Stereoselective Synthesis of Stereotriad Subunits of Polyketides through Additions of Nonracemic Allenylsilanes to (R)- and (S)-2-Methyl-3-oxygenated Propanals

Full text of DOI:10.1021/jo991543y

630
J . Org. Chem. 2000, 65, 630-633
than the corresponding stannanes, allenylsilanes have
Ster eoselective Syn th esis of Ster eotr ia d
been prepared, and their additions to aldehydes have
been examined.5 Such additions afford, as expected,
mainly syn adducts. However, studies on additions of
enantioenriched allenylsilanes to enantioenriched R-
methyl-substituted aldehydes appropriate for polyketide
synthesis have not been reported.6 A possible problem
with this approach is the relative unreactivity of alle-
nylsilanes compared to allenylstannanes. Whereas the
latter react with aldehydes in the presence of fairly mild
Lewis acids (BF3‚OEt2, MgBr2), the latter additions
typically require TiCl4, a much stronger Lewis acid. Thus,
concerns about protecting group compatibility and alde-
hyde racemization come to mind.
The enantioenriched allenylsilanes (M)-2a and (M)-2b
were prepared by the silylcuprate SN2′ displacement
method of Fleming (eq 2).7 Propargylic mesylates 1a and
1b of >95% ee were employed in this work. It has been
shown that such displacements proceed with nearly 100%
inversion with stannyl cuprates and propargylic mesy-
lates,1 and with silyl cuprates and allylic esters.7 In the
present case, the ee of the allenylsilanes was shown to
be >95% by GC analysis on an R-DEX column.
Su bu n its of P olyk etid es th r ou gh Ad d ition s
of Non r a cem ic Allen ylsila n es to (R)- a n d
(S)-2-Meth yl-3-oxygen a ted P r op a n a ls
J ames A. Marshall* and Karin Maxson
Department of Chemistry, University of Virginia
Charlottesville, Virginia 22904
Received October 5, 1999
In 1992, we reported a method for the synthesis of the
diastereomeric stereotriad subunits of polyketide natural
products.1 The approach utilized enantioenriched allenyl
tributyltin reagents and R-methyl, â-oxygenated alde-
hydes as the two reacting partners (eq 1). Lewis acid
promoted additions led to the syn,syn or syn,anti dia-
stereomers through acyclic Felkin-Anh or acyclic che-
lation-controlled transition states. The anti,syn and
anti,anti diastereomers were secured through transmeta-
lation of the tributylstannanes with SnCl4 and subse-
quent in situ addition of the derived allenyl trichlorotin
reagents to the aforementioned aldehydes. These latter
additions proceed via cyclic transition states under
Felkin-Anh or chelation control.
Preliminary screening was conducted with allenylsi-
lane 2a and cyclohexanecarboxaldehyde. Use of BF3‚OEt,
BiBr3,8 or Sc(OTfl)3 as Lewis acid promoters gave no
9
adducts at -78 °C and led to multiple decomposition
products at temperatures ranging from 0 to 25 °C. A
systematic examination of temperature was not carried
out as the reaction proceeded readily when TiCl4 was
employed at -78 °C. Under these conditions, allenylsi-
lane (M)-2a underwent addition to the ODPS aldehyde
(R)-3a 10 to afford the syn,syn adduct 4 in 70% yield, as
the sole detectable stereoisomer (eq 3). The stereochem-
istry is assigned in consideration of the likely transition
state and by analogy to the related allenylstannane
addition.1
Subsequent studies led to the development of methods
for the in situ formation of nonracemic allenylzinc,2
indium,3 and chlorosilane4 reagents and their addition
to aldehydes to yield anti adducts. We were thus able to
circumvent the use of environmentally objectionable
tributyl tin compounds for the preparation of these
diastereomers. However, alternative allenylmetal re-
agents for the synthesis of syn adducts were not avail-
able. These reactions proceed by an acyclic transition
state and require the metal to be relatively non-Lewis
acidic. The Bu3Sn moiety nicely fits this requirement. In
addition, the hyperconjugative electron donation by the
Bu3Sn moiety enhances double bond reactivity and
contributes to the rigidity of the transition state resulting
in highly diastereoselective additions.
(5) Danheiser, R. L.; Carini, D. J .; Kwasigroch, C. A. J . Org. Chem.
1986, 51, 3870.
(6) Fleming and Buckle have shown that (P)-1-trimethylsilyl-1,2-
butadiene adds to isobutyraldehyde to afford the syn homopropargylic
alcohol adduct by an anti SE2′ pathway. Buckle, M. J . C.; Fleming, I.
Tetrahedron Lett. 1993, 34, 2383.
(7) Fleming, I.; Terrett, N. K. J . Organomet. Chem. 1984, 264, 99.
Fleming, I.; Waterson, D. J . Chem. Soc., Perkin Trans. 1 1984, 1809.
(8) Komatsu, N.; Uda, M.; Suzuki, H.; Takahashi, T.; Domae, T.;
Wada, M. Tetrahedron Lett. 1997, 38, 7215.
An obvious replacement for Bu3Sn in these additions
would be an R3Si grouping. Though somewhat less reactive
* To whom correspondence should be addressed. E-mail: jam5x@
virginia.edu.
(1) Marshall, J . A.; Wang, X.-j. J . Org. Chem. 1992, 57, 1242.
(2) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1998, 63, 3812.
Marshall, J . A.; Adams, N. D. J . Org. Chem. 1999, 64, 5201.
(3) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 696.
(4) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1997, 62, 8976.
(9) Aggarwal, V. K.; Vennall, G. P. Tetrahedron Lett. 1996, 37, 3745.
(10) Roush, W. R.; Palkowitz, A. D.; Palmer, M. A. J . J . Org. Chem.
1987, 52, 316.
10.1021/jo991543y CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/23/1999

Notes
Addition of allenylsilane (M)-2a to the enantiomeric
aldehyde (S)-3a led to an 80:20 mixture of syn,anti and
anti,syn adducts 5a and 6 (eq 4). These results closely
parallel the mismatched BF3-promoted allenylstannane
reaction with aldehyde (S)-3b which gives the analogous
(R ) Bn) diastereomeric adducts as an 84:16 mixture.1
J . Org. Chem., Vol. 65, No. 2, 2000 631
and anti,syn adducts 11 and 12 after treatment of the
crude vinyl chloride adducts with TBAF in THF (eq 8).
The latter isomer afforded crystals suitable for X-ray
structure analysis.11
The “mismatched” pairing of allenylsilane (P)-2b with
the benzyloxy aldehyde (R)-3b and subsequent dechlo-
rosilation of the adduct with TBAF afforded the syn,anti
adduct 13 as the sole product (eq 9). The analogous
addition of (M)-2b to aldehyde (R)-3b led to the anti,anti
adduct 14 (eq 10). The structure of this product was
confirmed by spectral comparison with an authentic
sample.12
The R-Me, â-OBn aldehydes (S)- and (R)-3b gave
remarkably different results from their ODPS counter-
parts. Addition of allenylsilane (M)-2a to (S)-3b, a
presumably mismatched pairing, yielded the syn,anti
product as the sole adduct (eq 5). Moreover, the matched
pairing of silane (M)-2a and aldehyde (R)-3b afforded the
anti,anti adduct 7 (eq 6)! The stereochemistry of these
adducts was assigned by comparison with authentic
samples prepared by allenylstannane additions to alde-
hyde (R)-3b.1
Whereas additions of the allenylsilanes 2a and 2b to
the ODPS aldehydes (R)- and (S)-3a closely parallel BF3-
promoted additions of the analogous allenylstannanes,
the results with the OBn aldehydes (R)- and (S)-3b are
strikingly different. Allenylsilane (M)-2a affords the
syn,anti adduct 5b with (S)-3b and the anti,anti adduct
7 with (R)-3b as the exclusive products. Silanes (P)- and
(M)-2b show analogous behavior with aldehyde (R)-3b.
By comparison, the (P)-stannane counterpart of allenyl-
silane 2a affords an 84:16 mixture of syn,anti and
anti,syn adducts (mismatched) and the (M)-stannane
gives the syn,syn isomer (matched) as the sole adduct
with aldehyde (R)-3b.1
A possible explanation for these results is depicted in
Figure 1. The matched pairings of the â-ODPS aldehyde
(R)-3a with allenylsilanes (M)-2a and 2b proceed through
the acyclic antiperiplanar Felkin-Anh transition state
A. The mismatched addition to aldehyde (S)-3a favors
either the anti-Felkin-Anh antiperiplanar arrangement
B or, quite possibly, a chelation arrangement comparable
to D.13 The minor mismatched anti,syn adducts would
be formed via the synclinal Felkin-Anh arrangement C.
The reactions that proceed by way of acyclic transition
An analogous series of experiments was carried out
with allenylsilane 2b. Addition of (M)-2b to aldehyde (R)-
3a , a matched pairing, afforded the syn,syn vinyl chloride
8 (eq 7). This product results from attack on an incipient
vinyl cation by chloride, a process previously noted by
Danheiser for additions of trimethylsilylallene to alde-
hydes promoted by TiCl4.5 Cleavage of the DPS ether with
aqueous HCl afforded the crystalline alcohol 9 whose
structure was confirmed through X-ray analysis.11 Treat-
ment of this alcohol, or the DPS ether 8 with TBAF in
THF effected dechlorosilation to the syn,syn-diol 10, also
a crystalline solid amenable to X-ray structure analysis.11
Cleavage of the aforementioned TMS-substituted vinylic
chloride was effected with KF in DMSO, by Danheiser.5
(11) This analysis was performed by Dr. Michael Sabat of this
department.
(12) The authentic sample was prepared by Dr. Brian J ohns
according to the following sequence.3
The mismatched addition of allenylsilane (P)-2b to
aldehyde (R)-3a yielded an 80:20 mixture of the syn,anti

632 J . Org. Chem., Vol. 65, No. 2, 2000
Notes
(250 mg, 33.7 mg atom) were added. The mixture was stirred
for 12 h at room temperature. The resulting red/brown solution
was transferred by cannula into a slurry of CuCN (305 mg, 3.4
mmol) in THF (12 mL) at 0 °C. The mixture was stirred for 30
min then cooled to -78 °C. To mesylate 1b (500 mg, 3.37 mmol)
in THF (25 mL) at -78 °C was added the silyl cuprate via
cannula. The reaction mixture was stirred at -78 °C for 3 h
and then poured into a mixture of 9:1 NH4Cl/NH4OH and stirred
until the black emulsion disappeared to leave a bright blue
aqueous layer. The product was extracted with pentane and
dried, and the solvent was removed under aspirator vacuum to
yield a colorless liquid that was distilled under reduced pressure
(100 °C at 20 Torr) to afford 430 mg (70%) of allene (M)-2b: IR
(neat) 1938 cm-1; 1H NMR (300 MHz, CDCl3) 7.54 (m, 2H), 7.35
(m, 3H), 5.01 (m, 1H), 4.80 (p, J ) 6.9 Hz, 1H), 1.63 (m, 3H),
0.34 (s, 6H); 13C NMR (75 MHz, CDCl3) 191.0 133.8, 129.0, 128.4,
127.7, 80.4, 78.4, 13.1, -2.3; [R]20 ) +53.0 (c ) 2.6, CH2Cl2).
D
Anal. Calcd for C12H16Si: C, 76.53; H, 8.56. Found: C, 76.47;
H, 8.70.
(R)-4-(Dim eth yl)p h en ylsilyl-2,3-h exa d ien e [(M)-2a ]. The
procedure for the synthesis of allene (M)-2b was followed with
(dimethyl)phenylchlorosilane (775 mg, 4.50 mmol) in THF (4 mL)
containing 4 Å molecular sieves and Li wire (160 mg, 22.7 mg
atom), CuCN (203 mg, 2.30 mmol), and mesylate 1a (400 mg,
2.30 mmol). The product was extracted with pentane and dried,
and the solvent was removed under aspirator vacuum to yield
a colorless liquid that was purified on silica gel (1:20 EtOAc/
hexanes) affording 300 mg (61%) of allenylsilane (M)-2a : IR
2968, 2916, 1938 cm-1; 1H NMR (300 MHz, CDCl3) 7.52 (m, 2H),
7.35 (m, 3H), 4.86 (m, 1H), 1.92 (dq, J ) 3.3, 7.5 Hz, 2H), 1.63
(d, J ) 6.6 Hz, 3H), 0.98 (t, J ) 7.5 Hz, 3H), 0.35 (s, 6H); 13C
NMR (75 MHz, CDCl3) 207.3, 139.0, 133.8, 129, 127.6, 96.3, 81.1,
22.5, 13.9 13.6, -2.87; [R]20D ) -23 (c ) 1.0, CH2Cl2). Anal. Calcd
for C14H20Si: C, 77.71; H, 9.32. Found: C, 77.47; H, 9.48.
Ad d it ion of Allen ylsila n es (M)-2 t o Ald eh yd e (R)-3b .
P r oced u r e A: (2R,3S,4S)-1-Ben zyloxy-2,4-d im eth yl-5-oc-
tyn -3-ol (7). Aldehyde (R)-3b (32 mg, 0.18 mmol) and allene
(M)-2a (50 mg, 0.27 mmol) were dissolved in CH2Cl2 (1.0 mL)
and cooled to -78 °C. TiCl4 (0.20 mL of 1 M in hexanes, 0.20
mmol) was added to the mixture with stirring until TLC analysis
showed complete consumption of the aldehyde (∼30 min). NH4-
Cl (aq) was added, and the reaction mixture was allowed to
warm to room temperature. The mixture was poured into CH2-
Cl2, the layers were separated, and the organic portion was
washed with NaHCO3 (aq). The organic phase was then dried
(MgSO4) and the solvent removed under aspirator vacuum. The
product was purified on silica gel (1:9 EtOAc/hexanes) to yield
32 mg (70%) of the anti,anti alcohol 7:1 1H NMR (300 MHz,
CDCl3) 7.33 (m, 5H), 4.52 (s, 2H), 3.68-3.57 (m, 4H), 3.28 (m,
1H), 3.06 (bs, 1H), 2.67 (m, 1H), 2.19 (dq, J ) 6.0, 2.1 Hz, 2H),
2.11 (m, 1H), 1.24 (d, J ) 6.9 Hz, 3H), 1.13 (t, J ) 6.0 Hz, 3H),
0.93 (d, J ) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) 128.4, 127.6,
F igu r e 1. Proposed transition states for TiCl4-promoted
additions of allenylsilanes to R-methyl â-oxygenated aldehydes.
states are reagent controlled. Additions to the â-OBn
aldehydes (S)- and (R)-3b, on the other hand, proceed
via the chelated transition states D and E. In these
additions the chelated aldehyde strongly directs the
approach of the allenylsilane reagent (substrate control).
In contrast, the analogous MgBr2-promoted addition of
the allenylstannane corresponding to (M)-2a affords a 1:1
mixture of the syn,syn and anti,anti adducts with alde-
hyde (R)-3b.1 Evidently, TiCl4 is a more effective chelat-
ing Lewis acid than MgBr2.
The present studies show that the TiCl4-promoted
reaction of allenylsilanes with R-methyl-â-oxygenated
aldehydes can be utilized to synthesis syn,syn and
syn,anti adducts of possible use for polyketide synthesis.
The additions proceed without epimerization of R-chiral
aldehydes. However, some care must be exercised in the
choice of a â-oxygen substituent. We have found that
OTBS groups are desilylated to a large extent under
these reaction conditions. p-Methoxybenzyl ethers are
also extensively cleaved.
78.14, 74.62, 73.38, 37.60; 30.31, 18.42, 14.09; [R]20 +3.55 (c )
D
0.60, CH2Cl2).
P r oced u r e B: (2R,3S,4S)-1-Ben zyloxy-2,4-d im eth yl-5-
h exyn -3-ol (14). Aldehyde (R)-3b (570 mg, 3.03 mmol) and
allene (M)-2b (340 mg, 4.55 mmol) were dissolved in CH2Cl2 (8.0
mL) and cooled to -78 °C. TiCl4 (2.25 mL of 1 M in hexanes,
2.25 mmol) was added dropwise to the mixture with stirring
until TLC analysis showed complete consumption of the alde-
hyde (∼30 min). NH4Cl (aq) was added, and the reaction mixture
was allowed to warm to room temperature. The mixture was
poured into CH2Cl2, the layers were separated, and the organic
portion was washed with NaHCO3 (aq). The organic phase was
then dried (MgSO4) and the solvent removed under aspirator
vacuum. The resulting oil was dissolved in THF, and TBAF (5
mL of 1 M in THF) was added at room temperature. The reaction
was allowed to stir for 15 min. It was then poured into water,
and the product was extracted with ether. The organic extracts
were combined and dried (MgSO4), and the solvent was removed
under aspirator vacuum to yield a colorless oil. The product was
chromatographed on silica gel (1:9 EtOAc/hexanes) to remove
the unreacted allene and the silicon byproducts affording 381
mg (86%) of the anti,anti alcohol 14: 1H NMR (300 MHz, CDCl3)
7.4-7.26 (m, 5H), 4.53 (s, 2H), 3.63 (A of ABX, J AX ) 4.50 Hz,
J AB ) 9.0 Hz, 1H), 3.55 (B of ABX, J BX ) 8.1 Hz, J AB ) 9.0 Hz,
1H), 3.46 (bs, 1H), 3.36 (dd, J ) 3.0, 8.4 Hz, 1H), 2.70 (m, 1H),
Exp er im en ta l Section
(S)-1-(Dim eth yl)p h en ylsilyl-1,2-bu ta d ien e [(M)-2b]. The
procedure is a modification of methodology published by Flem-
ing.7 (Dimethyl)phenylchlorosilane (1.15 g, 6.70 mmol) was
dissolved in THF (6 mL), and 4 Å molecular sieves and Li wire
(13) Recent work with methylaluminum halide Lewis acids has
shown that additions to â-OTBS aldehydes can proceed by chelation-
controlled transition states. Evans, D. A.; Allison, B. D.; Yang, M. G.
Tetrahedron Lett. 1999, 40, 4457. Evans, D. A.; Halstead, D. P.; Allison,
B. D. Tetrahedron Lett. 1999, 40, 4461.

Notes
J . Org. Chem., Vol. 65, No. 2, 2000 633
2.14 (m, 1H), 2.1 (d, J ) 2.4 Hz, 1H), 1.3 (d, J ) 7.2 Hz, 3H),
0.93 (d, J ) 6.9 Hz, 3H);. 13C NMR (75 MHz, CDCl3) 133, 128,
mmol) was dissolved in methanol (15 mL) and 5% HCl was
added at 0 °C. The reaction mixture was stirred at room
temperature overnight and poured into NaHCO3 (aq), and the
product was extracted into ether. The organic extract was dried
(MgSO4), and the solvent was removed under aspirator vacuum
to yield diol 9, which was purified on silica gel (1:9 EtOAc/
hexanes) to remove the silyl byproducts affording 53 mg (70%)
of a white solid. Crystallization from hexane afforded an X-ray
quality crystal: 1H NMR (300 MHz, CDCl3) 7.54-7.26 (m, 5H),
5.81 (s, 1H), 3.91 (d, J ) 8.7 Hz, 1H), 3.69 (A of ABX, J AX ) 3.9
127.8, 127.6, 78.1, 74.9, 73.4, 70.3, 37.3, 30.1, 17.9, 13.8; [R]20
D
) -13.24 (c ) 1.32, CH2Cl2).
(2R,3R,4S)-1-(ter t-Bu tyld ip h en ylsilyl)oxy-2,4-d im eth yl-
5-octyn -3-ol (4). Procedure A described above was employed.
Aldehyde (R)-2b (100 mg, 0.31 mmol) and allene (M)-2a (100
mg, 0.365 mmol) were dissolved in CH2Cl2 (1.0 mL), and TiCl4
(340 µL of 1 M in hexanes) was added at -78 °C. The mixture
was stirred until TLC analysis showed complete consumption
of the aldehyde (∼30 min). The product was purified on silica
gel (1:9 EtOAc/hexanes) to remove the unreacted allene and the
silicon byproducts affording 110 mg (70%) of the syn,syn alcohol
4: IR 3510, 2963, 2931, 1728 cm-1; 1H NMR (300 MHz, CDCl3)
Hz, J AB ) 10.8 Hz, 1H), 3.58 (B of ABX, J BX ) 5.1 Hz, J AB
)
10.2 Hz, 1H), 2.6 (m, 2H), 1.75 (m, 1H), 1.13 (d, J ) 6.3 Hz,
3H), 0.72 (d, J ) 6.6 Hz, 3H), 0.43 (d, J ) 4.2, 6H); 13C NMR (75
MHz, CDCl3) 133.7, 129.5, 128.0, 126.5, 15.9, 68.0, 45.1, 36.5,
29.3, 28.9, 16.3, 8.9, -1.15; MS m/z 313, 277, 235, 223, 107.
(2R,3R,4S)-5-Hexyn e-1,3-d iol (10). ProcedureB described
above was employed. Aldehyde (R)-3a (72 mg, 0.303 mmol) and
allene (M)-2b (100 mg, 0.255 mmol) were combined in CH2Cl2
(1.0 mL), and TiCl4 (300 µL of 1 M in hexanes) was added at
-78 °C. The mixture was stirred until TLC analysis showed
complete consumption of the aldehyde (∼30 min). The resulting
oil was dissolved in THF and TBAF (765 µL of 1 M in THF) was
added. The product was purified on silica gel (1:5 EtOAc/
hexanes) to remove the unreacted allene and the silicon byprod-
ucts affording 25 mg (70%) of the syn,syn diol 10: 1H NMR (300
MHz, CDCl3) 3.82-3.65 (m, 3H), 2.55 (m, 1H), 2.45 (bs, 2H),
2.2 (m, 1H), 2.08 (d, J ) 2.7 Hz, 1H), 1.29 (d, J ) 6.9 Hz, 3H),
0.984 (d, J ) 6.9 Hz, 3H); [R]20D ) -13.5 (c ) 2.5, CH2Cl2). Anal.
Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.46; H, 9.95.
(2R,3S,4R)-1-Ben zyloxy-2,4-d im eth yl-5-h exyn -3-ol (13).
Procedure B described above was employed. Aldehyde (R)-3b
(100 mg, 0.56 mmol) and allene (P)-2b (158 mg, 0.84 mmol) were
dissolved in CH2Cl2 (2.0 mL), and TiCl4 (620 µL of 1 M in
hexanes) was added. The mixture was stirred until TLC analysis
showed complete consumption of the aldehyde (∼30 min). The
resulting oil was dissolved in THF and TBAF (765 µL of 1 M in
THF). The product was purified on silica gel (1:9 EtOAc/hexanes)
to remove unreacted allene and silicon byproducts affording 75
mg (60%) of the syn,anti alcohol 13: IR 3370, 3301, 2968, 2357,
7.70-7.66 (m, 6H), 7.42-7.33 (m, 4H), 3.84 (A of ABX, J AX
)
3.3 Hz, J AB ) 9.9 Hz, 1H), 3.70 (m, 2H), 3.11 (m, 1H), 2.51 (m,
1H), 2.18 (m, 1H), 2.13 (dq, J ) 2.1, 7.8 Hz, 2H) 1.26 (d, 3H, J
) 6.9 Hz), 1.08 (t, J ) 7.5 Hz, 3H), 1.07 (m, 12H), 1.01 (d, J )
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) 135.7, 135.5, 129.8,
127.74, 83.53, 81.18, 78.08, 69.6, 36.7, 30.34, 26.8, 19.16, 18.05,
14.26, 12.36, 9.56; [R]20 ) -4.0 (c ) 1.0, CH2Cl2).
D
(2S,3R,4S)-1-Ben zyloxy-2,4-d im et h yl-5-oct yn -3-ol (5b ).
Procedure A described above was employed. Aldehyde (S)-3b (32
mg, 0.31 mmol) and allene (M)-2a (50 mg, 0.365 mmol) were
dissolved in CH2Cl2 (1.0 mL), and TiCl4 (195 µL of 1 M in
hexanes) was added at -78 °C. The mixture was stirred until
TLC analysis showed complete consumption of the aldehyde
(∼30 min). The product was purified on silica gel (1:9 EtOAc/
hexanes) to remove unreacted allene and silicon byproducts to
yield 32 mg (70%) of the syn,anti alcohol 5b: IR 3493, 2960,
1737 cm-1 1H NMR (300 MHz, CDCl3) 7.32 (m, 5H), 4.51 (s,
;
2H), 3.75 (A of ABX, J AX ) 4.2 Hz, J AB ) 9.3 Hz, 1H), 3.54 (B of
ABX, J BX ) 4.5 Hz, J AB ) 9.3 Hz, 1H), 3.42 (dd, J ) 6.0, 12.0
Hz, 1H), 3.06 (d, J ) 5.7 Hz, 1H), 2.54 (m, 1H), 2.15 (dq, J )
2.1, 7.8 Hz, 2H), 2.14 (m, 1H), 1.20 (d, J ) 6.9 Hz, 3H), 1.1 (t, J
) 7.5 Hz, 3H), 1.07 (d, J ) 6.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3) 137.9, 128.4, 127.7, 127.5, 83.4, 81.6, 78.6, 73.5, 35.3,
30.9, 29.7, 16.4,15.0, 14.2, 12.4; [R]20D ) -20.1 (c )1.2, CH2Cl2).
Reported for ent-5b [R]D ) +20.8 (c ) 0.53, CHCl3 ).1
2113 cm-1 1H NMR (300 MHz, CDCl3) 7.33 (m, 5H), 4.51 (s,
;
(E,2R,3R,4R)-5-Ch lor o-2,4-d im eth yl-6-(d im eth yl)p h en yl-
silyl-1-(ter t-bu tyld ip h en ylsilyl)oxy-5-h exen -3-ol (8). A solu-
tion of aldehyde (R)-3a (100 mg, 0.303 mmol) and allene (M)-2b
(90 mg, 0.455 mmol) in CH2Cl2 (1.0 mL) was cooled to -78 °C,
and then TiCl4 (280 µL of 1 M in hexanes) was added dropwise.
The mixture was stirred until TLC analysis showed complete
consumption of the aldehyde (∼30 min). NH4Cl (aq) was added,
and the reaction was allowed to warm to room temperature. The
mixture was poured into CH2Cl2, the layers were separated, and
the organic portion was washed with NaHCO3 (aq). The organic
phase was then dried (MgSO4), and the solvent was removed
under aspirator vacuum. The product was purified on silica gel
(1:20 EtOAc/hexanes) to afford unreacted allene and 125 mg
2H), 3.77 (dd, J ) 3.6, 9.0 Hz, 1H), 3.50 (m, 2H), 3.26 (d, 1H),
2.57 (ddq, J ) 2.4, 6.6, 6.6 Hz, 1H), 2.16 (m, 1H), 2.08 (d, J )
3.0 Hz, 1H), 1.26 (d, J ) 6.9 Hz, 3H), 1.07 (d, J ) 6.9 Hz, 3H);
13C NMR (75 MHz, CDCl3) 137.65, 128.41, 127.75, 127.61, 86.83,
78.39, 73.57, 69.68, 35.12, 30.61, 15.92, 14.97; [R]20 ) +18.78
D
(c ) 1.65, CH2Cl2).
Ack n ow led gm en t. This work was supported by
Research Grant CHE9525974 from the National Science
Foundation. We are grateful to Dr. Michal Sabat for
helpful assistance in the selection of crystals and for
performing the X-ray structure analyses.
(80%) of the vinyl chloride 8: IR(neat) 3467, 2960, 2934 cm-1
;
1H NMR (300 MHz, CDCl3) 7.64-7.34 (m, 15H), 5.78 (s, 1H),
3.97 (d, J ) 8.4 Hz, 1H), 3.74 (dd, J ) 9.9, 3.6 Hz, 1H), 3.56 (dd,
J ) 9.75, 5.1 Hz, 1H), 2.6 (m, 2H), 1.75 (m, 1H), 1.16 (d, J ) 6.3
Hz, 3H), 1.05 (s, 9H), 0.70 (d, J ) 6.6 Hz, 3H), 0.43 (d, J ) 4.2
Hz, 6H).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for adducts 5a /6 and 11/12, 1H NMR spectra for all
products, and ORTEP diagrams for 9, 10, and 12.This material
is available free of charge via the Internet at http://pubs.acs.org.
(E,2R,3R,4R)-5-Ch lor o-2,4-d im eth yl-6-(d im eth yl)p h en yl-
silyl-5-h exen e-1,3-d iol (9). The vinyl chloride 8 (125 mg, 0.24
J O991543Y