3
812
J . Org. Chem. 1998, 63, 3812-3813
Syn th esis of Ch ir a l En a n tioen r ich ed
Hom op r op a r gylic Alcoh ols fr om P r op a r gylic
Mesyla tes via Ch ir a l Allen ylzin c
In ter m ed ia tes
Ta ble 1. Ad d ition s of a n Allen ylzin c Rea gen t,
Gen er a ted in Situ fr om P r op a r gylic Mesyla te 1, to
Ald eh yd es 2a -e
J ames A. Marshall* and Nicholas D. Adams
Department of Chemistry, University of Virginia,
Charlottesville, Virginia 22901
R
yield, %
anti:syna
ee,a-c
%
c-C6H11, a
85
70
56
71
60
95:5
95
90
86
88
90
Received April 8, 1998
C H13, b
88:12
86:14
77:23
68:32
6
d
TBSOCH2CH2, c
During the past several years, we have prepared chiral
allenyl tin and, more recently, indium reagents in connection
with the synthesis of stereotriad segments of polypropionate
(E)-BuCHdCH, d
1
-octynyl, e
a
Analysis by gas chromatography. b For the anti isomer. c
1
,2
natural products.
The approach entails the SN2′ displace-
Corrected for the ee of the starting material. d Analyzed as the
diol.
ment of propargylic mesylates I with a Bu3Sn cuprate
reagent to afford allenyl SnBu3 intermediates II of high ee.
These reagents undergo syn-selective SE2′ addition to alde-
hydes in the presence of BF3‚OEt2. Transmetalations with
InBr3 or SnCl4 (or BuSnCl3) afford transient InBr2 and SnCl3
(
or BuSnCl2) intermediates, which yield anti adducts IV or
1
ent-IV, respectively, upon addition to aldehydes (eq 1). The
alkynyl groups of these adducts can be utilized for introduc-
tion of additional Me- and OH-substituted stereocenters, as
required.
the (unknown) configurational stability of the transient
allenylzinc reagent.
To address these issues, we treated the (R)-mesylate 15
with 5 mol % of Pd(PPh3)4, 2.4 equiv of Et2Zn, and 1 equiv
of aldehydes 2a -e in THF at 0 °C to room temperature. This
combination led to propargylic adducts 3a -e as the sole
products (Table 1). These were analyzed by gas chroma-
6
tography and identified by comparison with known samples.
In all cases, the additions proceeded with good to excellent
anti selectivity and acceptable yield. Enantioselectivity was
uniformly high, but diastereoselectivity decreased according
to the steric requirements of the aldehyde.
A parallel series of additions was carried out starting from
the propargylic mesylate 4 (Table 2).1 The additions fol-
lowed a trend similar to those of mesylate 1 with regard to
diastereo- and enantioselectivity. The yields (unoptimized),
however, were somewhat lower in these preliminary experi-
ments.
Although the foregoing methodology has proven quite
useful for the construction of various subunits of polypro-
pionate natural products, the necessary involvement of
2
organotin compounds is viewed as a limitation with regard
to large-scale synthesis. Accordingly, we have been explor-
ing alternative allenylmetal reagents that might exhibit
similar high levels of enantio- and diastereoselectivity.
A recent report by Tamaru et al., describing the formation
of racemic or achiral allylic zinc species from allylic ben-
zoates or phenyl ethers and catalytic Pd(PPh3)4 in the
presence of excess Et2Zn, attracted our attention.3 We have
previously shown that propargylic mesylates undergo highly
stereoselective alkoxycarbonylation with catalytic Pd(PPh3)4,
CO, and alcohols affording allenic esters VI with net
inversion of stereochemistry (eq 2).4 If Zn metathesis of the
presumed allenylpalladium intermediate V could be effected
with comparable regio- and enantioselectivity, it may be
possible to produce a chiral allenylzinc reagent that would
afford enantioenriched homopropargylic alcohols upon ad-
dition to aldehydes. A successful outcome would depend on
To probe a potential application of this chemistry to the
2
synthesis of polypropionate subunits, we examined addi-
tions of the allenylzinc intermediate from mesylate 4 to the
1
R-methyl-â-benzyloxy aldehydes (S)- and (R)-6 (eq 3). In
1
the former case, the anti,syn product 7 was the sole adduct.
1
Addition to (R)-6 afforded the anti,anti adduct 8 in high
yield.
We also examined the propargylic acetate, trifluoroac-
etate, and methyl carbonate analogues of 1 as possible
precursors of the allenylzinc intermediate. No products were
obtained with the former two esters and cyclohexanecar-
boxaldehyde. The methyl carbonate derivative gave the
propargylic adduct 3a , but the yield (27%) and ee (29%) were
distinctly inferior to results obtained with the mesylate. The
mesylate reactions were carried out in several solvents
(
1) Marshall, J . A.; Perkins, J . F.; Wolf, M. A. J . Org. Chem. 1995, 60,
556.
2) Marshall, J . A.; Palovich, M. R. J . Org. Chem. 1997, 62, 6001.
Marshall, J . A.; Lu, Z.-H.; J ohns, B. J . Org. Chem. 1998, 63, 817.
3) Tamaru, Y.; Tanaka, A.; Yasui, K.; Goto, S.; Tanaka S. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 787.
4) Marshall, J . A.; Wolf, M. A.; Wallace, E. M. J . Org. Chem. 1997, 62,
67.
(C6H6, MeCN, CH2Cl2, and THF), but only MeCN and THF
5
gave homopropargylic alcohol adducts uncontaminated by
(
(
(5) The alcohol precursor is available from Aldrich Chemical Co.,
Milwaukee, WI.
(6) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1997, 62, 8976.
(
3
S0022-3263(98)00623-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/15/1998
Marshall, James A.
