First demonstration of helical chirality in 1,4-disubstituted (Z,Z)-1,3-dienes: R3Si-SnR'3-mediated cyclization of 1,6-diynes [11]

Full text of DOI:10.1021/ja0015500

J. Am. Chem. Soc. 2000, 122, 8579-8580
Scheme 1. Formation of a Chiral (Z,Z)-1,3-Diene from a
8579
First Demonstration of Helical Chirality in
1,4-Disubstituted (Z,Z)-1,3-Dienes:
Diyne
R3Si-SnR′3-Mediated Cyclization of 1,6-Diynes
Sandra Gre´au, Branko Radetich, and T. V. RajanBabu*
Department of Chemistry, 100 West 18th AVenue
The Ohio State UniVersity, Columbus, Ohio 43210
ReceiVed May 5, 2000
1,2-Bis-alkylidenecycloalkane derivatives prepared from R,ω-
diynes or eneynes are valuable intermediates in organic synthesis.1
Catalytic methods which convert diynes to functionalized bis-
alkylidene derivatives invariably use bifunctional reagents,
X-Y, which can undergo oxidative addition to low-valent
transition metals (Scheme 1). Thus, metal-catalyzed cyclization
of 1,6-diynes can be accomplished under hydrosilylation,2a-c
hydrostannylation,2d borosilylation,2e and borostannylation2f con-
ditions. However, an important stereochemical aspect of this
reaction, brought about as a necessary consequence of the organo-
metallic reaction mechanisms involved (Scheme 1), viz., the
formation of a (ZZ)-1,3-diene, has received little attention in the
literature. This work addresses this issue in the context of a highly
versatile bis-functionalization/cyclization of 1,6-diynes assisted
by trialkylsilyltrialkyltin reagents, a class of compounds known
to undergo Pd(0)-catalyzed addition to acetylenes with high regio-
and stereoselectivity.3 Sterically demanding silicon and tin
substituents impose a nonplanar, therefore, helically chiral
structure for such a diene. To the best of our knowledge, helical
chirality associated with terminally substituted (ZZ)-1,3-dienes
has not been disclosed in the literature, even though the first
member of this class of compounds has been known for some
time.2f
Scheme 2. Enantiomers of 2 at -40 °C
1H NMR (500 MHz, CDCl3) of 2 is characterized by the following
peaks: 0.05 (s, SiCH3, 9 H), 0.85-0.88 (t superimposed on m,
2
H2C-CH3, SnCH2, 15 H, JSn,H satellites), 1.24-1.29 (m, CH2,
6 H), 1.38-1.44 (m, CH2, 6 H), 2.66-3.20 (ring CH2, s, broad,
4 H), 3.69 (s, OCH3, 6 H), 5.23 (s, Me3SiCH, 1 H), 5.65 (s,
Bu3SnCH, 1 H, 1JSnH 50 Hz). Irradiation of the olefinic signals at
δ 5.23 and 5. 65 causes enhancements of the broad peak centered
around δ 2.93 (ring CH2) which support the (ZZ)-assignment of
the diene. The extraordinarily broad signals due to the ring
methylene hydrogens (at 20 °C: peak width ≈ 0.54 ppm) gave
the first indication of a possible fluxional molecule. Upon
warming to 50 °C, the peaks resolve into two broad singlets
centered around δ 2.97 and 3.01. When a CD2Cl2 solution is
cooled to -40 °C, two sets of signals appear as AB quartets
around δ 3.12 (νA ) 3.10, νB ) 3.14, JAB ) 9 Hz) and at δ 2.72
(νA ) 2.69, νB ) 2.75, JAB ) 14 Hz). Between 20 and -40 °C
the changes in the spectrum can be interpreted as arising from
two closely spaced AB systems, undergoing A-B exchange, with
a coalescence temperature between -10 and -5 °C. At -40 °C,
the CO2Me signals also resolve into two singlets at δ 3.748 and
3.756. The evolution of the two AB quartets for the ring CH2
group and the doubling of the carbon signals5 are possible only
if the molecule is chiral. Barring a highly unlikely conformational
equilibrium involving the cyclopentane, such chirality must have
its origin in the helical arrangement of groups in the (ZZ)-diene
(Scheme 2). Failure of the diene to undergo Diels-Alder reaction
with dienophiles including maleic anhydride (150 °C) also sup-
ports the unusual nonplanar arrangement of the 1,4-substituents.
Another derivative 2c, with larger Si-substituents exhibits similar
behavior including diastereotopic SiMe2 groups, except, as
expected, the coalescence temperatures for the diastereotopic
hydrogen and carbon signals are approximately 10-15 °C higher.4
Cyclizations of a number of other 1,6-diynes were carried
out and the results are shown in Table 1. Methyl 2-(2-propynyl)-
4-pentynoate 3 gave 66% isolated yield of a product (4) which
The structure, stereochemistry, and the fluxional nature of
the compound 2 prepared from di-O-methyl dipropargylmalonate
(eq 1) were unambiguously established by elemental analysis
(C, H) and NMR spectroscopy (1H, 13C, and 119Sn, COSY,
NOESY, DEPT and variable temperature experiments).4 The
(1) For recent reviews see: (a) Vollhardt, K. P. C. Angew. Chem., Int. Ed.
Engl. 1984, 23, 539. (b) Tamao, K.; Kobayashi, K.; Ito, Y. Synlett 1992, 539.
(c) Grotjahn, D. B. In ComprehensiVe Organometallic Chemistry II; Hegedus,
L. S., Ed.; Pergamon/Elsevier: Kidlington, 1995; p 741. (d) Negishi, E.-i.;
Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. ReV. 1996, 96, 365. (e) Ojima,
I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV. 1996, 96, 635. (f)
Trost, B. M. Angew. Chem., Int. Ed. Engl. 1992, 31, 305. (g) Sato, Y.;
Nishimata, T.; Mori, M. Heterocycles 1997, 44, 443. (h) Ogawa, R.; Itoh, K.
J. Org. Chem. 1998, 63, 9610 and references therein. (i) Nugent, W. A.; Thorn,
D. L.; Harlow, R. L. J. Am. Chem. Soc. 1987, 109, 2788.
(2) (a) Tamao, K.; Kobayashi, K.; Ito, Y. J. Am. Chem. Soc. 1989, 111,
6478. (b) Muraoka, T.; Matsuda, I.; Itoh, K. Tetrahedron Lett. 1998, 39, 7325.
(c) For a recent related reports of hydrosilylation/carbonylation, see: Chatani,
N.; Fukumoto, Y.; Ida, T.; Murai, S. J. Am. Chem. Soc. 1993, 115, 11614;
Ojima, I.; Lee, S.-Y. J. Am. Chem. Soc. 2000, 122, 2385 and references therein.
(d) Lautens, M.; Smith, N. D.; Ostrovsky, D. J. Org. Chem. 1997, 62, 8970.
(e) Onozawa, S.; Hatanaka, Y.; Tanaka, M. J. Chem. Soc., Chem. Commun.
1997, 1229. (f) Onozawa, S.; Hatanaka, Y.; Choi, N.; Tanaka, M. Organo-
metallics 1997, 16, 5389.
(5) The 13C spectrum4 is characterized by the signals at δ 0.43 (q, SiCH3),
1
10.71 (t, SnCH2, JSn,C ) 336 Hz), 13.64 (q, SnCH2CH2CH2CH3), 27.32
2
3
(t, SnCH2CH2, JSn,C ) 59 Hz), 28.95 (t, SnCH2CH2CH2, JSn,C ) 20 Hz),
44.07 (t, CH2, 1 C), 44.10 (t, CH2, 1 C), 52.72 (q, OCH3, 2 C), 55.05 (s,
C(CO2Me)2, 1 C), 125.57 (d, HCSn, 1 C), 126.21 (d, HCSi, 1 C), 155.34 (s,
1 C), 155.89 (s, 1 C), 172.11 (s, CO). The 13C spectrum also shows the
doubling of the CO2CH3 and CO2CH3 carbons at -40 °C. The ring CH2
carbons are also better resolved at -40 °C.
(3) (a) Chenard, B. L.; Laganis, E. D.; Davidson, F.; RajanBabu, T. V. J.
Org. Chem. 1985, 50, 3666. (b) Mitchell, T. N.; Killing, H.; Dicke, R.;
Wickenkamp, R. J. Chem. Soc., Chem. Commun. 1985, 345.
(4) See Supporting Information for details, including VT NMR spectra and
a discussion of criteria of purity (NMR and HPLC) of key compounds.
10.1021/ja0015500 CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/19/2000

8580 J. Am. Chem. Soc., Vol. 122, No. 35, 2000
Scheme 3. Helical Chirality in 4 at Low Temperature
Communications to the Editor
Figure 1. X-ray structures of 10a and 10b (cations, H’s omitted for
clarity).
completely in agreement with the suggested equilibrium between
two sets of diastereomers at low temperature (Scheme 3). The
corresponding But(Me)2Si- derivative 4c provided the most
unequivocal evidence for the equilibration with doubling of the
largest number of signals in going from 20 °C to -40 °C. These
include, Si(CH3)2, ring CH2’s, CO2CH3 in the proton spectrum,
ring CH2’s, ring CH, carbonyl C, SnCH, SiCH in the 13C
spectrum, and the Sn signal in the 119Sn spectrum.4
Table 1. Silylstannylation-Cyclization of 1,6-Diynesa
The reaction conditions are compatible with amino and amido
groups, allowing access to functionalized heterocycles (8, 10,
entries 4, 5). In VT NMR and nOe experiments,4 8 behaves like
2, in which the equilibration process is slow below -40 °C,
resulting in one of the ring CH2 groups to appear as a true ABq
at low temperature. NMR spectra of 10, prepared from dipro-
pargylamine 9, are indicative of a single compound (fast N-
inversion and helical equilibration remove any potential diastereo-
isomerism) at room temperature. The low-temperature spectra
recorded in CD3OD are much less resolved compared to the
carbocyclic compounds, nonetheless, a mixture of diastereomers
is indicated at temperatures below -60 °C. Quaternization of 10
with methyl triflate removes the nitrogen inversion, and a set of
diastereomeric triflate salts, characterized by, inter alia, a pair of
SiCH and SnCH signals, are produced at room temperature.4
Finally, a crystalline oxalate salt of the pyrrolidine derivative
10 was found to contain, in its unit cell, two of the four possible
diastereomers, in which the diene helicity can be clearly seen.
Chem3D renditions of these structures with selected intra-
molecular distances and angles are shown in Figure 1.6 The
epimerization reaction, observed in the NMR spectra, is apparently
frozen in the solid state, permitting isolation of the individual
diastereomers.
a See Supporting Information for experimental procedures. b Using
(2-Me-C6H4)3P.
was readily separated on a chiral HPLC column (Chiracel OD,
25 cm × 4.6 mm, 100% hexane, flow rate of 0.1 mL/min. Rt )
37.50, 42.22 min.). As expected, 4 is a highly fluxional molecule.
The ring methylenes which appear as two broad doublets (CDCl3)
at δ 2.555 and 2.591 (each ∼J ) 8 Hz) at 27 °C resolves into
two ABX patterns at 65 °C (in C6D6).4 The low-temperature
spectrum is very complex, yet four sets of ABX patterns are
clearly discernible in the spectrum below -40 °C. The tem-
perature-dependent changes in the 13C spectrum of this com-
pound are indeed remarkable,4 and all of the changes are
Acknowledgment. We acknowledge the financial assistance by the
U.S. National Science Foundation (CHE-9706766). We thank Dr. Judith
C. Gallucci for the X-ray crystallographic analysis.
Supporting Information Available: Experimental procedures for the
synthesis of precursors and products listed in Table 1; VT NMR spectra
1
of compounds 2, 2c, 4, 4c, 6, 8, 10, [10-Me]+[OTf]- and H NMR of
10a/b (PDF). This material is available free of charge via the Internet at
http://pubs.acs.org.
JA0015500
(6) Because of disorders in the crystal, complete solution of the structure
was not possible, even though reliable data on the ammonium ion could be
extracted.