5.94 (ddd, J ) 18.0, 8.4, 7.0 Hz, 1H), 7.33-7.46 (m,
6H), 7.66-7.72 (m, 4H); 13C NMR (75 MHz, CDCl3, CDCl3 )
77.00) δ -4.1, -4.0, -3.4, -3.4, 12.4, 15.7, 18.7, 18.8, 18.8, 19.2,
25.1, 25.7, 26.2, 26.4, 26.9, 36.9, 42.0, 47.2, 62.0, 63.3, 74.0, 114.4,
127.6, 127.6, 129.5, 129.6, 133.9, 134.0, 135.6, 135.7, 140.7.
Mixture of 19 and 19′: IR (neat, cm-1) 3078, 3050, 2958, 2930,
2894, 2859, 1639, 1590, 1472, 1462, 1428, 1390, 1360, 1278, 1253,
1218, 1186, 1110, 1043, 1003, 959, 940, 914, 882, 838, 777, 760,
740, 701, 690, 664; LRMS (EI) m/z (M+) 772.3; HRMS (EI) m/z
(M+) calcd for C42H72O3Si3S2 772.4231, found 772.4233.
Aldehydes 20 and 20′. To a stirred solution of a mixture of 19
and 19′ (64.3 mg, 0.0831 mmol) in 9:1 THF-H2O (0.66 mL) was
added at -5 °C (CF3CO2)2IPh (214.4 mg, 0.499 mmol). After 45
min at -5 °C, saturated aqueous NaHCO3 was added and the
mixture was extracted with EtOAc. The extracts were washed with
saturated aqueous NaCl, dried over Na2SO4, and concentrated. The
residue was purified by column chromatography on silica gel (10
g, hexane/EtOAc ) 4:1) to afford ketone (51.1 mg, 90%: a 1:2
mixture of diasteromers) as a colorless syrup. A portion of this
ketone (41.1 mg, 0.0602 mmol) was dissolved in 9:1
CH2Cl2-MeOH (6.00 mL) and cooled to -78 °C. Ozone was
bubbled through the solution until a blue color was observed. After
Supporting Information Available: Characterization data
of the adducts 3-6, structure determination of the adducts, and
preparation of the substrates 7a-c and 7c′. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO801106B
6298 J. Org. Chem. Vol. 73, No. 16, 2008