Diastereoselective allylations of allyl-propargyl hybrid cations: Synthesis of conjugated 1,5-dien-7-yne frameworks bearing C(4)-stereogenic centers

Article abstract of DOI:10.1021/ol049847g

Chiral C(4)-substituted (E)- or (Z)-1-alkynyl-1-trimethylsilyloxy-2-butene systems provide anti-(Z) or syn-(Z) conjugated dienyne, with a very high level of stereocontrol, on treatment with BF₃·OEt₂ in CH₂Cl₂ at

Full text of DOI:10.1021/ol049847g

ORGANIC
LETTERS
2004
Vol. 6, No. 9
1369-1372
Diastereoselective Allylations of
Allyl−Propargyl Hybrid Cations:
Synthesis of Conjugated 1,5-Dien-7-yne
Frameworks Bearing C(4)-Stereogenic
Centers
,†
,‡
Teruhiko Ishikawa,* Toshiaki Aikawa,‡ Yumiko Mori,‡ and Seiki Saito*
Department of Bioscience and Biotechnology, School of Engineering and School of
Education, Okayama UniVersity, Tsushima, Okayama, Japan 700-8530
seisaito@biotech.okayama-u.ac.jp
Received January 27, 2004
ABSTRACT
Chiral C(4)-substituted (E)- or (Z)-1-alkynyl-1-trimethylsilyloxy-2-butene systems provide anti-(Z) or syn-(Z) conjugated dienyne, with a very
high level of stereocontrol, on treatment with BF3‚OEt2 in CH Cl2 at −50 °C in the presence of allyltrimethylsilane. The Cieplak conformation
2
for (E)-substrates and neighboring-group participation for (Z)-substrates are considered to be responsible for the stereochemical consequences.
Lewis acid-promoted nucleophilic allylations using allylsi-
lanes have found widespread application in organic synthe-
sis.1 Among them, cyclic acetal-based oxonium ions have
succeeded in allylation with a high level of diastereocontrol,
for which general stereoelectronic models2 have been pro-
posed. On the other hand, no stereoselective allylation of
acyclic allylic cations has been reported so far.3 Fortunately,
a clue that deserves consideration about such a synthetically
meaningful system has recently been provided which features
the intervention of an allyl-propargyl hybrid cation (I1)
generated from 1-(alkynyl)propen-2-yl silyl ethers (A) by
the action of Lewis acid (Scheme 1).4 The subsequent
Scheme 1
† School of Education.
‡ School of Engineering.
(1) For reviews for allylation using allyltrimethylsilane, see: (a) Hosomi,
A. Acc. Chem. Res. 1988, 21, 200-206. (b) Sakurai, H. Pure Appl. Chem.
1985, 57, 1759-1770. (c) Yanagisawa, A. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto H., Eds.; Springer-
Verlag: Berlin, Heidelberg, 1999; Vol. II, Chapter 27.
(2) (a) Schmitt, A.; Ressig, H.-U. Synlett 1990, 40-42. (b) Powell, S.
A.; Tenenbaum, J. M.; Woerpel, K. A. J. Am. Chem. Soc. 2002, 124,
12648-12649. (c) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Woerpel,
K. A. J. Am. Chem. Soc. 1999, 121, 12208-12209. (d) Kudo, K.;
Hashimoto, Y.; Sukegawa, M.; Hasegawa, M.; Saigo, K. J. Org. Chem.
1993, 58, 579-587.
allylation with allyltrimethylsilane proceeded in a totally
regioselective manner to furnish dienynes involving conju-
10.1021/ol049847g CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/31/2004

gated (Z)-enyne functionality (B). Thus, if the substituent R
involves a stereogenic center as in 1 or 2, the allylation may
proceed in a diastereomerically biased manner. If realized,
this may provide a useful way for synthesizing chiral
conjugated 1,5-dien-7-yne backbones with new C(4)-stereo-
genic centers such as 3 or 4.
This idea led to fruitful results which are summarized in
Table 1: BF3‚OEt2-promoted allylations of 1a-j or 5 (E-
Figure 1.
Table 1. Diastereoselective Allylation of (E)- and
(Z)-Substratesa
The level of diastereoselectivity seems to be controlled
by the steric bulkiness of R1, showing the highest ratio >99:1
when R1 ) i-Pr for both E- and Z-isomers (entries 5, 7-9,
and 12). For entries 7-10, 12, and 13, a high level of control
was simultaneously achieved over not only two contiguous
stereogenic centers but also the geometry of the conjugated
enyne moieties.6 It should be noted that mixtures of diaste-
reoisomers of 1:1 to 3:1 ratios with regard to the propargylic
stereogenic centers were used as substrates in these cases.
Furthermore, each diastereoisomer isolated from such a
mixture by a silica gel column chromatography led to the
same product as that obtained from the mixture of propargylic
epimers. These facts clearly suggest a typical SN1 nature of
the reaction and also the dominant role of the TBDMSO-
linked stereogenic center as a stereocontrol element. Al-
though entry 4 (1d) shows unacceptable selectivity (2.5:1),
entry 14, employing an acetonide protection (5), may provide
a practical replacement for it, giving anti- (6) and syn-isomer
(7) in a ratio of 5:1.
The choice of Lewis acids was highly important for the
reaction to be successful. Trimethylsilyl triflate (TMSOTf),
for instance, exhibited remarkable effects on not only
chemical yields but also syn/anti selectivity. Representative
examples are shown in Scheme 2. In general, TMSOTf
a Conditions: allyltrimethylsilane (150 mol %), BF3‚OEt2 (100 mol %),
CH2Cl2, -50 °C, 10 min. b 3c ) 3k, 4c ) 4k, 3h ) 3l, 4h ) 4l, 3j ) 3m,
c
4j ) 4m. Z/E ) 8/1.
Scheme 2. Effect of Lewis Acid on Diastereoselective
Allylation for Representative (E)- and (Z)-Isomersa
isomers) and 2k-m (Z-isomers) with allyltrimethylsilane
smoothly proceeded (CH2Cl2, -50 °C, 10 min) to afford anti-
(3a-j or 6) and syn-products (4k-m) in good yields,
respectively, depending on the geometry of the substrates.
Absolute configurations for induced stereogenic centers of
1
3 and 6 or 4 and 7 were determined by H NMR analysis
based on NOE data observed for tetrahydrofuran derivatives
8 or 9 derived from these products, respectively, via
deprotection and iodo-etherification (Figure 1).5
(3) For synthetically useful allylations of allyl, propargyl, or benzyl
cations with no stereochemical consequences, see: (a) Cella, J. A. J. Org.
Chem. 1982, 47, 2125-2130. (b) Mayr, H.; Pock, R. Tetrahedron 1986,
42, 4211-4214. (c) Murakami, M.; Kato, T.; Mukaiyama, T. Chem. Lett.
1987, 1167-1170. (d) Hayashi, M.; Inubushi, A.; Mukaiyama, T. Chem.
Lett. 1987, 1975-1978. (e) Mayr, H.; Gorath, G.; Bauer, B. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 788-789. (f) Yokozawa, T.; Furuhashi, K.;
Natsume, H. Tetrahedron Lett. 1995, 36, 5243-5246. (g) Kaur, G.; Kaushik,
M.; Trehan, S. Tetrahedron Lett. 1997, 38, 2521-2524. (h) Rubin, M.;
Gevorgyan, V. Org. Lett. 2001, 3, 2705-2707.
a Conditions: allyltrimethylsilane (150 mol %), Lewis acid (100
mol %), CH2Cl2, -50 °C, 10 min.
(4) Ishikawa, T.; Okano, M.; Aikawa, T.; Saito, S. J. Org. Chem. 2001,
66, 4635-4642: see also Ishikawa, T.; Aikawa, T.; Mori, Y.; Saito, S.
Org. Lett. 2003, 5, 51-54.
lowered chemical yields for both 1h and 2l. The syn/anti
selectivity was kept intact for (E)-isomer 1h irrespective of
1370
Org. Lett., Vol. 6, No. 9, 2004

Lewis acids, but for (Z)-isomer 2l, a reversal of the
stereochemical outcome was observed for TMSOTf (2:1 in
preference to anti-isomer 3l) in marked contrast to BF3‚OEt2
(>99% syn). These results strongly suggest that the steric
course for the (E)- and (Z)-substrates should be different from
each other,7 and the way by which the syn products result
from 2 might involve some dynamic process which is specific
for 2 and is lacking for 1 as is discussed later (vide infra).
three models (FAE1, FAE2, and CE2) may suffer from this
disadvantage. In addition, CE1 would expect stabilizing elec-
trostatic interaction stemming from the gauche-OCCC ar-
rangement.10 The ion-pairing with TfO- would not change
the situation for these models because such a non-nucleo-
philic counteranion should locate far away from both R1 and
Si′O substituents or from an incoming nucleophile.
On the other hand, it seems difficult to interpret the highly
syn-selective nature for allylation of (Z)-isomers (entries
11-13) on the basis of these four models (FAZ1, FAZ2, CZ1,
and CZ2). Every conformation seems to lack enough stabi-
lization to override the others. Therefore, as already men-
tioned above, the reaction should involve a certain dynamic
process in which the TBDMSO-linking stereogenic center
can act as a stereocontrolling element.
We tried to explain the selectivity observed for 1 and 2
on the basis of Felkin-Ahn models taking the Cieplak effect8
into account.9 Thus, as shown in Scheme 3, four models such
Scheme 3. Felkin-Ahn and Cieplak Stereochemical Models
The most plausible mechanism may involve the 1,5-
participation11 of the TBDMSO group by which BF3‚OEt2-
promoted ionization should be assisted. The outline of such
a process is illustrated in Scheme 4.
Scheme 4. Siloxy Participation Mechanism for (Z)-Substrates
as Felkin-Ahn (FAE1 and FAE2) and Cieplak (CE1 and CE2)
types for (E)-isomers and their (Z)-versions (FAZ1, FAZ2, CZ1,
and CZ2) deserve consideration.
The BF3‚OEt2-promoted and TBDMSO-participating ion-
ization may involve an entropically advantageous five-
membered transition state structure leading to two possible
cationic intermediates such as I2 and I3.12 Although the
energy difference between these two intermediates might be
small due to the small size of the alkynyl group, the R1 group
necessarily interferes with approach of allyltrimethylsilane
toward I3, whereas I2 may be free from such a steric
constraint. Thus, the reaction would lead to syn-product 4.
The model CE1 should be responsible for selective forma-
tion of anti-isomers 3 from 1 because this is free from
nonbonded interactions between the incoming nucleophile
and either R1 or Si′O substituents whereas the remaining
(5) See the Supporting Information for details.
(6) The sterically less demanding nature of an alkyne unit should be
responsible for the Z-selective conjugated enyne formation; see ref 4.
(7) The difference for stereochemical outcomes between (E)- and (Z)-
substrates when TMSOTf was employed might be rationalized by assuming
that the TMSOTf leads to a stable ion-pair intermediate between allyl-
propargyl hybrid cation and TfO-.
(8) (a) Cieplak, A. S. J. Am. Chem. Soc. 1981, 103, 4540-4552. (b)
Houk, K. N.; Moses, S. R.; Wu, Y.-D.; Rondan, N. G.; Jager, V.; Schohe,
R.; Fronczek, F. R. J. Am. Chem. Soc. 1984, 106, 3880-3882. See also:
Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; Wiley Interscience: New York, 1994; pp 876-886.
(9) For discussion pertinent to this issue, see: (a) Yamamoto, Y.;
Chounan, Y.; Nishi, S.; Ibuka, T.; Kitahara, H. J. Am. Chem. Soc. 1992,
114, 7652-7660. (b) Kim. J. D.; Zee, O. P.; Jung, Y. H. J. Org. Chem.
2003, 68, 3721-3724.
(10) (a) Wu, T.-C.; Goekjian, P. G.; Kishi, Y. J. Org. Chem. 1987, 52,
4819-4823. (b) Houk, K. N.; Eksterowicz, J. E.; Wu, Y.-D.; Fuglesang,
C. D.; Mitchell, D. B. J. Am. Chem. Soc. 1993, 115, 4170-4177.
(11) Perst, H. Oxonium Ion in Organic Chemistry; Verlag Chemie:
Weinheim, 1971.
(12) One of reviewers suggested on the basis of the reviewer’s own DFT
calculations using the Gaussian program that the cyclic oxonium ion has
much lower energy than the open-chain Z carbocation but, contrary to our
structure, it is totally planar. Our own efforts for this issue are now being
made using the Gaussian 03 program.
Org. Lett., Vol. 6, No. 9, 2004
1371

Since every process involved in Scheme 4 may occur with
minimum structural change,13 no geometrical isomerization
from 2 to 1 could be allowed.14
Optically pure bicyclic carbon frameworks bearing a linear
conjugated dienone function such as 10 (44% yield together
with the separable â-epimer 14%) or 11 (59% together with
the separable â-epimer 15%) was directly obtained from
conjugated 1,5-dien-7-yne frameworks 3g or 3n15 through a
Pauson-Khand reaction (Scheme 5). Considering the ready
generation of the corresponding acetylide anion and its
addition to aldehydes, oxidation of the thus-obtained ynol
to the ynone, hydrogenation of the triple bond using the
Lindlar catalyst to the enone, and final addition of trimeth-
ylsilylacetylide anion to the enone followed by treatment of
the resulting ynol with chlorotrimethylsilane.
In conclusion, we have disclosed the novel BF3‚OEt2-
promoted diastereoselective allylations of chiral allyl-prop-
argyl hybrid cations generated from acyclic precursors
leading to highly functionalized carbon frameworks of
synthetic interest. For (E)-substrates, the Cieplak conforma-
tion with the gauche-OCCC arrangement10 should play an
important role in determining the stereochemical outcomes.
On the other hand, ionization assisted by the combination
of the Lewis acid and the neighboring TBDMSO-group
attached to the stereogenic center should be crucial for the
diastereofacial differentiation of the (Z)-substrates.
Scheme 5. Synthetic Applicationsa
Acknowledgment. Financial support by a Grant-in-Aid
for Scientific Research on Priority Areas from the Ministry
of Education, Science, Sports, and Culture, Japan, is grate-
fully appreciated.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data including stereochemical
proofs. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL049847G
(13) For the principle of least motion, see: (a) Hine, J. J. Org. Chem.
1966, 31, 1236-1246. (b) Tee, O. S. J. Am. Chem. Soc. 1969, 34, 7144-
7149. (c) Jochum, C.; Gasteiger, J.; Ugi, I. Angew. Chem, Int. Ed. Engl.
1980, 7, 495-574.
(14) When 1j or 2m was subjected to the reaction conditions without
allyltrimethylsilane, these substrates were recovered unchanged. However,
such substrates in which a TBDMS group of 1j or 2m was replaced with
a TMS group were subjected to the conditions as just mentioned above,
hydride shift from the stereogenic center to the neighboring sp2 carbon took
place to give â,γ-unsaturated ketones in a significant amount. These results
suggest, though are not necessarily direct evidence, that we cannot
completely ruled out the possibility of the 1,2-participation by the TBDMSO-
group even for (E)-substrates.
(15) This compound was prepared from ethyl (S)-lactate through a series
of reactions involving TBDMS protection, DIBALH reduction, Horner-
Emmons reaction, and appropriate transformations directed to 3 as shown
in Scheme 5.
(16) Optically pure R-amino acids, R-hydroxycarboxylic acids, or
glyceraldehyde were used for the preparation of 1 and 2: see the Supporting
Information.
a Conditions: (a) (1) Co2CO8/CH2Cl2, (2) CH3CN, 65 °C, 15 h;
(b) CBr4, PPh3, NEt3; (c) (1) BuLi, (2) R2CHO, (3) SO3‚Py, NEt3;
(d) H2, Lindlar; (e) (1) TMSCC, BuLi, (2) TMSCl, imidazole.
availability of 1 from commercially available chiral carbon
sources,16 the present work may significantly serve organic
synthesis. For instance, starting from optically pure aldehyde
12, derived from the corresponding L-amino acid (R1 ) i-Pr/
L-valine),17 1h was prepared via an intermediate such as 13.
For preparation of the corresponding (Z)-isomer, the common
intermediate 12 was convenient and led to 2 (Scheme 5,
bottom)5 through a series of routine transformations involving
Corey’s procedure for formyl to ethynyl conversion,18 the
(17) A series of routine transformations from R-amino acids involving
deamination, esterification, O-protection, and reduction led to 1l.
(18) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769-3772.
1372
Org. Lett., Vol. 6, No. 9, 2004