Addition of allenylzinc reagents, prepared in situ from nonracemic propargylic mesylates, to aldehydes. A new synthesis of highly enantioenriched homopropargylic alcohols

Article abstract of DOI:10.1021/jo9823083

Enantioenriched propargylic mesylates are converted to chiral allenylzinc reagents via transient allenylpalladium species by treatment with a Pd(0)-phosphine catalyst in the presence of excess Et₂Zn. These zinc reagents undergo S(E)2' additions to various aldehydes to yield mainly the anti homopropargylic alcohol adducts of high ee. The reaction is most efficient in THF with Pd(OAc)₂· PPh₃ as the catalyst precursor. As little as 2.5 mol % of this precursor is effective.

Full text of DOI:10.1021/jo9823083

J . Org. Chem. 1999, 64, 5201-5204
5201
Ad d ition of Allen ylzin c Rea gen ts, P r ep a r ed in Situ fr om
Non r a cem ic P r op a r gylic Mesyla tes, to Ald eh yd es. A New Syn th esis
of High ly En a n tioen r ich ed Hom op r op a r gylic Alcoh ols
J ames A. Marshall* and Nicholas D. Adams
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901
Received November 23, 1998
Enantioenriched propargylic mesylates are converted to chiral allenylzinc reagents via transient
allenylpalladium species by treatment with a Pd(0)-phosphine catalyst in the presence of excess
Et2Zn. These zinc reagents undergo SE2′ additions to various aldehydes to yield mainly the anti
homopropargylic alcohol adducts of high ee. The reaction is most efficient in THF with Pd(OAc)2‚
PPh3 as the catalyst precursor. As little as 2.5 mol % of this precursor is effective.
We recently described a method for preparing non-
racemic homopropargylic alcohols II from propargylic
mesylates I and aldehydes by metal exchange of a
presumed allenylpalladium species with diethylzinc (eq
1).1 The impetus for these studies came from several
F igu r e 1. Possible catalytic cycle for Pd(0) catalyzed zincation
of propargylic mesylates.
earlier reports by Tamaru and co-workers, who employed
racemic allylic and propargylic esters and halides for
analogous additions leading to homoallylic and homopro-
pargylic alcohols.2 Tamaru’s studies were carried out on
benzaldehyde and achiral or racemic propargylic esters.
The homopropargylic adducts derived from 3-butyn-2-yl
benzoate, methyl carbonate, bromide, and tosylate were
formed as 1:1 mixtures of syn and anti isomers. In
contrast, we found that enantioenriched 3-butyn-2-ol
mesylates react under the Tamaru conditions with
aliphatic aldehydes to form mainly anti adducts of high
ee.
The high stereoselectivity of additions to branched
aldehydes was of particular interest to us in connection
with our work on the synthesis of polypropionate natural
products.3 Our proposed catalytic cycle for the metal
exchange process (Figure 1) is based on evidence from
the Tamaru group, who isolated the product of â-hydride
elimination (benzyl acrylate) from reactions in which
benzyl â-iodozincopropionate served as the source of
zinc.2d Additional evidence comes from the work of
Knochel and co-workers, who reported the rapid decom-
position of Et2PdLn2 to ethylene and ethane with regen-
eration of the Pd(0) catalyst.4
Our initial results, though promising, had several
shortcomings. (1) Yields were not uniformly high. (2) A
2-fold excess of the mesylate was required. (3) Low
concentrations of reactants (∼0.05 M) were necessary to
minimize addition of an ethyl group from the diethylzinc
to the aldehyde. In an effort to rectify at least some of
these shortcomings, a more systematic study of the
reaction was carried out. Several solvents were examined,
including benzene, toluene, hexane, CH2Cl2, DME, and
THF. Of these, THF was clearly superior. No reaction
took place in the hydrocarbon solvents, and only slow
product formation was observed in CH2Cl2 and DME. The
use of as much as 10 equiv of Et2Zn did not increase the
yield, and increased concentrations of reactants led to
significant amounts (∼50% at 0.1 M) of ethylated alde-
hyde resulting in reduced yields of propargylic adducts.
(1) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1998, 63, 3812.
(2) (a) Shimizu, M.; Kimura, M.; Tanaka, S.; Tamaru, Y. Tetrahedron
Lett. 1998, 39, 609. (b) Tamaru, Y.; Goto, S.; Tanaka, A.; Shimizu, M.
Angew. Chem., Int. Ed. Engl. 1996, 35, 878. (c) Tamaru, Y.; Tanaka,
A.; Yasui, K.; Goto, S.; Tanaka, S. Angew Chem., Int. Ed. Engl. 1995,
34, 787. (d) Yasui, K.; Goto, Y.; Takafumi, Y.; Taniseki, Y.; Fugami,
K.; Tanaka, A.; Tamaru, Y. Tetrahedron Lett. 1993, 34, 7619.
(3) For a recent application, see: Marshall, J . A.; J ohns, B. A. J .
Org. Chem. 1998, 63, 7885.
(4) Stadtmuller, H.; Lentz, R.; Tucker, C. T.; Studmann, T.; Dorner,
W.; Knochel, P. J . Am. Chem. Soc. 1993, 115, 7027.
10.1021/jo9823083 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/16/1999

5202 J . Org. Chem., Vol. 64, No. 14, 1999
Marshall and Adams
Ta ble 1. Effect of Ca ta lyst on th e Allen ylozin c Ad d ition
Ta ble 2. Effect of Tem p er a tu r e a n d Con cen tr a tion on
th e Allen ylzin c Ad d ition t
Pd(0)
t, h
T, °C 1, equiv concn, M yield,a
%
concn, M
T, °C
t, h
yield,a,b
%
Pd (PPh3)4
Pd (MeCN)2Cl2
Pd(dppf)Cl2
3
2
0
0
2.0
1.5
2.0
1.5
1.5
1.5
0.05
0.05
0.05
0.1
51
dec
37
0.1
0.2
0.1
0.2
0.1
-78
-78
-50
-30
-20
4
4
36
1.5
12
0
0
36
50
75
36 0 to rt
b
Pd(OAc)2‚PPh3
12 -20
2
2
75
PdCl2‚2PPh3
0
0.05
0.05
74
58
Pd(OAc)2‚2PPh3
0 to rt
a
b
a
b
∼95:5 anti/syn. 2.5 mol % catalyst.
The product is racemic. A 95:5 mixture of anti and syn
adducts.
The effect of Pd catalyst was next examined. These
studies employed a number of commonly available cata-
lyst precursors5 with racemic propargylic mesylate 1a
and cyclohexanecarboxaldehyde in THF (Table 1). Addi-
tions utilizing Pd(PPh3)4 as the catalyst produced the anti
adduct 3a in 51% yield with a small amount (<5%) of
the syn adduct as a minor product. The use of Pd-
(MeCN)2Cl2 caused rapid decomposition of the mesylate.
Pd(dppf)Cl2 was moderately effective but offered no
advantages over Pd(PPh3)4.
Ta ble 3. Ad d ition s of th e Allen ylzin c Rea gen t Der ived
fr om Mesyla te (R)-1a to Ach ir a l Ald eh yd es
A report by Oppolzer on the use of Pd(OAc)2‚PBu3 for
an intramolecular metalloene reaction involving an allylic
Pd-Zn metathesis prompted our interest in this catalyst
precursor.6 However, we experienced difficulties obtain-
ing Bu3P of sufficient purity. For this reason, we decided
to substitute Ph3P.7 This combination showed a marked
improvement over the previously examined catalysts. The
reaction proceeded in 75% yield, and it could be carried
out at -20 °C with only a 30% excess of mesylate.
Moreover, a reactant concentration of 0.1 M did not lead
to ethylated aldehyde, and as little as 2.5 mol % of
catalyst was effective. We also found that PdCl2‚2PPh3
could be employed with comparable results. Surprisingly,
Pd(OAc)2‚2PPh3 was significantly less effective than the
analogous chloride or the 1:1 complex. Control experi-
ments in which the Pd(0) catalyst or the Et2Zn were
omitted from the reaction afforded only recovered start-
ing materials. None of the adduct 3a was detected.
A more systematic examination of reaction concentra-
tion and temperature was conducted with Pd(OAc)2‚PPh3
(Table 2). At -78 °C, no products were observed within
a reasonable time. However, at -20 to -30 °C, adduct
formation was relatively efficient and higher concentra-
tions of reactants could be employed with minimal
production of byproducts.
R
yield,a
%
anti/syn
ee,b %
c-C6H11 (2a )
C6H13 (2b)
75 (51)
74 (57)
75 (47)
65 (57)
95:5
88:12
95:5
90 (3a )
86 (3b)
92 (3c)
nd (3d )c
i-Pr (2c)
(E)-BuCHdCH (2d )
72:28
a
Yields in parentheses are for reactions in which 5 mol %
Pd(PPh3)4 was employed as the catalyst. b For the anti isomer.c Not
determined.
allenylzinc intermediate V with the initially formed
allenylpalladium species III (Figure 1). This suspicion
was confirmed upon treatment of the racemic propargylic
mesylate 4 with Pd(PPh3)4 and Et2Zn in THF without
added aldehyde (eq 2). This reaction proceeded signifi-
cantly slower at -20 °C than those in which aldehyde
was present. However, at room temperature, a mixture
of the ethylated allene 5 (33%) and the diallene 6 (10%),
a 1:1 mixture of diastereomers, was produced in 2 h.
Negligible amounts of these materials were formed in
reactions employing Pd(OAc)2‚PPh3.
As a first test of the improved allenylzinc methodology,
we performed additions of the reagent derived from
enantioenriched mesylate (R)-1a to representative achiral
aldehydes 2a -d with 3 equiv of Et2Zn (Table 3). The
results of these additions parallel our previous findings
with the Pd(PPh3)4 catalyst, but the yields of adducts are
significantly higher.1 These higher yields are realized
with considerably less chiral mesylate than previously
employed. The diastereoselectivity and product ee are
comparable.
We detected small amounts of ethylated allenic byprod-
uct in the reactions of Table 1, especially with Pd(PPh3)4
as the catalyst. In addition, a trace amount of at least
one other allenic byproduct was produced in quantities
too small for characterization. We suspected this to be
an allenic dimer formed by coupling of the transient
(5) Tsuji, J . Palladium Reagents and Catalysts; J ohn Wiley and
Sons: Chinchester, 1995; pp 1-5.
(6) Oppolzer, W.; Flachsmann, F. Tetrahedron Lett. 1998, 39, 5019.
Mandai, T.; Matsumoto, T.; Tsuji, J .; Saito, S. Tetrahedron Lett. 1993,
34, 2513.
(7) This combination has not previously been utilized. For a discus-
sion of possible catalytically active species, see ref 5, p 2, and the
following cited reference: Amatore, C.; J utand, A.; M’Barki, M. A.
Organometallics 1992, 11, 3009.

Addition of Allenylzinc Reagents to Aldehydes
J . Org. Chem., Vol. 64, No. 14, 1999 5203
We next examined additions of the reagents derived
from the enantioenriched mesylates (R)-1a and (R)-1b1
(>95% ee) to the R-methyl-â-ODPS aldehydes (S)- and
(R)-7 (eqs 3 and 4).9 The anti,syn adducts 8 and 9 were
obtained in 72 and 70% yield from the former aldehyde
(eq 3), and the anti,anti adducts 10 and 11 were produced
in comparable yield from the latter (eq 4).10
F igu r e 2. Possible cyclic transition states for allenylzinc
additions to aldehydes (S)-7 and (R)-7.
product accompanying adduct 13 in eq 5 was not isolated
in quantities sufficient for structure determination.
The formation of mainly anti adducts is suggestive of
a cyclic transition state for the additions. One possible
scenario is depicted in Figure 2 in which adducts 8 and
9 arise via a Felkin-Ahn orientation (F -A), whereas 10
and 11 are formed through an anti Felkin-Ahn (AF -
A), or less likely, a chelation-controlled arrangement.9,13
The trace amounts of inseparable isomeric products
detected in these reactions are presumed to be syn
adducts. The reactions leading to adducts 13 and 14 can
be viewed in a similar light.
A further test of double diastereoselection is provided
by the reaction of aldehyde 1210 and the allenylzinc
reagents from mesylates (R)-1a and (S)-1a (eqs 5 and 6).
To illustrate a possible application of this methodology,
we converted the homopropargylic alcohols 9 and 11 to
the unsaturated lactones (pentenolides) 17 and 20 through
carboxylation of the lithiated alkynes with CO2 followed
by partial hydrogenation of the triple bond14 and thermal
lactonization (eq 7). The 4-alkylpentenolide moiety of 17
and 20 is found in a number of biologically active
polypropionate natural products.15
The present modifications represent significant im-
provements in the additions of in situ generated chiral
allenylzinc reagents to aldehydes. The high degree of
reagent control in additions to aldehydes 7 and 12 is
especially noteworthy. In view of the ready availability
of the precursor propargylic alcohols,16 and given the ease
of performing the addition reactions, the methodology
should find widespread applications for the synthesis of
highly enantioenriched homopropargylic alcohols.3
These additions both proceeded in ca. 70% yield. Adduct
13 was produced as the major isomer of a separable
mixture (>15:1) of stereoisomers. Adduct 14 was formed
as a similar mixture. The structures of these adducts are
assigned by analogy. In the latter reaction, the minor
product was adduct 13, which most likely arises as a
consequence of partial racemization of the allenylpalla-
dium precursor of the allenylzinc reagent.12 The minor
(13) The transition states depicted in Figure 2 are illustrative only.
It is possible that Et2Zn complexes may also participate as shown by
Noyori and others in amine-catalyzed additions of dialkylzinc com-
pounds to aldehydes. Cf. Noyori, R.; Kitamura, M. Angew. Chem., Int.
Ed. Engl. 1991, 30, 49. Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833.
Rijenberg, E.; Neldes, J . H.; Kleij, A. W.; J astrzebski, J . T. B. H.;
Boersma, J .; J anssen, M. D.; Spek, A. L.; van Koten, G. Organome-
tallics 1997, 16, 2847. Allylic zinc halides add without catalysis to
aldehydes with allylic inversion as expected for SE2′ additions. Yama-
moto, Y.; Asao, N. Chem. Rev. 1993, 93, 7. On the basis of other
allenylmetal additions, we believe that the allyl analogy is appropriate.
However, it should be noted that, under Barbier conditions, crotylzinc
halides afford nearly 1:1 mixtures of anti and syn adducts, implying a
rather loose transition state.
(14) Adams, M. A.; Duggan, A. J .; Smolanoff, J .; Meinwald, J . J .
Am. Chem. Soc. 1979, 101, 5364.
(15) Kobayashi, M.; Wang, W.; Tsutsui, Y.; Sugimoto, M.; Mu-
rakama, N. Tetrahedron Lett. 1998, 39, 8291.
(16) Yadev, J . S.; Chandler, M. C.; Rao, C. S. Tetrahedron Lett. 1989,
30, 5455. Marshall, J . A.; J iang, H. Tetrahedron Lett. 1998, 39, 1493.
Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J . Am. Chem.
Soc. 1997, 119, 8738.
(8) Roush, W. R.; Palkowitz, A. D.; Palmer, M. A. J . Org. Chem.
1987, 52, 316.
(9) Marshall, J . A.; Perkins, J . F.; Wolf, M. A. J . Org. Chem. 1996,
60, 5556. Marshall, J . A.; Palovich, M. R. J . Org. Chem. 1997, 62, 6001.
(10) Aldehyde 12 was first prepared by Brian J ohns in our labora-
tory through condensation of hydrocinnamaldehyde with the Evans
propionyl oxazolidinone derived from norephedrine.11 Full details are
provided in the Supporting Information.
(11) Evans, D. A.; Mathre, D. J .; Scott, W. L. J . Org. Chem. 1985,
50, 1830. Cf. Brimble, M. A. Aust. J . Chem. 1990, 43, 1035.
(12) Marshall, J . A.; Wolf, M. A. J . Org. Chem. 1996, 61, 3238.

5204 J . Org. Chem., Vol. 64, No. 14, 1999
Marshall and Adams
1.17, CHCl3); IR (film) ν 3491, 2240, 1747 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.71-7.64 (m, 4H), 7.48-7.36 (m, 6H), 4.69
(d, J ) 1.8 Hz, 2H), 3.80-3.66 (m, 2H), 3.43 (m, 2H), 2.74 (m,
1H), 2.08 (s, 3H), 2.01 (m, 1H), 1.30 (d, J ) 6.9 Hz, 3H), 1.06
(s, 9H), 0.83 (d, J ) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
170.2, 135.5, 132.9, 129.8, 127.7, 87.8, 78.1, 76.1, 68.3, 52.7,
38.9, 30.4, 26.7, 20.7, 19.0, 17.6, 13.5. Anal. Calcd for C27H36O4-
Si: C, 71.64; H, 8.02. Found: C, 71.41; H, 8.05.
a n ti,a n ti,syn -Alcoh ol 14. The standard procedure was
employed with Pd(OAc)2 (2.7 mg, 0.012 mmol), PPh3 (3.1 mg,
0.012 mmol), mesylate (S)-1a (81 mg, 0.37 mmol), aldehyde
12 (75 mg, 0.24 mmol), and diethylzinc (0.74 mL, 1 M in
hexane, 0.74 mmol) in THF (1.8 mL) at -20 °C for 22 h.
Purification by flash chromatography (9:1 hexanes/EtOAc)
gave 77 mg (72%) of alcohol 14 as a clear oil: [R]20D 3.0 (c 0.64,
CHCl3); IR (film) ν 3473, 1748 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.30-7.15 (m, 5H), 4.68 (d, J ) 2.1 Hz, 2H), 4.37
(apparent s, 1H), 3.89 (dt, J ) 9.0, 3.0 Hz, 1H), 3.48 (m, 1H),
2.87 (ddd, J ) 13.2, 5.4, 1.8 Hz, 1H), 2.61 (m, 1H), 2.49 (m,
1H), 2.08 (m, 1H), 2.07 (s, 3H), 1.97-1.74 (m, 2H), 1.28 (d, J
) 7.2 Hz, 3H), 1.01 (t, J ) 7.5 Hz, 9H), 0.80 (d, J ) 6.9 Hz,
3H), 0.71 (q, J ) 7.5 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ
170.2, 142.0, 128.3, 128.2, 125.8, 87.8, 77.5, 75.9, 52.8, 41.5,
33.6, 33.2, 31.7, 30.5, 20.7, 17.4, 13.4, 6.8, 4.9. Anal. Calcd for
Exp er im en ta l Section
a n ti-5-Acetoxy-1-cycloh exyl-3-p en tyn -1-ol (3a ). To a
solution of Pd(OAc)2 (1.5 mg, 0.007 mmol) in THF (1.8 mL) at
-78 °C were added PPh3 (1.8 mg, 0.007 mmol), mesylate 1a
(88 mg, 0.40 mmol), and freshly distilled cyclohexanecarbox-
aldehyde (2a , 30 mg, 0.27 mmol) followed by dropwise addition
of diethylzinc (0.8 mL, 1 M in hexane, 0.8 mmol). The mixture
was immediately warmed to -20 °C. After 12 h, the reaction
mixture was quenched by dropwise addition of 10% HCl
(Ca u tion : evolu tion of ga seou s eth a n e) and diluted with
Et2O. After the mixture was warmed to room temperature,
the layers were separated and the ether layer was washed with
saturated brine. The aqueous layer was extracted with Et2O,
and the combined extracts were dried over MgSO4. The solvent
was removed under reduced pressure, and the residue was
chromatographed on silica gel (9:1 hexanes/EtOAc) to give 48
mg (75%) of alcohol 3a and its syn diastereomer as a 95:5
inseparable mixture.1
C
25H40O4Si: C, 69.40; H, 9.32. Found: C, 69.57; H, 9.35.
La cton e 17. To solution of alkyne 9 (290 mg, 0.76 mmol)
in THF (30 mL) at -78 °C was added dropwise n-BuLi (0.70
mL, 2.5 M in hexane, 1.75 mmol). The reaction mixture was
allowed to warm to -40 °C and stirred for 1 h. Carbon dioxide
was then bubbled through the solution for 15 min. The reaction
mixture was poured onto crushed dry ice, diluted with Et2O,
and acidified by dropwise addition of 10% HCl (Ca u tion :
evolu tion of ga seou s bu ta n e). The biphasic mixture was
allowed to warm to room temperature. The layers were
separated, and the aqueous layer was extracted twice with
Et2O. The combined Et2O layers were dried over MgSO4 and
concentrated under reduced pressure to give acid 15 (400 mg,
contaminated with pentanoic acid), which was used im-
mediately without purification.
To a solution of acid 15 (400 mg, contaminated with
pentanoic acid) in EtOH (15 mL) were added 5% Pd/BaSO4
(48 mg) and quinoline (24 mg, 0.19 mmol). The resultant
suspension was stirred vigorously for 1 h under a balloon
atmosphere of H2. After filtration through Celite with Et2O,
the solvents were removed under reduced pressure. The
residue was resubjected to the above conditions for 1 h to give
alkene 13 (400 mg, contaminated with pentanoic acid), which
was used immediately without purification.
(1R,2S)-(-)-5-Acetoxy-1-cycloh exyl-3-p en tyn -1-ol1 (3a ).
The standard procedure was employed with Pd(OAc)2 (4.0 mg,
0.018 mmol), PPh3 (4.7 mg, 0.018 mmol), mesylate (R)-1a (204
mg, 0.93 mmol), freshly distilled cyclohexanecarboxaldehyde
(2a , 80 mg, 0.71 mmol), and diethylzinc (2.1 mL, 1 M in
hexane, 2.1 mmol) in THF (7 mL) at -20 °C for 24 h to give
123 mg (72%) of alcohol 3a and its syn diastereomer as a 95:5
inseparable mixture: [R]20 -4.8 (c 0.65, CHCl3); IR (film) ν
D
1
3487, 2239, 1743 cm-1; H NMR (300 MHz, CDCl3) δ 4.66 (d,
J ) 1.9 Hz, 2H), 3.07 (m, 1H), 2.74 (m, 1H), 2.07 (s, 3H), 1.92
(d, J ) 12.3 Hz, 1H), 1.81-1.36 (m, 5H), 1.34-0.92 (m, 9H);
13C NMR (75 MHz, CDCl3) δ 170.3, 87.9, 78.6, 76.8, 52.7, 41.7,
30.0, 29.6, 28.1, 26.3, 26.2, 25.9, 20.7, 17.9.
A solution of alkene 16 (400 mg, contaminated with pen-
tanoic acid) in benzene (10 mL) was heated to reflux. After 4
h, the benzene was removed under reduced pressure, and the
residue was chromatographed on silica gel (9:1 hexanes/EtOAc)
(2S,3S,4S)-(+)-1-[(ter t-Bu t yld ip h en ylsilyl)oxy]-2,4-d i-
m eth yl-5-h exyn -3-ol (9). The standard procedure was em-
ployed with Pd(OAc)2 (2.7 mg, 0.012 mmol), PPh3 (3.1 mg,
0.012 mmol), mesylate (R)-1b (62 mg, 0.42 mmol), aldehyde
(S)-7 (80 mg, 0.24 mmol), and diethylzinc (0.74 mL, 1 M in
hexane, 0.74 mmol) in THF (1.7 mL) at -20 °C for 24 h.
Purification by flash chromatography (19:1 hexanes/EtOAc)
to give 203 mg (65%) of lactone 17 as a white powder: [R]20
D
-31.5 (c 1.63, CHCl3); mp 70-71 °C; IR (film) ν 1726 cm-1; 1H
NMR (300 MHz, CDCl3) δ 7.77-7.61 (m, 4H), 7.51-7.35 (m,
6H), 6.66 (d, J ) 10.0 Hz, 1H), 5.96 (d, J ) 10.0 Hz, 1H), 4.43
(d, J ) 10.8 Hz, 1H), 3.84 (apparent t, J ) 9.6 Hz, 1H), 3.62
(dd, J ) 10.0, 5.3 Hz, 1H), 2.65 (m, 1H), 2.03 (m, 1H), 1.10 (d,
J ≈ 7 Hz, 3H), 1.07 (s, 9H), 0.90 (d, J ) 6.9 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 164.2, 152.1, 135.4, 133.3, 129.6, 127.6,
120.0, 82.2, 64.9, 36.8, 30.4, 26.8, 19.1, 15.9, 9.7. Anal. Calcd
for C25H32O3Si: C, 73.49; H, 7.89. Found: C, 73.31; H, 7.99.
gave 65 mg (70%) of alcohol 9 as a clear oil: [R]20 +3.5 (c
D
1.01, CHCl3); IR (film) ν 3483, 3306 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.75-7.63 (m, 4H), 7.49-7.34 (m, 6H), 3.80-3.61 (m,
3H), 2.68 (m, 1H), 2.44 (bs, 1H), 2.00 (m, 1H), 1.87 (m, 1H),
1.21 (d, J ) 6.9 Hz, 3H), 1.09 (s, 9H), 0.99 (d, J ) 6.9 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 135.6, 133.4, 129.7, 127.7, 86.2,
75.6, 70.4, 67.4, 37.9, 30.5, 26.9, 19.2, 17.7, 10.6. Anal. Calcd
for C24H32O2Si: C, 75.74; H, 8.47. Found: C, 75.48; H, 8.41.
(2R,3S,4S)-(-)-1-[(ter t-Bu tyld ip h en ylsilyl)oxy]-2,4-d i-
m eth yl-7-a cetoxy-5-h ep tyn -3-ol9 (10). The standard proce-
dure was employed with Pd(OAc)2 (2.7 mg, 0.012 mmol), PPh3
(3.1 mg, 0.012 mmol), mesylate (R)-1a (193 mg, 0.42 mmol),
aldehyde (R)-7 (80 mg, 0.24 mmol), and diethylzinc (0.74 mL,
1 M in hexane, 0.74 mmol) in THF (1.7 mL) at -20 °C for 24
h. Purification by flash chromatography (9:1 hexanes/EtOAc)
Ack n ow led gm en t. This research was supported by
grant CHE 9220166 from the National Science Founda-
tion.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for 3a -d , 5, 6, 8, 11-13, and 20. This material is
available free of charge via the Internet at http://pubs.acs.org.
gave 90 mg (81%) of alcohol 10 as a clear oil: [R]20 -16.8 (c
J O9823083
D