Stereoselective radical carbon-carbon bond forming reactions of β-alkoxy esters: Atom and group transfer allylations under bidentate chelation controlled conditions

Article abstract of DOI:10.1021/ja9541241

The radical allylation of a series of β-alkoxy esters using allyltrimethylsilane in the presence of MgBr₂·OEt₂ is described. Under bidentate chelation-controlled conditions, allyltrimethylsilane rivals allyltributyltin in efficiency

Full text of DOI:10.1021/ja9541241

12528
J. Am. Chem. Soc. 1996, 118, 12528-12535
Stereoselective Radical Carbon-Carbon Bond Forming
Reactions of â-Alkoxy Esters: Atom and Group Transfer
Allylations under Bidentate Chelation Controlled Conditions
Y. Guindon,*,†,‡ B. Gue´rin,†,‡ C. Chabot,§ and W. Ogilvie§
Contribution from the Institut de recherches cliniques de Montre´al (IRCM), Bio-organic
Chemistry Laboratory, 110 aVenue des pins ouest, Montre´al, Que´bec, Canada H2W 1R7,
Department of Biochemistry and Chemistry, UniVersite´ de Montre´al,
Montre´al, Que´bec, Canada H3C 3J7, and Bio-Me´ga/Boehringer Ingelheim Research, Inc.,
2100 rue Cunard, LaVal, Que´bec, Canada H7S 2G5
ReceiVed December 7, 1995X
Abstract: The radical allylation of a series of â-alkoxy esters using allyltrimethylsilane in the presence of MgBr2‚
OEt2 is described. Under bidentate chelation-controlled conditions, allyltrimethylsilane rivals allyltributyltin in
efficiency and is a superior reagent from ecological and practical perspectives. The reactions work with iodides and
bromides as well as phenylselenides. The isolation of γ-phenylseleno intermediates indicates that the reaction proceeds
by an atom transfer process. These reactions require initiation with Et3B and can be inhibited by galvinoxyl, m- and
p-dinitrobenzene indicating that this atom transfer sequence involves the intermediacy of radicals.
Asymmetric induction in free radical reactions is a topic of
significant development in this field is the observation that
complexation with a Lewis acid can be used to enhance levels
of stereoselection or to reverse the facial bias of radical
reactions.6-9 Lewis acids have been shown to be compatible
with reduction, allylation, and â-addition processes. In this
current interest.1 Facial selectivity in radical reactions can be
influenced by a stereogenic center adjacent to a radical center
(1,2-induction)2-4 and by the use of chiral auxiliaries.5
A
* Author to whom correspondence should be addressed (IRCM).
† Institut de recherches cliniques de Montre´al.
‡ Universite´ de Montre´al.
§ Bio-Me´ga/Boehringer Ingelheim Research.
X Abstract published in AdVance ACS Abstracts, December 1, 1996.
(1) For reviews see: (a) Porter, N. A.; Giese, B.; Curran, D. P. Acc.
Chem. Res. 1991, 24, 296-304. (b) Smadja, W. Synlett 1994, 1-26. (c)
Miracle, G. S.; Cannizzaro, S. M.; Porter, N. A. Chemtracts 1993, 6, 147-
171(d) Giese, B.; Damm, W.; Batra, R. Chemtracts 1994, 7, 355-370. (e)
Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical Reactions
- Concepts, Guidelines and Synthetic Applications; VCH: New York, 1995.
(2) (a) Hart, D. J.; Huang, H.-C. Tetrahedron Lett. 1985, 26, 3749-
3752. (b) Hart, D. J.; Krishnamurthy, R. J. Org. Chem. 1992, 57, 4457-
4470 and refs cited therein. (c) Giese, B.; Damm, W.; Wetterich, F.; Zeitz,
H.-G. Tetrahedron Lett. 1992, 33, 1863-1866 and refs cited therein. (d)
Curran, D. P.; Ramamoorthy, P. S. Tetrahedron 1993, 49, 4841-4858 and
refs cited therein. See also ref 1.
paper we report results we have obtained in chelation-controlled
allylation reactions of R-halo-â-alkoxy esters using allyltri-
methylsilane and present evidence for a radical atom transfer
mechanism. To our knowledge, this represents the first example
of an atom transfer reaction in which facial selectivity is
controlled by Lewis acid complexation.10,11
(3) Bartlett, P. A.; Adams, J. L. J. Am. Chem. Soc. 1980, 102, 337-
342.
(4) (a) Guindon, Y.; Yoakim, C.; Lemieux, R.; Boisvert, L.; Delorme,
D.; Lavalle´e, J.-F. Tetrahedron Lett. 1990, 31, 2845-2848. (b) Guindon,
Y.; Lavalle´e, J.-F.; Boisvert, L.; Chabot, C.; Delorme, D.; Yoakim, C.; Hall,
D.; Lemieux, R.; Simoneau, B. Tetrahedron Lett. 1991, 32, 27-30. (c)
Durkin, K.; Liotta, D.; Rancourt, J.; Lavalle´e, J.-F.; Boisvert, L.; Guindon,
Y. J. Am. Chem. Soc. 1992, 114, 4912-4914. (d) Guindon, Y.; Yoakim,
C.; Gorys, V.; Ogilvie, W. W.; Delorme, D.; Renaud, J.; Robinson, G.;
Lavalle´e, J.-F.; Slassi, A.; Jung, G.; Rancourt, J.; Durkin, K.; Liotta, D. J.
Org. Chem. 1994, 59, 1166-1178. (e) Guindon, Y.; Slassi, A.; Rancourt,
J.; Bantle, G.; Bencheqroun, M.; Murtagh, L.; Ghiro, E.; Jung, G. J. Org.
Chem. 1995, 60, 288-289.
(5) Selected examples: (a) Crich, D.; Davies, J. W. Tetrahedron Lett.
1987, 28, 4205-4208. (b) Porter, N. A.; Scott, D. M.; Lacher, B.; Giese,
B.; Zeitz, H. G.; Lindner, H. J. J. Am. Chem. Soc. 1989, 111, 8311-8312.
(c) Curran, D. P.; Qi, H.; Geib, S. J.; DeMello, N. C. J. Am. Chem. Soc.
1994, 116, 3131-3132.
(6) Monodentate: (a) Renaud, P.; Moufid, N.; Kuo, L. H.; Curran, D.
P. J. Org. Chem. 1994, 59, 3547-3552. (b) Renaud, P.; Ribezzo, M. J.
Am. Chem. Soc. 1991, 113, 7803-7805. (c) Curran, D. P.; Kuo, L. H. J.
Org. Chem. 1994, 59, 3259-3261. (d) Nishida, M.; Ueyama, E.; Hayashi,
H.; Ohtake, Y.; Yamaura, Y.; Yanaginuma, E.; Yonemitsu, O.; Nishida,
A.; Kawahara, N. J. Am. Chem. Soc. 1994, 116, 6455-6456. (e) Renaud,
P.; Bourquard, T.; Gerster, M.; Moufid, N. Angew. Chem., Int. Ed. Engl.
1994, 33, 1601-1603. (f) Nishida, M.; Hayashi, H.; Yamaura, Y.;
Yanaginuma, E.; Yonemitsu, O. Tetrahedron Lett. 1995, 36, 269-272. (g)
Murakata, M.; Tsutsui, H.; Hoshino, O. J. Chem. Soc., Chem. Commun.
1995, 481-482. (h) Urabe, H.; Kobayashi, K.; Sato, F. J. Chem. Soc., Chem.
Commun. 1995, 1043-1044. (i) Moufid, N.; Renaud, P.; Hassler, C.; Giese,
B.; HelV. Chim. Acta 1995, 78, 1006-1012.
Results
A general mechanism for a typical atom transfer reaction is
shown in Scheme 1. In order to be successful, the reactivity of
(7) Bidendate: (a) Guindon, Y.; Lavalle´e, J. -F.; Llinas-Brunet, M.;
Horner, G.; Rancourt, J. J. Am. Chem. Soc. 1991, 113, 9701-9702. (b)
Guindon, Y.; Gue´rin, B.; Chabot, C.; Mackintosh, N.; Ogilvie, W. W.
Synlett. 1995, 449-451. (c) Guindon, Y.; Gue´rin, B.; Rancourt, J.; Chabot,
C.; Mackintosh, N.; Ogilvie, W. W. Pure Appl. Chem. 1996, 68, 89-96.
(d) Toru, T.; Watanabe, Y.; Tsusaka, M.; Ueno, Y. J. Am. Chem. Soc. 1993,
115, 10464-10465. (e) Ru¨ck, K.; Kunz, H. Synthesis, 1993, 1018. (f)
Nagano, H.; Kuno, Y. J. Chem. Soc., Chem. Commun. 1994, 987-988. (g)
Yamamoto, Y.; Onuki, S; Yumoto, M.; Asao, N. J. Am. Chem. Soc. 1994,
116, 421-422. (h) Wu, J. H.; Radinov, R.; Porter, N. A.; J. Am. Chem.
Soc. 1995, 117, 11029-11030. (i) Sibi, M. P.; Jasperse, C. P.; Ji, J. J. Am.
Chem. Soc. 1995, 117, 10779-10780. (j) Sibi, M. P.; Ji, J. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 190-192. (k) Sibi, M. P.; Ji, J. J. Am. Chem. Soc.
1996, 118, 3063-3064.
(8) Solvent complexation: (a) Waldner, A.; De Mesmaeker, A.; Hoff-
mann, P.; Mindt, T.; Winkler, T. Synlett 1991, 101-104. (b) De Mesmaeker,
A.; Waldner, A.; Hoffmann, P.; Mindt, T. Synlett 1993, 871-874
(9) Intramolecular hydrogen bonding: (a) Ku¨ndig, E. P.; Xu, L.-H.;
Romanens, P. Tetrahedron Lett. 1995, 36, 4047-4050. (b) Curran, D. P.;
Abraham, A. C.; Liu, H. J. Org. Chem. 1991, 56, 4335-4337. See also ref
2b.
S0002-7863(95)04124-2 CCC: $12.00 © 1996 American Chemical Society

C-C Bond Forming Reactions of â-Alkoxy Esters
J. Am. Chem. Soc., Vol. 118, No. 50, 1996 12529
Table 1. Radical Allylation Reactions of Iodoesters with
Allyltrimethylsilane under Chelation and Nonchelation Controlled
Conditions
Scheme 1
the participating species must be carefully modulated so that
chain propagation steps will dominate over standard chain
terminations. Conditions are especially favorable when the
initial radicals (1) have long enough lifetimes to allow radical
addition to occur (Step 1) and when the subsequent radicals
undergo rapid atom transfer with the donor species 4 (Step 2)
resulting in a viable chain reaction.11 A convenient way of
doing this is to use R-iodo esters as the atom donating
component. These types of substrates are well suited to atom
transfer reactions due to the presence of the ester adjacent to
the carbon bearing the radical. This functionality facilitates the
chain propagation steps by lowering the SOMO energy of radical
1 thus improving the overlap between the SOMO of the radical
and the HOMO of the olefin component. Lowering the SOMO
of this radical also encourages atom transfer.11 Malonate12 and
malononitrile13 benefit from an additional electron withdrawing
group and are especially useful if one wants to promote this
type of reaction.
ratiob
anti:syn
entry
substrate
conditionsa
yieldc
1
2
3
4
6:X ) OTBS
6:X ) OTBS
9:X ) OMe
9:X ) OMe
A
B
A
B
1:9.5
1:13
42:1
1:5
82
39
87
39
a A: 2.0 equiv of CH2CHCH2SiMe3, 1.0 equiv of MgBr2‚OEt2, 0.2
equiv of Et3B, CH2Cl2, -78 °C. B: 2.0 equiv of CH2CHCH2SiMe3,
0.2 equiv of Et3B, CH2Cl2, -78 °C. b Determined by NMR using crude
reaction mixtures. c Isolated combined yield.
Table 2. Radical Allylation of Various Substrates under Chelation
Control
In our earlier studies of chelation controlled radical
processes7a-c we noticed that hydrogen transfer and allylation
reactions involving R-halo esters proceeded more readily than
those done in absence of Lewis acid.14 Presumably complex-
ation between the carbonyl of the ester and the Lewis acid
increased the efficiency of these processes by rendering the ester
even more electronegative, thus lowering the SOMO energy of
these radicals. This hypothesis suggested to us that complex-
ation with a Lewis acid could perhaps be beneficial to the atom
transfer reaction. Control of diastereoselectivity through bi-
dentate chelation with Lewis acids in such reactions was as well
sought.
Preparation of Materials and Standards. The â-alkoxy
esters needed for this study were prepared by a variety of routes.
Secondary and tertiary anti iodides 9, 12, 15, 18, 21, 24, and
27 (Table 2) and secondary bromide 36 (Table 3) were prepared
by a halo etherification reaction as described by Vishwakarma
and Walia.15 Phenylselenide 37 was synthesized by using a
modification of this method in which silver triflate, a soluble
silver salt, was used in place of silver nitrate. Syn substrates
38, 39, and 40 (Table 3) were prepared from the appropriate Z
olefin using procedures analogous to those of the corresponding
anti substrates.15 Tetrahydropyran 30 and tetrahydrofuran 33
(Table 2) were obtained by an iodocyclization reaction involving
the appropriate R, â-unsaturated ester.4d Silyl ether 6 (Table
1) was readily derived from the previously described secondary
alcohol.16
a Conditions: 2.0 equiv of CH2CHCH2SiMe3, 1.0 equiv of MgBr2‚
OEt2, 0.2 equiv of Et3B, CH2Cl2, -78 °C. b Determined by GC using
crude reaction mixtures. c Isolated yield of major product. d Ethyl ester
was used. e R-Hydroxy-â-alkoxy esters were obtained in ca. 40% yield.
Table 3. Effect of the Relative Configuration and R-Substituent of
Substrates on Chelation Controlled Radical Allylations
ratioa,b
10:11
entry
substrate
yieldc
1
2
3
4
5
6
7
9:Y ) H, Z ) I
42:1
>100:1
>100:1d
87
67
75
0e
72
48
0e
36:Y ) H, Z ) Br
37:Y ) H, Z ) SePh
38:Y ) I, Z ) H
39:Y ) Br, Z ) H
40:Y ) SePh, Z ) H
38:Y ) I, Z ) Hf
10:1
(10) For other examples of stereoselective atom transfer reactions see:
(a) Curran, D. P.; Geib, S. J.; Kuo, L. H. Tetrahedron Lett. 1994, 35, 6235-
6238. (b) Thoma, G.; Curran, D. P.; Geib, S. V.; Giese, B.; Damm, W.;
Wetterich, F. J. Am. Chem. Soc. 1993, 115, 8585-8591. (c) Curran, D. P.;
Thoma, G. Tetrahedron Lett. 1991, 32, 6307-6310.
(11) For reviews see: (a) Curran, D. P. Synthesis 1988, 489-513. (b)
Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. ReV. 1991, 91, 1237-
1286. See also ref 10.
100:1d
a Conditions: 2.0 equiv of CH2CHCH2SiMe3, 1.0 equiv of MgBr2‚
OEt2, 0.2 equiv of Et3B, CH2Cl2, -78 °C. b Determined by GC using
crude reaction mixtures. c Isolated yield of major product. d Ratio
determined after chromatography (see text). e Starting material is
consumed, ca. 40% R-hydroxy ester obtained. f Conditions: 2.0 equiv
of CH2CHCH2SiMe3, 0.2 equiv of Et3B, CH2Cl2, -78 °C.
(12) Curran, D. P.; Chang, C.-T. J. Org. Chem. 1989, 54, 3140-3157.
(13) Curran, D. P.; Seong, C.-M. J. Am. Chem. Soc. 1990, 112, 9401.
(14) Lewis acid accelerations have been noted in other radical process:
(a) Newcomb, M.; Ha, C. Tetrahedron Lett. 1991, 32, 6493-6496. (b)
Urabe, H.; Yamashita, K.; Suzuki, K.; Kobayashi, K.; Sato, F. J. Org. Chem.
1995, 60, 3576-3577. See also ref 7d.
The relative configurations of the acyclic allylated products
were established by independent synthesis and correlation of
NMR spectra. The propensity of the aldol reaction to give syn
adducts was capitalized upon to obtain adduct 4317 which was
methylated using MeOTf and Proton-sponge to give syn adduct
14 (Scheme 2). This compound, along with the known adducts
(15) Vishwakarma, L. C.; Walia, J. S. J. Indian Chem. Soc. 1976, 53,
156-162
(16) Cambie, R. C.; Chambers, D.; Rutledge, P. S.; Woodgate, P. D. J.
Chem. Soc., Perkin Trans. 1 1977, 20, 2231-2235.
(17) Fra´ter, G.; Mu¨ller, U.; Gu¨nther, W. Tetrahedron 1984, 40, 1269-
1277. See also Reference 2b.

12530 J. Am. Chem. Soc., Vol. 118, No. 50, 1996
Guindon et al.
Scheme 2
Scheme 4
Scheme 3
Table 4. Effect of Radical Inhibitors on Chelation Controlled
Allylations using Allyltrimethylsilane
102b and 11,2b was used as a standard to characterize the
allylation products of the corresponding secondary iodides
(Table 2). The relative configuration of the quaternary allylated
products was determined by treating anti adduct 25 (Table 2,
entry 6), with Me2BBr18 at 0 °C to give â-hydroxy ester 44
whose NMR spectrum was identical to that previously reported17
(Scheme 3). In a similar manner, syn adduct 26 was cleaved
to give the known product 45.17 The relative configurations of
the remaining tertiary and quaternary acyclic products were
deduced by correlation of NMR spectra19 with products 10,2b
11,2b 14, 22,2b 23,2b 25, and 26. In all cases, the difference in
chemical shift between the NMR resonances of the methylene
protons of the allyl side chain (∆υ) of the anti diastereomers
were greater than the values of ∆υ for the syn diastereomers.
The chemical shifts of the resonances of these same hydrogens
in the anti series were also consistently upfield to those
resonances of the corresponding syn diastereomers.20
The relative configurations of cyclic products 31, 32, 34, and
35 (Table 2, entries 8 and 9) were determined by correlation of
their NMR spectra with those of silyl ethers 46 and 48.7b These
compounds were chosen as references since the relative
configurations of the asymmetric centers could be determined
easily. As shown in Scheme 4, exposure of anti adduct 46 to
5% HF in CH3CN resulted in the formation of lactone 47. NOE
analysis of this material showed strong interactions between Ha
and Hb and between Ha and Hc indicating that these three
hydrogens are located on the same face of the bicyclic lactone
and hence that the configuration of 46 is anti. Hydrolysis of
silyl ether 48 gave lactone 49, in which there is a weak NOE
interaction between Ha and Hc. In addition, there was no
coupling observed between Ha and Hc in this adduct suggesting
a 90° dihedral angle between these two hydrogens. This is only
possible if Ha and Hc are trans to one another, and hence
compound 48 must have a syn configuration. The configurations
of exocyclic substrates 31, 32, 34, and 35 were deduced by
correlation of NMR spectra with those of anti and syn
compounds 46 and 48 (see above).19
entry
substrate
inhibitor
yielda
1
2
3
4
5
6
7
8
9:X ) I
none
87
7
4
9:X ) I
1,3-DNB
1,4-DNB
galvinoxyl
none
1,4-DNB
none
9:X ) I
9:X ) I
3
36:X ) Br
36:X ) Br
37:X ) SePh
37:X ) SePh
67
trace
75
trace
1,4-DNB
a Determined by H NMR integration of crude reaction isolates.
1
transfer reactions. Thus silyl derivative 6 was allowed to react
with allyltrimethylsilane21 in the presence of MgBr2‚OEt2. This
reaction proceeded readily and in good yield (Table 1, entry 1)
providing the syn product 8 in a 9.5:1 ratio. In the absence of
MgBr2‚OEt2 however, this same transformation resulted in a
poor yield of allyl transfer product (entry 2) in a 13:1 ratio in
favor of the syn isomer. The next obvious step was to replace
the silyl ether by another protecting group (e.g., OMe) that
would permit the formation of a bidentate intermediate and to
evaluate its effect. As shown in entries 3 and 4, the yield was
once again improved by the addition of MgBr2‚OEt2; more
importantly a reversal in the facial selectivity of the reaction
was also observed consistent with bidentate chelation.
Other secondary acyclic iodides underwent allylation with
excellent selectivity when treated with allyltrimethylsilane and
MgBr2‚OEt2, furnishing ratios higher than 100:1 (Table 4, entries
2, 3, and 4).22 Tertiary acyclic iodides all displayed excellent
diastereoselectivities in the present chelation controlled reaction;
unfortunately poor yields were observed (entries 5, 6, and 7).23
In these cases, lower substrate reactivity (reflected by longer
reaction times) results in competitive formation of the corre-
sponding R-hydroxy esters. The formation of these types of
products is presumably a result of chain termination by
(21) This reagent is reported to give allyl adducts through an atom
transfer/elimination sequence. (a) Curran, D. P.; Chen, M.-H.; Spletzer, E.;
Seong, C. M.; Chang, C.-T. J. Am. Chem. Soc. 1989, 111, 8872-8878. (b)
Hwu, J. R.; Chen, C. N.; Shiao, S.-S. J. Org. Chem. 1995, 60, 856-862.
(c) Hirao, T.; Fujii, T.; Ohshiro, Y. Tetrahedron Lett. 1994, 35, 8005-
8008 and refs cited therein.
(22) Ratios were determined by GC using crude reaction mixtures. These
ratios were comparable to those obtained by NMR spectroscopy. In the
case of the phenyl and cyclohexyl substituted secondary substrates (9 and
15, Table 2, entries 1 and 3), the GC and NMR results were calibrated
using product mixtures of varying composition.
Allylation Reactions. With the required substrates and
stereochemical tools in hand we proceeded to try the atom
(18) (a) Guindon, Y.; Yoakim, C.; Morton, H. E. Tetrahedron Lett. 1983,
24, 2969. (b) Guindon, Y.; Therien, M.; Girard, Y.; Yoakim, C. J. Org.
Chem. 1987, 52, 1680. (c) Guindon, Y.; Anderson, P. C. Encyclopedia of
Reagents for Organic Synthesis; Paquette, L. A. Ed.; Wiley & Sons: New
York, 1995; pp 715-718.
(19) Tables of the chemical shift data used to make these correlations
can be found in the supplementary material.
(20) A similar trend has been observed in the case of reduction. See ref
4 and: Gouzoules, F. H.; Whitney, R. A. J. Org. Chem. 1986, 51, 2024-
2030.
(23) A similar drop in reactivity has been previously observed for other
tertiary iodides. Curran, D. P.; Kim, D.; Ziegler, C. Tetrahedron 1991, 47,
6189-6196.

C-C Bond Forming Reactions of â-Alkoxy Esters
J. Am. Chem. Soc., Vol. 118, No. 50, 1996 12531
Scheme 5
Scheme 6
combination with peroxyborate radicals.24 We have noted that
R-iodo-â-alkoxy esters react slowly with Et3B and oxygen to
give the corresponding R-hydroxy esters with relatively low
diastereoselectivity as illustrated in Scheme 5.25,26
Scheme 7
We were interested in probing the effect of bicyclic bidentate
complex formation in the present reaction. In the presence of
MgBr2‚OEt2, the allylation of tetrahydropyranyl substituted iodo
ester 30 gave a ratio of 27:1 in favor of the anti product (entry
8). In contrast, almost no selectivity was observed when the
corresponding tetrahydrofuranyl derivative 33 was subjected to
the same reaction conditions (entry 9). This reactivity pattern
was previously observed in the case of the analogous reaction
using allyltributyltin.7b It is possible that the formation of a
bicyclic [3.3.0] intermediate in the reaction of tetrahydrofuranyl
derivative 33 is disfavored sterically (see below).
In addition to iodides, bromides and phenylselenides27 were
able to function as substrates in the reaction (Table 3, entries
1-3). As anticipated from previous observations using Bu3-
SnH or allyltributyltin,7a,b we were expecting a decrease in
diastereoselectivity for the syn iodo isomer. We were somewhat
surprised to note that while anti iodide 9 underwent a facile
allylation reaction with allyltrimethylsilane, the corresponding
syn iodide 38 did not (entries 1 and 4). When syn iodide 38
was treated with allyltrimethylsilane in the presence of MgBr2‚
OEt2 the starting material was consumed but almost no allylated
product was found.28 A similar unexplained result was also
observed in the absence of Lewis acid (entry 7).29 This effect
was only minor in the case of bromides (entries 2 and 5) and
absent in the case of phenylselenides (entries 3 and 6).
To prove that an atom transfer mechanism was operative,
we examined the reaction of phenylselenide substrate 37 since
the initially formed adduct (57) should be relatively stable
(Scheme 6). This was in fact the case; we noticed the presence
of a new product in the NMR spectrum of the crude reaction
mixture. Careful chromatography using silica neutralized with
Et3N afforded the intermediate phenylselenide 57 as a 4:1
mixture of isomers, epimeric at the carbon â to silicon.30
Subjecting this material to flash chromatography affords com-
pound 11 (>100:1 anti:syn). A similar intermediate (56) was
detected in the crude reaction mixtures when the corresponding
bromide 36 was treated with allyltrimethylsilane and MgBr2‚
OEt2 under the same conditions. This compound proved to be
too labile to be isolated but could be converted to alkylsilane
58 by reduction with Bu3SnH. Unfortunately the same experi-
ment could not be done with iodide 9 as the subsequent
elimination was extremely rapid.
We have performed several experiments to prove whether
the initial atom transfer reaction is radical based. Triethyl-
borane24,31 was required to initiate the reaction with all of the
substrates studied, implying that this process involves a radical
chain. The reaction could also be terminated by the presence
of inhibitors (Table 4). In all cases when inhibitors were used
(entries 2, 3, 4, 6, and 8), the intermediate adducts (55, 56, and
57) were not observed and virtually all of the starting material
was recovered. This was true of iodides, bromides, and
phenylselenides. Taken together these are good indications that
the stereofacial-determining, carbon-carbon bond forming step
of the process is indeed a radical reaction.
Discussion
This work illustrates the first use of bidentate chelation to
control facial selectivity in atom and group transfer reactions.
This complements the use of Lewis acids in reduction, allylation
and â-addition. As illustrated in Table 2 the use of allyltri-
methylsilane leads to the overall addition of an allyl group with
very high selectivity. One substrate class which does not give
high selectivity however are those iodides exocyclic to a
tetrahydrofuran ring (Entry 9). As shown in Scheme 7, the
formation of a chelate in the tetrahydrofuran system may be
impaired by eclipsing interactions between the C-O bond and
an Mg-Br bond in the bicyclo [3.3.0] complex. For this reason
the acyclic (monodentate or uncomplexed) pathway becomes
competitive in the tetrahydrofuran series resulting in low
selectivity. In the tetrahydropyran case the bicyclic complex
does not suffer the same type of interactions and therefore the
equilibrium favors the bidentate chelated complex.
(24) Brown, H. C.; Midland, M. M.; Kabalka, G. W. J. Am. Chem. Soc.
1971, 93, 1024-1025.
(25) We are on one hand trying to avoid this reaction pathway and on
the other hand trying to optimize it for a different application. Guindon,
Y.; Yoakim, C.; Soucy, F. unpublished results.
(26) Details of this reaction including proof of configuration will be
published elsewhere.
(27) For examples of group transfer reactions involving selenium see:
(a) Beyers, J. H.; Harper, B. C. Tetrahedron Lett. 1992, 23, 6953-6954.
(b) Curran, D. P.; Martin-Esker, A. A.; Ko, S.-B.; Newcomb, M. J. Org.
Chem. 1993, 58, 4691-4695 and refs cited therein. See also ref 10a.
(28) The reaction mixture contained ca. 40% of the R-hydroxy-â-alkoxy
ester.
(29) We have found in several radical processes that there is often a
large difference in reactivity between syn and anti iodide diastereomers.
The fact that two such diastereomers can have such dissimilar behaviors is
very intriguing, and we are currently investigating this phenomenon.
(30) The same intermediate was observed when syn phenylselenide 40
was used.
That this process involves a radical based process is indicated
by the requirement of initiation and by the observation that
radical inhibitors are able to prevent the reaction from occurring.
(31) Nozaki, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991,
64, 403-409.

12532 J. Am. Chem. Soc., Vol. 118, No. 50, 1996
Guindon et al.
combined ether extracts were washed with 10% Na2S2O3, water, and
brine and dried over MgSO4. Flash chromatography (25% EtOAc in
hexanes) afforded the iodohydrin as a white solid (3.02 g). Mp 98-
99 °C; 1H NMR (400 MHz, CDCl3) δ 3.36 (s, 1H), 3.78 (s, 3H), 4.59
(d, J ) 8 Hz, 1H), 5.09 (d, J ) 6 Hz, 1H), 7.32-7.39 (m, 5H); 13C
NMR (50.3 MHz, CDCl3) δ 24.37, 53.01, 76.17, 126.88, 128.48,
128.66, 139.31, 171.60; IR (CHCl3) 3672, 3090, 1726, 1350, 1300,
1230, 1004 cm-1; MS (FAB) 307 (MH+); HRMS calcd for C10H12IO3
(M+) 306.9831, found 306.9844. To a solution of this alcohol (500
mg, 1.634 mmol) and 2,6-lutidine (380 µL, 3.268 mmol) in CH2Cl2
(15 mL) at -78 °C was added slowly tert-butyldimethylsilyl trifluo-
romethanesulfonate (560 µL, 2.451 mmol). After the reaction was
judged to be complete by TLC, the mixture was diluted with ether and
washed with water, saturated NH4Cl, and brine. Drying over MgSO4
followed by flash chromatography (5% EtOAc in hexanes) afforded
silyl ether 6 as a white solid (690 mg, 98%). Mp 95-97 °C; 1H NMR
(400 MHz, CDCl3) δ -0.31 (s, 3H), 0.01 (s, 3H), 0.78 (s, 9H), 3.79
(s, 3H), 4.38 (d, J ) 10.0 Hz, 1H), 5.05 (d, J ) 10 Hz, 1H) 7.34-7.36
(m, 5H); 13C NMR (50.3 MHz, CDCl3) δ -4.61, -4.82, 17.83, 25.37,
27.60, 52.66, 77.42, 127.59, 128.03, 128.49, 140.45, 170.73; IR (neat)
2955, 1737, 1436, 1270, 1202, 1170 cm-1; MS (FAB) 421 (MH), 363;
HRMS calcd for C16H26IO3Si (MH+) 421.0696, found 421.0669; Anal.
Calcd for C16H25IO3Si: C, 45.71; H, 6.00. Found: C, 45.30; H, 5.93.
General Procedure for the Preparation of Iodides 9, 12, 15, 18,
21, 24, and 27.15 To a solution of methyl cinnamate (5.05 g, 31.1
mmol) in methanol (70 mL) was successively added AgNO3 (15.81 g,
62.2 mmol) and iodine (10.6 g, 62.2 mmol). The reaction mixture
was stirred at room temperature in the dark for 6 h, then filtered through
Celite, and concentrated. The residue was taken up in ether and washed
with 10% Na2S2O3, water, and brine. The organic layer was dried
(MgSO4), filtered, and concentrated to afford a residue which was
purified by flash chromatography to afford pure iodide 915 as a white
solid (10 g, 78%). Iodides prepared in this manner were stable for
several months if kept in a freezer.
The fact that the ratios of products obtained using allyltri-
methylsilane with and without Lewis acid are the same as those
of the corresponding reactions performed using allyltributyltin7b
suggests that the stereofacial-determining step (radical addition)
is the same for both processes.
The inclusion of MgBr2‚OEt2 also appears to improve the
efficiency of the overall atom transfer process for the present
series of substrates. In the absence of Lewis acid, allylation
does occur in most cases; however, the reaction suffers from
competitive chain terminating processes, particularly hydroxy-
lation.32 This is reflected in the low yields obtained when
allyltrimethylsilane was used in the absence of Lewis acid and
in the contrast in overall quality between reactions performed
with and without Lewis acid. One notable exception to this is
the case of syn iodide 38, whereas the addition of MgBr2‚OEt2
was not sufficient to avoid this reaction pathway.
The overall results of this study suggests that a Lewis acid
may be used to improve the reactivity of substrates that do not
give facile atom transfer. We are now pursuing this possibility
in order to better define the scope and limitations of this reaction.
Is this improvement in reaction efficiency attributable to a
more rapid atom transfer (Step 2, Scheme 1) or to an accelerated
addition step (Step 1)? In principle both steps could be
implicated. Coordination of the Lewis acid to the ester would
make this group more electronegative potentially improving the
atom donating ability of these complexes (50, 51, and 52
Scheme 6). The addition step may as well be influenced by
rendering the ester group more electronegative. This may
decrease the SOMO energy of the intermediate radical (53) thus
permitting a better overlap with the HOMO of the allylsilane
olefin. The fact that tertiary substrates give poor results relative
to the secondary series (Table 2) may suggest that it is the
addition step which is affected since tertiary iodides should be
better atom donors than secondary ones.11,23 Firm conclusions
will have to wait for a better understanding of the hydroxylation
reactions and of the influence of Lewis acid on the kinetic
characteristics of these processes.
Dissecting these reactions is not a trivial exercise. In principle
there could be at least three distinct competing reaction pathways
(not considering the hydroxylation pathways): the uncomplexed
pathway giving a preference for the syn product; the monoden-
tate intermediate which also leads to the syn product; and the
bidentate pathway leading to the anti product. The overall
kinetic preference of one pathway with respect to the others
will affect the outcome of the reaction. The need for equimolar
amounts of MgBr2‚OEt2 in the reaction mixture suggests that
the bidentate pathway may not benefit from a strong kinetic
bias. The implications of the nature of the Lewis acid,33 its
solubility and the stability of the complex generated are aspects
we are presently considering. In conclusion, we have described
herein studies that support the use of Lewis acids in atom
transfer processes both for the improvement of the efficiency
of this reaction when needed, as well as to control the
diastereoselectivity of the reaction when bidentate Lewis acids
are used.
Methyl (2R*,3R*)-2-Iodo-3-methoxy-butanoate (12). Colorless
1
oil, H NMR (200 MHz, CDCl3) δ 1.39 (d, J ) 6.1 Hz, 3H), 3.35 (s,
3H), 3.61 (dd, J ) 6.1, 8.8 Hz, 1H), 3.75 (s, 3H), 4.23 (d, J ) 8.8 Hz,
1H); 13C NMR (50.3 MHz, CDCl3) δ 17.52, 24.99, 52.55, 57.25, 77.64,
170.35; IR (neat) 2980, 2830, 1740, 1440, 1305, 1220, 1150, 1100
cm-1; MS (CI, CH4) 259 (MH+, 100), 244 (15), 227 (79), 199 (18),
175 (19), 131 (48), 101 (48); HRMS calcd for C6H11IO3 (MH) 257.9753,
found 257.9746.
Methyl (2R*,3R*)-2-Iodo-3-methoxy-3-cyclohexylpropanoate (15).
1
Colorless oil, H NMR (200 MHz, CDCl3) δ 1.09-1.74 (m, 10H),
2.03-2.07 (m, 1H), 3.44 (s, 3H), 3.55 (dd, J ) 2.3, 10.2 Hz, 1H),
3.76 (s, 3H), 4.26 (d, J ) 10.2 Hz, 1H); 13C NMR (50.3 MHz, CDCl3)
δ 20.94, 24.32, 25.82, 26.09, 26.28, 30.57, 39.82, 52.56, 61.58, 85.49,
171.15; IR (neat) 2940, 2860, 1740, 1440, 1280, 1220, 1170, 1110
cm-1; MS (CI,CH4) 327 (MH+,33), 295 (100), 263 (18), 168 (32), 127
(17); HRMS calcd for C11H19O3I (M+) 326.0381, found 326.0398; Anal.
Calcd for C11H19IO3: C, 40.51; H, 5.87. Found: C, 40.85; H, 6.00.
Methyl (2R*,3R*)-2-Iodo-3-methoxy-4-methylpentanoate (18).
Colorless oil, 1H NMR (400 MHz, CDCl3) δ 0.84 (d, J ) 6.8 Hz,3H),
1.05 (d, J ) 7 Hz, 3H), 2.40 (m, 1H), 3.48 (s, 3H), 3.61 (dd, J ) 2.4,
10.2 Hz, 1H), 3.78 (s, 3H), 4.22 (d, J ) 10.3 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 13.96, 20.37, 21.61, 29.88, 52.68, 61.84, 85.78, 171.32;
IR (neat) 2960, 1740, 1435, 1367, 1200, 995 cm-1; MS (FAB) 287
(MH, 26), 128 (16), 87 (100); HRMS calcd for C8H15IO3 (MH)
287.0144, found 287.0120.
(34) General Methods: Melting points were determined on an elec-
trothermal melting point apparatus and are uncorrected. NMR spectra were
recorded on a Bruker AC200 or Bruker AMX400 spectrometer and are
referenced to TMS as internal standard. IR spectra were recorded on a
Perkin-Elmer 781 spectrophotometer. CI and EI mass spectra were recorded
on an MF 50 TATC instrument operating at 70 eV. Capillary GC analyses
were performed on a Shimadzu GC-9AM instrument using a 0.25 mm ×
25 m Chromatopac C-R3A column. Flash chromatography was performed
on Merck silica gel 60 (0.040-0.063 mm) using nitrogen pressure.
Analytical thin-layer chromatography (TLC) was carried out on precoated
(0.25 mm) Merck silica gel F-254 plates. All reactions were conducted under
a positive nitrogen atmosphere in oven-dried glassware using standard
syringe techniques. Tetrahydrofuran (THF) and ether were distilled from
sodium/benzophenone immediately prior to use. Dichloromethane (CH2-
Cl2), (iPr)2EtN and diisopropylamine were distilled from calcium hydride.
Methanol was distilled from magnesium.
Experimental Section34
Methyl (2R*,3R*)-2-Iodo-3-[((1, 1-dimethylethyl)dimethylsilyl)-
oxy]-3-phenylpropanoate (6). To a solution of methyl cinnamate (1.70
g, 10.52 mmol) in water (37 mL) and acetone (18 mL) was successively
added N-iodosuccinimide (4.73 g, 21.04 mmol) and H2SO4 (180 µL).
The reaction was stirred at 25 °C until judged to be no more than 50%
complete by TLC. The mixture was then extracted with ether, and the
(32) This hydroxylation pathway was not observed in the analogous
reaction performed using allyltributyltin. See ref 7b.
(33) For a recent example of the effect of the nature of Lewis acid on
reaction pathways see ref 7k.

C-C Bond Forming Reactions of â-Alkoxy Esters
J. Am. Chem. Soc., Vol. 118, No. 50, 1996 12533
Methyl (2R*,3R*)-2-Iodo-2-methyl-3-methoxy-3-phenylpropanoate
(21). White solid, mp 76-77 °C; 1H NMR (200 MHz, CDCl3) δ 1.97
(s, 3H), 3.21 (s, 3H), 3.85 (s, 3H), 5.00 (s, 1H), 7.31-7.53 (m, 5H);
13C NMR (50.3 MHz, CDCl3) δ 23.80, 42.37, 52.97, 57,75, 87.12,
127.45, 128.41, 129.91, 135.11, 172.67; IR (CHCl3) 3030, 2960, 2940,
1735, 1455, 1250, 1100 cm-1; MS (CI, CH4) 335 (MH+, 21), 303 (59),
207 (21), 175 (100), 121 (21); HRMS calcd for C12H15IO3 (M+)
334.0066, found 334.0082.
was diluted with ether and successively washed with 10% aqueous
Na2S2O3, water, and brine. The organic layer was dried (MgSO4),
filtered, and concentrated to afford a 1:1 mixture of iodides 9 and 38.
Iodide 38 can be obtained in pure form by flash chromatography using
1
CH2Cl2. White solid; mp 47-48 °C; H NMR (200 MHz, CDCl3) δ
7.30-7.40 (m, 5 H), 4.52 (d, J ) 9.9 Hz, 1H), 4.43 (d, J ) 9.9 Hz,
1H), 3.54 (s, 3H), 3.27 (s, 3H); 13C NMR (50.3 MHz, CDCl3) δ 26.42,
52.58, 57.06, 83.87, 127.43, 128.61, 128.81, 136.74, 164.60; IR (neat)
3060, 3025, 2985, 2940, 2815, 1735, 1490, 1455, 1435, 1350, 1295,
1265, 1165, 1005 cm-1; HRMS calcd for C11H13IO3, 319.9909, found
319.9885.
Methyl (2R*,3R*)-2-Iodo-2-methyl-3-methoxybutanoate (24). Col-
1
orless oil; H NMR (400 MHz, CDCl3) δ 1.31 (t, J ) 7.12 Hz, 3H),
1.46 (d, J ) 6.3 Hz, 3H), 1.98 (s, 3H), 3.33 (s, 3H), 4.06 (q, J )
6.3Hz, 1H), 4.25 (m, J ) 7.1 Hz, 2H); 13C NMR (100 MHz, CDCl3)
δ 13.98, 14.02, 23.67, 43.19, 57.86, 61.90, 81.58, 172.54; IR (neat)
2980, 2825, 1732, 1378, 1252, 1132, 990 cm-1; this compound would
not give a satisfactory mass spectrum.
Methyl (2S*, 3R*)-2-Bromo-3-methoxy-3-phenylpropanoate (39).
To a solution of Z-methyl cinnamate (0.63 g, 3.9 mmol) in methanol
(20 mL) was successively added AgNO3 (2.0 g, 11.7 mmol) and
bromine (0.6 mL, 11.7 mmol). The reaction mixture was stirred at
room temperature in the dark for 0.5 h, then filtered through Celite,
and concentrated. The residue was taken up in ether and washed with
10% Na2S2O3, water, and brine. The organic layer was dried (MgSO4),
filtered and concentrated to afford a residue which was purified by
flash chromatography to afford the bromide as a colorless oil (0.83 g,
78%). Bromides prepared in this manner were stable for several months
if kept in a freezer. Colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.30
(s, 3H), 3.56 (s, 3H), 4.39 (d, J ) 8.9 Hz, 1H), 4.55 (d, J ) 8.9 Hz,
1H), 7.33-7.36 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 49.75, 52.64,
57.14, 83.37, 127.54, 128.54, 128.93, 136.58, 167.96; IR (neat) 2950,
2826, 1744, 1494, 1454, 1300, 1100, 980 cm-1; MS (FAB) 273 (MH,
68), 243 (69), 217 (100), 163 (31), 121 (69); HRMS calcd for C11H14-
BrO3 (MH) 273.0126, found 273.0115; Anal. Calcd for C11H13BrO3:
C, 48.37; H, 4.80. Found: C, 48.43; H, 4.74.
Methyl (2R*,3R*)-2-Iodo-2, 4-dimethyl-3-methoxypentanoate
1
(27). Colorless oil; H NMR (200 MHz, CDCl3) δ 1.11 (t, J ) 7Hz,
3H), 1.33 (t, J ) 7 Hz, 3H), 1.49-1.74 (m, 1H), 1.97 (s, 3H), 2.15-
2.35 (m, 1H), 3.47 (s, 3H), 3.83 (dd, J ) 2, 10 Hz, 1H), 4.21-4.32
(m, 2H); 13C NMR (50.3 MHz, CDCl3) δ 12.0, 13.6, 23.9, 24.9, 43.8,
60.9, 61.6, 87.5, 172.2; IR (neat) 1735 cm-1; MS (CI, NH3) m/e (relative
intensity) 318 (M+ + NH4, 100), 301 (M+ + H, 6); HRMS calcd for
C9H17O3I (M+) 300.0256, found 300.0240; Anal. Calcd for C9H17IO3:
C, 36.01; H, 5.71. Found: C, 35.99; H, 5.77.
General Procedure for the Preparation of Iodides 30 and 33.
To a stirred solution of methyl 6-hydroxyhex-2-enoate (1.13 g, 7.87
mmol) in THF (30 mL) at room temperature was added NaHCO3 (3.30
g, 39.3 mmol) and then iodine (10.0 g, 39.3 mmol). After 24 h of
stirring the resultant mixture was diluted with ether, washed with 10%
Na2S2O3 and brine, and dried over MgSO4. Removal of solvent gave
an oil which was then purified by flash chromatography to give the
desired product 33 (1.10 g, 51%). Iodides 30 and 33 are stable for
several months if kept in a freezer.
Methyl (2R*,3R*)-3-[Tetrahydropyran-2-yl]-2-iodopropanoate
(30). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.06-1.20 (m, 1H),
1.31-1.56 (m, 3H), 1.80-1.87 (m, 1H), 2.14-2.20 (m, 1H), 3.37-
4.04 (m, 1H), 3.53-3.60 (m, 1H), 3.72 (s, 3H), 3.86-3.92 (m, 1H),
4.11 (d, J ) 9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 23.20, 24.06,
25.24, 30.05, 52.77, 68.94, 78.02, 171.20; IR (neat) 2960, 1730,
1430cm-1; MS (FAB) 285 (MH, 100), 253 (18), 154(92), 137(77);
HRMS calcd for C8H14IO3 (MH) 284.9988, found 284.9960.
Methyl (2R*,3R*)-3-[Tetrahydrofuran-2-yl]-2-iodopropanoate
(33). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.80-1.87 (m, 1H),
1.88-1.98 (m, 2H), 2.25-2.30 (m, 2H), 3.76 (s, 3H), 3.87-3.97 (m,
2H), 4.20 (d, J ) 9.5 Hz, 1H), 4.31-4.37 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 24.43, 25.92, 31.57, 52.83, 69.61, 79.72, 170.50; IR
(neat) 2970, 1740, 1430, 1260, 1050 cm-1; MS (FAB) 271 (MH, 100),
239 (8), 145 (14), 71 (14); Anal. Calcd for C7H11IO3: C, 31.13; H,
4.11. Found: C, 30.78; H, 4.18.
Methyl (2S*, 3R*)-2-Phenylseleno-3-methoxy-3-phenylpropanoate
(40). This material was prepared from cis methyl cinnamate using the
1
method described above for compound 37 (93%). Colorless oil; H
NMR (400 MHz, CDCl3) δ 3.24 (s, 3H), 3.27 (s, 3H), 4.11 (d, J ) 9.6
Hz, 1H), 4.49 (d, J ) 9.6 Hz, 1H), 7.35-7.27 (m, 8H), 7.67-7.64 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 50.58, 51.51, 56.86, 82.45, 127.33,
127.44, 128.36, 128.52, 128.70, 136.37, 138.50, 170.18; IR (neat) 2940,
2820, 1730, 1435, 1270, 1100 cm-1; MS (FAB) 350 (MH, 18), 319
(26), 121 (100); HRMS calcd for C17H18SeO3 (MH) 350.0421, found
350.0422.
General Procedure for the Allylation of r-Iodoesters under
Chelation Controlled Conditions. Compounds 7, 10, 13, 16, 19,
22, 25, 28, 31, and 34. To a suspension of MgBr2‚OEt2 (116 mg,
0.456 mmol) in CH2Cl2 (3 mL) at -78 °C was added dropwise a
solution of iodide 9 (146 mg, 0.456 mmol) in CH2Cl2 (1.5 mL).
Allyltrimethylsilane (0.145 mL, 0.912 mmol) and Et3B (0.09 mL of a
1.0 M solution in hexanes) were added to the mixture after stirring for
10 min at -78 °C. The resulting suspension was stirred for an
additional 3 h at this temperature, and then 0.2 equiv of Et3B were
added each hour until the reaction was judged to be complete by TLC.
The reaction mixture was then poured into a saturated NaHCO3 solution
and extracted with CH2Cl2. The combined organic extracts were
washed with brine, dried over MgSO4, filtered, and concentrated under
reduced pressure. The crude product was purified by flash chroma-
tography (CH2Cl2) to afford the anti product 10.
Methyl 2-[Propen-3-yl]-3-[((1,1-dimethylethyl)dimethylsilyl)oxy]-
3-phenylpropanoate (7 and 8). (Mixture of isomers). Colorless oil;
1H NMR (400 MHz, CDCl3) δ 7: -0.23 (s, 3H), -0.03 (s, 3H), 0.88
(s, 9H), 2.41-2.57 (m, 2H), 2.70-2.76 (m, 1H), 3.45 (s, 3H), 4.82 (d,
J ) 7.5 Hz, 1H), 4.95-5.03 (m, 2H), 5.69-5.79 (m, 1H), 7.21-7.33
(m, 5H), 8: -0.31 (s, 3H), -0.02 (s, 3H), 0.80 (s, 9H), 2.41-2.57 (m,
2H), 2.70-2.76 (m, 1H), 3.70 (s, 3H), 4.73 (d, J ) 9 Hz, 1H), 4.95-
5.05 (m, 2H), 5.69-5.79 (m, 1H), 7.21-7.33 (m, 5H); 13C NMR (50.3
MHz, CDCl3) δ 7: -5.32, -4.71, 18.00, 25.64, 32.53, 51.04, 55.51,
75.74, 116.25, 126.39, 127.44, 127.88, 135.69, 142.67, 173.24, 8:
-5.56, -4.80, 17.96, 25.44, 33.20, 51.21, 75.74, 116.48, 127.01,
128.13, 134.69, 142.08, 174.58; IR (neat) 2950, 2860, 1736, 1471, 1435,
1360, 1255, 1165, 1070, 1005 cm-1; MS (FAB) 335 (MH), 319, 277;
Anal. Calcd for C19H30SiO3: C, 68.22; H, 9.05. Found: C, 67.85; H,
9.17.
Methyl (2R*,3R*)-2-Bromo-3-methoxy-3-phenylpropanoate (36).15
This material was prepared from methyl cinnamate using a procedure
similar to that described above for compound 9.
Methyl (2R*,3R*)-2-Phenylseleno-3-methoxy-3-phenylpropanoate
(37). To a solution of PhSeBr (2.04 g, 8.66 mmol) and methyl
cinnamate (1.08 g, 6.66 mmol) in MeOH (30 mL) was added AgOTf
(2.22 g, 8.66 mmol). After stirring at room temperature for 30 min,
additional PhSeBr (0.31 g, 1.31 mmol) and AgOTf (0.34 g, 1.31 mmol)
were added. The mixture was stirred at room temperature for 30 min
at which time the reaction was judged to be complete by TLC.
Filtration through Celite and evaporation of the solvent left a residue
which was dissolved in EtOAc and washed with water and brine. The
organic phase was collected and dried over MgSO4. Flash chroma-
tography (10% EtOAc in hexanes) afforded the pure selenide as a white
solid. Mp 73-76 °C; 1H NMR (200 MHz, CDCl3) δ 7.4-7.1 (m, 10
H), 4.54 (d, J ) 10.5 Hz, 1H), 3.86 (d, J ) 10.5 Hz, 1H), 3.63 (s, 3H),
3.16 (s, 3H); 13C NMR (50.3 MHz, CDCl3) δ 50.23, 52.12, 57.12, 84.02,
127.77, 128.07, 128.24, 128.36, 128.59, 128.75, 135.51, 137.70, 171.97;
IR (KBr) 3040, 2960, 1730, 1470, 1460, 1430, 1420, 1370, 1350, 1320,
1310, 1280, 1210 cm-1; MS (EI) 350 (MH+), 317 (M-32); Anal. Calcd
for C17H18O3Se: C, 58.28; H, 5.18. Found: C, 58.01; H, 5.08.
Methyl (2S*, 3R*)-2-Iodo-3-methoxy-3-phenylpropanoate (38).
A solution of iodide 9 (691 mg, 2.16 mmol) and LiI‚3H2O (2.84 g,
15.1 mmol) in THF (30 mL) was refluxed overnight. The mixture
Methyl (2S*, 3R*)-2-[Propen-3-yl]-3-methoxy-3-phenylpropanoate
(10). Colorless oil; 1H NMR (200 MHz, CDCl3) δ 1.75-1.87 (m, 1H),
2.05-2.22 (m, 1H), 2.73-2.86 (m, 1H), 3.13 (s, 3H), 3.73 (s, 3H),4.26
(d, J ) 9.9 Hz, 1H), 4.89-5.02 (m, 2H), 5.48-5.68 (m, 1H), 7.26-

12534 J. Am. Chem. Soc., Vol. 118, No. 50, 1996
Guindon et al.
7.42 (m, 5H); 13C NMR (50.3 MHz, CDCl3) δ 33.34, 51.56, 52.99,
56.76, 84.99, 116.86, 127.66, 128.37, 128.52, 134.44, 138.81, 174.44;
IR (neat) 2980, 1740, 1650, 1440, 1170, 1100, 790 cm-1; MS (FAB)
235, 202 (10), 171 (15), 143 (20), 121 (100); HRMS calcd for C14H19O3
(MH) 235.1334, found 235.1341; Anal. Calcd for C14H18O3: C, 71.77;
H, 7.74. Found: C, 71.50; H, 7.68.
Methyl (2S*, 3R*)-2-[Propen-3-yl]-3-methoxybutanoate (13).
Colorless oil; 1H NMR (200 MHz, CDCl3) δ 1.14 (d, J ) 6.2 Hz, 3H),
2.20-2.28 (m, 1H), 2.30-2.38 (m, 1H), 2.58 (ddd, J ) 5.6, 7.6, 8.8
Hz, 1H), 3.29 (s, 3H), 3.50 (dd, J ) 6.2, 7.6 Hz, 1H), 3.66 (s, 3H),
4.96-5.09 (m, 2H), 5.62-5.82 (m, 1H); 13C NMR (50.3 MHz, CDCl3)
δ 16.19, 32.17, 51.45, 51.54, 56.62, 77.44, 116.73, 135.13, 174.20; IR
(neat) 2840, 1735, 1640, 1435, 1375, 1100, 990 cm-1; MS (FAB) 249
(MH + C3H8S, 100), 173 (MH, 40), 141 (39), 127 (16), 115 (32);
HRMS calcd for C9H17O3 (MH) 173.1178, found 173.1170.
2920, 2800, 1720, 1415, 1140, 1065 cm-1; MS (FAB) 199 (MH, 100),
185 (19), 167 (47), 137 (35); HRMS calcd for C11H21O3 (MH) 199.1334,
found 199.1323.
Methyl (2S*, 3R*)-3-[Tetrahydrofuran-2-yl]-2-[propen-3-yl]-pro-
1
panoate (34). Colorless oil; H NMR (400 MHz, CDCl3) δ 1.51-
1.59 (m, 1H), 1.80-1.93 (m, 2H), 1.98-2.05 (m, 1H), 2.16-2.22 (m,
1H), 2.30-2.37 (m, 1H), 2.47-2.55 (m, 1H), 3.68 (s, 3H), 3.71-3.76
(m, 1H), 3.80-3.88 (m, 1H), 3.97-4.02 (m, 1H), 4.97-5.09 (m, 2H),
5.65-5.77 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 25.45, 29.52, 33.31,
51.20, 51.43, 67.91, 79.66, 116.72, 134.70, 174.20; IR (neat) 2950,
2880, 1745, 1440, 1200, 1170, 1070 cm-1; MS 185 (MH, 2), 143 (12),
111 (7), 71 (100); HRMS calcd for C10H17O3 (MH) 185.1178, found
185.1167.
Methyl (2S*, 3R*)-2-[2-Phenylselenyl-3-trimethylsilylpropanyl]-
3-methoxy-3-phenylpropanoate (57). To a suspension of MgBr2‚OEt2
(51.6 mg, 0.20 mmol) in CH2Cl2 (1 mL) at -78 °C was added dropwise
a solution of phenylselenide 37 (54.5 mg, 0.20 mmol) in CH2Cl2 (1
mL). Allyltrimethylsilane (0.065 mL, 0.40 mmol) and Et3B (0.04 mL
of a 1.0 M solution in hexanes) were added to the mixture after stirring
for 10 min at -78 °C. The resulting suspension was stirred for an
additional 6 h at this temperature, and then 0.2 equiv of Et3B were
added each hour until the reaction was judged to be complete by TLC.
The reaction mixture was then poured into saturated NaHCO3 and
extracted with CH2Cl2. The combined organic extracts were washed
with brine, dried over MgSO4, filtered, and concentrated under reduced
pressure. The crude product was carefully purified by flash chroma-
tography (CH2Cl2) using silica neutralized with Et3N to afford the anti
product 57 (46.4 mg, 50%). Colorless oil; 1H NMR (300 MHz, CDCl3)
δ -0.04 (s, 9H), 0.74 (dd, J ) 9.9, 9.9 Hz, 1H), 1.08 (dd, J ) 4.8, 4.8
Hz, 1H), 1.22 (m, 1H), 1.79 (m, 1H), 3.87-3.96 (m, 1H), 3.14 (s, 3H),
3.32 (td, J ) 3.0, 9.8 Hz, 1H), 3.75 (s, 3H), 4.23 (d, J ) 9.8 Hz, 1H),
7.10-7.40 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 26.34, 36.62,
40.21, 51.60, 52.08, 56.68, 85.07, 127.48, 127.72, 128.24, 128.48,
134.34, 136.10, 138.78, 174.83; IR (neat) 3060, 2950, 1732, 1580, 1435,
1370, 1250, 1165, 845 cm-1; MS (FAB) 463.3 (MH, 8), 433.3 (94),
307.4 (46), 275 (36), 143 (80), 121 (100); HRMS calcd for C23H33O3-
SeSi (MH) 464.1286, found 464.1309.
Methyl (2S*, 3R*)-2-Propyl-3-methoxy-3-phenylpropanoate (58).
To a suspension of MgBr2‚OEt2 (194 mg, 0.75 mmol) in CH2Cl2 (5
mL) at -78 °C was added dropwise a solution of bromide 36 (202
mg, 0.738 mmol) in CH2Cl2 (1.5 mL). Allyltrimethylsilane (0.235 mL,
1.48 mmol) and Et3B (0.150 mL of a 1.0 M solution in hexanes) were
added to the mixture after stirring for 10 min at -78 °C. The resulting
suspension was stirred for an additional 1.5 h at this temperature, and
then tributyltin hydride (0.20 mL, 0.75 mmol) was added to the reaction
mixture. Subsequently 0.2 equiv of Et3B were added each hour until
the reaction was judged to be complete by TLC. The reaction mixture
was then poured into saturated NaHCO3 and extracted with CH2Cl2.
The combined organic extracts were washed with brine, dried over
MgSO4, filtered, and concentrated under reduced pressure. The crude
product was purified by flash chromatography (CH2Cl2) to afford the
anti product (87.8 mg, 39%). Colorless oil; 1H NMR (300 MHz,
CDCl3) δ -0.12 (s, 9H), 0.27-0.38 (m, 2H), 0.96-1.17 (m, 3H), 1.46-
1.55 (m, 1H), 2.68-2.78 (m, 1H), 3.13 (s, 3H), 3.77 (s, 3H), 4.23 (d,
J ) 10 Hz, 1H), 7.29-7.40 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
16.18, 21.47, 32.63, 51.48, 52.96, 56.60, 85.46, 127.57, 128.13, 128.35,
139.09, 175.39; IR (neat) 3028, 2950, 1739, 1494, 1248, 1164, 1103
cm-1; MS (FAB) 308.9 (MH, 29), 276.9 (35), 145 (71), 121 (100);
HRMS calcd for C17H29O3Si (MH) 309.1886, found 309.1869; Anal.
Calcd for C17H20O3Si: C, 66.19; H, 9.15. Found: C, 66.42; H, 8.88.
Methyl (2S*, 3R*)-2-[Propen-3-yl]-3-methoxy-3-cyclohexylpro-
1
panoate (16). Colorless oil; H NMR (200 MHz, CDCl3) δ 1.13-
1.28 (m, 5H), 1.47 (s, 1H), 1.65-1.72 (m, 5H), 2.17-2.25 (m, 1H),
2.30-2.38 (m, 1H), 2.71 (ddd, J ) 5.0, 7.9, 9.7 Hz, 1H), 3.16 (s, 3H),
3.67 (s, 3H), 5.00 (d, J ) 10.1 Hz, 1H), 5.06 (m, 2H), 5.73 (m, 1H);
13C NMR (50.3 MHz, CDCl3) δ 26.20, 26.41, 26.58, 30.45, 33.29,
40.50, 48.11, 51.42, 61.06, 86.72, 116.77, 135.17, 174.60; IR (neat)
2920, 1740, 1440, 1170, 1110 cm-1; MS (CI,CH4) 241 (MH+, 53),
209 (100), 177 (27), 149 (49), 127 (21); HRMS calcd for C14H25O3
(MH) 241.1804, found 241.1794.
Methyl (2S*, 3R*)-2-[Propen-3-yl]-3-methoxy-4-methylpen-
tanoate (19). Colorless oil; 1H NMR (200 MHz, CDCl3) δ 0.89 (d, J
) 6.8 Hz, 3H), 0.99 (d, J ) 6.8 Hz, 3H), 1.86 (m, 1H), 2.16-2.24 (m,
1H), 2.31-2.39 (m, 1H), 2.64 (ddd, J ) 5.0, 8.1, 9.7 Hz, 1H), 3.20
(dd, J ) 3.9, 8.1 Hz, 1H), 3.40 (s, 3H), 4.15 (q, J ) 7.1 Hz, 2H),
4.97-5.10 (m, 2H), 5.64-5.80 (m, 1H); 13C NMR (50.3 MHz, CDCl3)
δ 14.31, 16.04, 20.18, 30.16, 33.37, 48.84, 60.21, 61.11, 86.92, 116.75,
135.10, 174.10; IR (neat) 2980, 1740, 1650, 1470, 1380, 1180, 1100,
920 cm-1; MS (CI, CH4) 215 (MH+, 81), 197 (18), 183 (95), 169 (70),
149 (23), 137 (29), 129 (20), 109 (100); HRMS calcd for C11H21O3
(MH) 201.1491, found 201.1495.
Methyl (2S*, 3R*)-2-[Propen-3-yl]-2-methyl-3-methoxy-3-phen-
ylpropanoate (22). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.04
(s, 3H), 1.72 (dd, J ) 7.6, 13.3 Hz, 1H), 2.45 (dd, J ) 7.0, 13.5 Hz,
1H), 3.16 (s, 3H), 3.71 (s, 3H), 4.48 (s, 1H), 4.92-5.00 (m, 2H), 5.54-
5.60 (m, 1H), 7.25-7.35 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
14.85, 41.10, 51.62, 52.06, 57.18, 88.00, 118.16, 127.78, 128.43, 133.12,
137.04, 175.70; IR (neat) 2980, 2840, 1745, 1460, 1220, 1100, 940
cm-1; MS (FAB) 249 (MH, 12), 217 (10), 189 (8), 157 (43), 121 (100);
HRMS calcd for C15H21O3 (MH) 249.1491, found 249.1503.
Methyl (2S*, 3R*)-2-[Propen-3-yl]-2-methyl-3-methoxybutanoate
1
(25). Colorless oil; H NMR (400 MHz, CDCl3) δ 1.10 (d, J ) 6.3
Hz, 3H), 1.12 (s, 3H), 1.28 (t, J ) 7.1 Hz, 3H), 2.04 (dd, J ) 7.5, 13.5
Hz, 1H), 2.34 (dd, J ) 7.1, 13.5 Hz, 1H), 3.31 (s, 3H), 3.60 (q, J )
6.3 Hz, 1H), 4.12-4.22 (m, 2H), 5.03-5.08 (m, 2H), 5.65-5.75 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 12.54, 14.16, 15.04, 40.70, 56.94,
60.10, 81.03, 117.78, 133.53, 175.17; IR (neat) 2983, 2937, 1723, 1464,
1383, 1236 cm-1; MS (FAB) 201 (MH, 100), 169 (83), 141 (37), 132
(87), 129 (37); HRMS calcd for C11H21O3 (MH) 201.1491, found
201.1499.
Methyl (2S*, 3R*)-2-[Propen-3-yl]-2, 4-dimethyl-3-methoxypen-
1
tanoate (28). Colorless oil; H NMR (400 MHz, CDCl3) δ 1.02 (t, J
) 7.4 Hz, 3H), 1.10 (s, 3H), 1.26 (t, J ) 7.1 Hz, 3H), 1.38-1.55 (m,
2H), 2.05 (dd, J ) 7.5, 13.5 Hz, 1H), 2.38 (dd, J ) 7.1, 13.3 Hz, 1H),
3.30-3.34 (m, 1H), 3.40 (s, 3H), 4.10-4.17 (m, 2H), 5.00-5.05 (m,
2H), 5.64-5.71 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 11.66, 14.16,
16.04, 23.70, 40.48, 51.14, 60.14, 60.87, 88.06, 117.73, 133.74, 175.36;
IR (neat) 2980, 2810, 1720, 1450, 1210, 1090 cm-1; MS (FAB) 215
(MH, 100), 183 (37), 169 (33), 109 (53); HRMS calcd for C12H23O3
(MH) 215.1647, found 215.1633; Anal. Calcd for C12H22O3: C, 67.26;
H, 10.35. Found: C, 67.12; H, 10.13.
Methyl (2S*, 3R*)-3-[Tetrahydropyran-2-yl]-2-[propen-3-yl]-
propanoate (31). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.27-
1.37 (m, 1H), 1.46-1.61 (m, 3H), 1.67-1.76 (m, 1H), 1.84-1.89 (m,
1H), 2.27-2.33 (m, 1H), 2.37-2.41 (m, 1H), 2.50-2.58 (m, 1H), 3.36-
3.51 (m, 2H), 3.69 (s, 3H), 3.93-3.99 (m, 1H), 4.99-5.11 (m, 2H),
5.69-5.77 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 23.08, 25.64, 28.88,
32.16, 51.08, 51.42, 68.46, 78.18, 116.51, 134.81, 174.21; IR (neat)
General Procedure for the Allylation of r-Iodoesters. Com-
pounds 11, 14, 17, 20, 23, 26, 29, 32, and 35: To a solution of iodide
9 (83.2 mg, 0.259 mmol) in CH2Cl2 (2.5 mL) at -78 °C were added
allyltributyltin (0.08 mL, 0.52 mmol) and Et3B (55 µL of a 1.0 M
solution in hexanes). The reaction mixture was then stirred for an
additional 3 h at this temperature. After concentration, the residue was
purified by flash chromatography (CH2Cl2) to afford the desired syn
adduct 11.
Methyl (2R*,3R*)-2-[Propen-3-yl]-3-methoxy-3-phenylpropanoate
(11). Colorless oil; 1H NMR (200 MHz, CDCl3) δ 2.46-2.52 (m, 1H),
2.61-2.68 (m, 1H), 2.81 (ddd, J ) 3.8, 8.4, 10.1 Hz, 1H), 3.19 (s,
3H), 3.40 (s, 3H), 4.27 (d, J ) 8.6 Hz, 1H), 4.97-5.11 (m, 2H), 5.66-
5.78 (m, 1H), 7.25-7.37 (m, 5H); 13C NMR (50.3 MHz, CDCl3) δ

C-C Bond Forming Reactions of â-Alkoxy Esters
J. Am. Chem. Soc., Vol. 118, No. 50, 1996 12535
33.10, 50.88, 53.38, 56.52, 83.58, 116.40, 126.97, 127.79, 127.87,
128.02, 135.09, 139.16, 172.69; IR (neat) 3000, 1740, 1650, 1450, 1180,
1110, 790 cm-1; MS (CI, CH4): 235 (MH+, 4), 203 (45), 143 (100),
121 (22); HRMS calcd for C14H19O3 (MH) 235.1334, found 235.1323.
Methyl (2R*,3R*)-2-[Propen-3-yl]-3-methoxybutanoate (14). Col-
(m, 1H), 4.98-5.10 (m, 2H), 5.68-5.80 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 23.12, 25.79, 29.41, 32.87, 51.28, 51.51, 68.64, 77.62, 116.39,
135.40, 173.87; IR (neat) 2900, 2800, 1720, 1420, 1070 cm-1; MS
(FAB) 199 (MH, 100), 171 (29), 167 (51), 137 (34); HRMS calcd for
C11H19O3 (MH) 199.1334, found 199.1342.
1
orless oil; H NMR (200 MHz, CDCl3) δ 1.09 (d, J ) 6.2 Hz, 3H),
Methyl (2R*,3R*)-3-[Tetrahydrofuran-2-yl]-2-[propen-3-yl]pro-
1
2.35-2.40 (m, 1H), 2.39-2.45 (m, 1H), 2.54 (ddd, J ) 5.2, 7.3, 9.1
Hz, 1H), 3.27 (s, 3H), 3.38 (dd, J ) 6.2, 7.3 Hz, 1H), 3.60 (s, 3H),
4.89-5.03 (m, 2H), 5.57-5.78 (m, 1H); 13C NMR (50.3 MHz, CDCl3)
δ 16.49, 32.95, 51.17, 51.31, 56.41, 77.07, 116.43, 135.35, 173.73; IR
(neat) 2980, 1740, 1650, 1440, 1385, 1135, 1105, 920 cm-1; MS (CI,
CH4) 173 (MH+,45), 141 (100); HRMS calcd for C9H17O3 (MH)+
173.1178, found 173.1168.
panoate (35). Colorless oil; H NMR (400 MHz, CDCl3) δ 1.64-
1.73 (m, 1H), 1.83-2.00 (m, 3H), 2.37-2.43 (m, 1H), 2.42-2.51 (m,
1H), 2.54-2.62 (m, 1H), 3.66 (s, 3H), 3.71-3.86 (m, 2H), 3.93-4.00
(m, 1H), 4.99-5.11 (m, 2H), 5.70-5.81 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 25.50, 29.25, 33.83, 50.67, 51.38, 67.90, 79.04, 116.54,
135.18, 173.74; IR (neat) 2960, 2880, 1440, 1070 cm-1; MS (FAB)
185 (MH, 100), 152 (41), 143 (8), 71 (28); HRMS calcd for C10H17O3
(MH) 185.1178, found 185.1175.
Methyl (2R*,3R*)-2-[Propen-3-yl]-3-methoxy-3-cyclohexylpro-
1
panoate (17). Colorless oil; H NMR (200 MHz, CDCl3) δ 0.99-
Proof of Stereochemistry for Compound 14. To a solution of
alcohol 4317 (56.0 mg, 0.354 mmol) and Proton Sponge (759 mg, 3.54
mmol) in CH2Cl2 (1 mL) at 25 °C was added methyl triflate (400 µL,
3.54 mmol). When TLC indicated that the reaction was complete, the
solution was diluted with ether, washed successively with water, 10%
HCl, water, and brine, and dried (MgSO4). Flash chromatography
afforded the desired methyl ether (36.3 mg, 59%). The NMR spectrum
of this compound was identical to that obtained for adduct 14. 1H
NMR (200 MHz, CDCl3) δ 1.09 (d, J ) 6.2 Hz, 3H), 2.22-2.44 (m,
2H), 2.54 (ddd, J ) 5.2, 7.3,9.1 Hz, 1H), 3.27 (s,3H), 3.38 (dd, J )
6.2,7.3 Hz, 1H), 3.60 (s, 3H), 4.89-5.03 (m, 2H), 5.57-5.78 (m, 1H).
Proof of Stereochemistry for Compounds 25 and 26. A 1.34 M
solution of Me2BBr (620 µL, 2 equiv) in CH2Cl2 was added dropwise
to a cold (0 °C) solution of compound 25 in CH2Cl2 (129 mg, 0.64
mmol) and triethylamine (20 µL, 0.2 equiv). The resulting mixture
was stirred at 0 °C for 10 min and for 3 h at room temperature until
reaction completion and then the mixture was poured into a solution
of NH4Cl:NH4OH (4:1), diluted with EtOAc, and stirred at room
temperature for 15 min. Brine was added, the phases were separated,
and the aqueous layer was extracted with EtOAc. The combined
organic extracts were washed with brine, dried (MgSO4), filtered, and
concentrated to afford â-hydroxyester 44 (65.6 mg, 55%) after
purification by flash chromatography. The NMR spectrum of this
compound was identical to that previously reported.17 1H NMR (400
MHz, CDCl3) δ 1.10 (s, 3H), 1.12 (d, J ) 6.5 Hz, 3H), 1.25 (t, J ) 7.1
Hz, 3H), 2.23-2.29 (dd, J ) 7.4 and 13.7 Hz, 1H), 2.38-2.43 (dd, J
) 7.4 and 13.7 Hz, 1H), 2.64 (bs, 1H, OH), 3.83-3.87 (q, J ) 6.5 Hz,
1H), 4.12-4.18 (q, J ) 7.1 Hz, 2H), 5.02-5.07 (m, 2H), 5.65-5.72
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.11, 16.90, 17.58, 40.86,
50.88, 60.56, 71.14, 118.11, 133.31, 176.49; IR (neat) 3700-3300,
1.27 (m, 6H), 1.61-1.82 (m, 5H), 2.37-2.42 (m, 1H), 2.42-2.48 (m,
1H), 2.66 (ddd, J ) 5.6, 7.2, 8.8 Hz, 1H), 3.40 (s, 3H), 3.65 (s, 3H),
4.97 (dd, J ) 1.6, 10.1 Hz, 1H), 5.05 (m, 2H), 5.76 (m, 1H); 13C NMR
(50.3 MHz, CDCl3) δ 26.21, 26.35, 27.32, 30.10, 32.24, 41.74, 48.74,
48.42, 51.39, 61.22, 86.73, 116.27, 135.98, 174.65; IR (neat) 2920,
1740, 1450, 1160, 1100 cm-1; MS (CI, CH4) 241 (MH+, 100), 177
(33), 149 (54), 127 (18); HRMS calcd for C14H25O3 (MH) 241.1804,
found 241.1817.
Methyl (2R*,3R*)-2-[Propen-3-yl]-3-methoxy-4-methylpentanoate
1
(20). Colorless oil; H NMR (200 MHz, CDCl3) δ 0.92 (d, J ) 6.8
Hz, 3H), 0.97 (d, J ) 6.8 Hz, 3H), 1.24 (t, J ) 7.1 Hz, 3H), 1.65-
1.75 (m, 1H), 2.37-2.42 (m, 1H), 2.43-2.49 (m, 1H), 2.55-2.66 (m,
1H), 3.19 (dd, J ) 4.2, 7.7 Hz, 1H), 3.44 (s, 3H), 4.12 (q, J ) 7.1 Hz,
2H), 5.01-5.11 (m, 2H), 5.67-5.84 (m, 1H); 13C NMR (50.3 MHz,
CDCl3) δ 14.17, 16.49, 19.95, 31.55, 32.73, 49.23, 60.16, 61.33, 86.97,
116.28, 135.87, 174.03; IR (neat) 2980, 1740, 1650, 1475, 1380, 1160,
1100, 920 cm-1; MS (CI, CH4) 215 (MH+, 59), 183 (100), 169 (48),
137 (24), 109 (78), 87 (30); HRMS calcd for C11H21O3 (MH) 201.1491,
found 201.1497; Anal. Calcd for C11H20O3: C, 65.95; H, 10.07.
Found: C, 65.49; H, 9.66.
Methyl (2R*,3R*)-2-[Propen-3-yl]-2-methyl-3-methoxy-3-phenyl-
1
propanoate (23). Colorless oil; H NMR (200 MHz, CDCl3) δ 1.04
(s, 3H), 2.30 (dd, J ) 7.9, 13.6 Hz, 1H), 2.67 (dd, J ) 6.8, 13.6 Hz,
1H), 3.21 (s, 3H), 3.61 (s, 3H), 4.45 (s, 1H), 4.99-5.08 (m, 2H), 5.65-
5.86 (m, 1H), 7.20-7.37 (m, 5H); 13C NMR (50.3 MHz, CDCl3) δ
16.04, 40.54, 51.38, 52.44, 57.41, 87.48, 117.79, 127.74, 127.83, 128.05,
134.58, 137.79, 175.08; IR (neat) 3000, 2960, 1750, 1650, 1460, 1290,
1235, 1105, 920 cm-1; MS (CI, CH4) 249 (MH+, 19), 217 (80), 212
(15), 185 (9), 175 (10), 157 (100), 130 (9), 121 (41); HRMS calcd for
C11H21O3 (MH) 201.1491, found 201.1497; Anal. Calcd for
C15H20O3: C, 72.55; H, 8.12. Found: C, 72.50; H, 8.02.
3000, 2960, 1725, 1640, 1380, 1300, 1230, 1150, 1090, 920 cm-1
;
MS (FAB) 187(MH,100), 169(22), 154(23), 137(26), 123(16); HRMS
calcd for C10H19O3 (MH) 187.13342, found 187.13390. The â-hy-
droxyester 45 was obtained in a similar manner from compound 26.
The NMR spectrum of this compound was identical to that previously
reported.17 1H NMR (400 MHz, CDCl3) δ 1.13 (s, 3H), 1.15 (d, J )
6.4 Hz, 3H), 1.26 (t, J ) 7.1 Hz, 3H), 2.22-2.27 (dd + bs, J ) 7.8
and 13.8 Hz, 2H), 2.49-2.54 (dd, J ) 7.0 and 13.8 Hz, 1H), 3.88-
3.93 (q, J ) 6.4 Hz, 1H), 4.12-4.17 (q, J ) 7.1 Hz, 2H), 5.04-5.10
(m, 2H), 5.74-5.81 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.12,
17.24, 18.16, 39.62, 50.60, 60.56, 71.80, 117.91, 134.09, 176.12; IR
Methyl (2R*,3R*)-2-[Propen-3-yl]-2-methyl-3-methoxybutanoate
1
(26). Colorless oil; H NMR (400 MHz, CDCl3) δ 1.07 (d, J ) 6.4
Hz, 3H), 1.08 (s, 3H), 1.25 (t, J ) 7.1 Hz, 3H), 2.31 (dd, J ) 6.7, 13.7
Hz, 1H), 2.49 (dd, J ) 6.8, 13.8 Hz, 1H), 3.33 (s, 3H), 3.50 (q, J )
6.2 Hz, 1H), 4.12 (q, J ) 7.1 Hz, 2H), 5.01-5.07 (m, 2H), 5.70-5.77
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 13.86, 14.13, 15.32, 40.90,
51.19, 57.22, 60.19, 80.53, 117.53, 134.35, 175.11; IR (neat) 2928,
2856, 1718, 1602, 1465, 1380 cm-1; MS (CI, CH4) 155 (M - OC2H5,
31), 142 (47), 113 (21), 95 (34), 59 (100); HRMS calcd for C9H16O2
(M - OC2H5) 155.1072, found 155.1072.
(neat) 3700-3200, 3000, 1720, 1640, 1460, 1380, 1220, 920 cm-1
;
Methyl (2R*,3R*)-2-[Propen-3-yl]-2, 4-dimethyl-3-methoxypen-
MS (FAB) 187(MH,100), 169(20), 154(18), 137(21), 123(17); HRMS
calcd for C10H19O3 (MH) 187.1334, found 187.1337.
1
tanoate (29). Colorless oil; H NMR (400 MHz, CDCl3) δ 0.98 (t, J
) 7.4 Hz, 3H), 1.06 (s, 3H), 1.24 (t, J ) 7.1 Hz, 3H), 1.28-1.36 (m,
1H), 1.45-1.55 (m, 1H), 2.30 (dd, J ) 6.7, 13.6 Hz, 1H), 2.50 (dd, J
) 6.8, 13.6 Hz, 1H), 3.26-3.31 (m, 1H), 3.48 (s, 3H), 4.11 (q, J )
7.1 Hz, 2H), 5.01-5.07 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 11.58,
14.12, 15.11, 25.09, 41.40, 52.87, 60.16, 61.28, 87.94, 117.69, 134.13,
175.11; IR (neat) 2980, 1735, 1460, 1100, 920 cm-1; MS (FAB) 215
(MH, 100), 183 (29), 154 (89), 137 (95), 123 (50); HRMS calcd for
C10H17O2 (M - OC2H5) 169.1229, found 169.1223.
Acknowledgment. Thanks to Dr. Anne-Marie Faucher for
assistance during the preparation of this mauscript.
Supporting Information Available: General experimental
procedures and spectral data for compounds 47 and 49, NMR
spectra for those compounds for which elemental analysis is
not available, and tables of NMR chemical shift correlations
for allylated products (32 pages). See any current masthead
page for ordering and Internet access instructions.
Methyl (2R*,3R*)-3-[Tetrahydropyran-2-yl]-2-[propen-3-yl]pro-
1
panoate (32). Colorless oil; H NMR (400 MHz, CDCl3) δ 1.34-
1.57 (m, 5H), 1.81-1.87 (m, 1H), 2.20-2.26 (m, 1H), 2.28-2.35 (m,
1H), 2.34-2.50 (m, 1H) 3.38-3.45 (m, 2H), 3.67 (s, 3H), 3.97-4.02
JA9541241