Highly efficient ring closure of aromatic dialdehydes to macrocyclic allenes

Article abstract of DOI:10.1021/ja962868o

The one-pot double deoxygenation of simple alkyl- and polyether-tethered aromatic dialdehydes to give macrocyclic allenes has been accomplished in extraordinarily high yield without the need for slow-addition techniques, using a Ti(IV)-substituted ylide reagent and bis(trimethylsilyl)amide bases. Diastereoselective allene formation occurs when a binaphthyl unit is present in the substrate backbone, and the resulting cyclic allene is characterized by X-ray diffraction. Highly efficient cyclization is proposed to be the result of a combination of preorganization about the amide base counterion and a low concentration of the immediate precursor to Wittig-style olefination ring closure.

Full text of DOI:10.1021/ja962868o

VOLUME 119, NUMBER 15
APRIL 16, 1997
© Copyright 1997 by the
American Chemical Society
Highly Efficient Ring Closure of Aromatic Dialdehydes to
Macrocyclic Allenes
Marcus S. Brody, Robin M. Williams, and M. G. Finn*
Contribution from the Department of Chemistry, UniVersity of Virginia,
CharlottesVille, Virginia 22901
ReceiVed August 15, 1996X
Abstract: The one-pot double deoxygenation of simple alkyl- and polyether-tethered aromatic dialdehydes to give
macrocyclic allenes has been accomplished in extraordinarily high yield without the need for slow-addition techniques,
using a Ti(IV)-substituted ylide reagent and bis(trimethylsilyl)amide bases. Diastereoselective allene formation occurs
when a binaphthyl unit is present in the substrate backbone, and the resulting cyclic allene is characterized by X-ray
diffraction. Highly efficient cyclization is proposed to be the result of a combination of preorganization about the
amide base counterion and a low concentration of the immediate precursor to Wittig-style olefination ring closure.
We have recently developed a family of Ti(IV)-substituted
phosphorus methylides as “doubly oxophilic” reagents for the
convenient condensation of nonenolizable aldehydes to 1,3-
disubstituted allenes.1-4 An obvious extension of this meth-
odology is the synthesis of cyclic compounds from dicarbonyl
precursors (Scheme 1). Here we report several remarkably
efficient examples of such a process, along with a preliminary
exploration of the reaction scope and a discussion of its
important mechanistic features. Of particular interest are the
diastereoselective synthesis of a binaphthyl-tethered allene and
the preparation of several polyoxygenated macrocyclic allenes.
Scheme 1
vinylogous carbon-carbon,15-17 and polyether18,19 bonds, in-
variably in dilute solution. The conversion of dicarbonyl
compounds to large-ring cyclic olefins (defined here as having
ring sizes >10) has received somewhat less attention, most
(9) McQuillin, F. J.; Baird, M. S. Alicyclic Chemistry, 2nd ed.; Cambridge
University Press: Cambridge, 1983.
The most widely-used approaches to the closure of large
rings5-9 include the construction of ester,10-12 amide,13,14
(10) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull.
Chem. Soc. Jpn. 1979, 52, 1989-1994.
X Abstract published in AdVance ACS Abstracts, March 15, 1997.
(1) Hughes, K. A.; Dopico, P. G.; Sabat, M.; Finn, M. G. Angew. Chem.
Int., Ed. Engl. 1993, 32, 554-555.
(2) Reynolds, K. A.; Dopico, P. G.; Sundermann, M. J.; Hughes, K. A.;
Finn, M. G. J. Org. Chem. 1993, 58, 1298-1299.
(3) Reynolds, K. A.; Dopico, P. G.; Brody, M. S.; Finn, M. G. J. Org.
Chem. In press.
(11) Lee, J. Y.; Kim, B. H. Tetrahedron 1996, 52, 571-588.
(12) Sharma, A.; Sankaranarayanan, S.; Chattopadhyay, S. J. Org. Chem.
1996, 61, 1814-1816.
(13) Rodgers, S. J.; Ng, C. Y.; Raymond, K. N. J. Am. Chem. Soc. 1985,
107, 4095-4096.
(14) Schwartz, E.; Gottlieb, H. E.; Frolow, F.; Shanzer, A. J. Org. Chem.
1985, 50, 5469-5476.
(4) Reynolds, K. A.; Finn, M. G. J. Org. Chem. In press.
(5) Stille, J. K.; Tanaka, M. J. Am. Chem. Soc. 1987, 109, 3785-3786.
(6) Fujita, E. Pure Appl. Chem. 1981, 53, 1141-1154.
(7) Nicolaou, K. C. Tetrahedron 1977, 33, 683-710.
(8) Meng, Q.; Hesse, M. Topics in Current Chemistry: Ring Closure
Methods in the Synthesis of Natural Products; Springer-Verlag: Berlin,
1991.
(15) Ma, S.; Negishi, E. J. Am. Chem. Soc. 1995, 117, 6345-6357.
(16) Stille, J. K.; Su, H.; Hill, D. H.; Schnieder, P.; Tanaka, M.; Morrison,
D. L.; Hegedus, L. S. Organometallics 1991, 10, 1993-2000.
(17) Johnson, E. P.; Chen, G.-P.; Fales, K. R.; Lenk, B. E.; Szendroi, R.
J.; Wang, X.-J.; Carlson, J. A. J. Org. Chem. 1995, 60, 6595-6598.
(18) Patterson, I.; Mansuri, M. M. Tetrahedron 1985, 41, 3569-3624.
(19) Karin, M. R.; Sampson, P. J. Org. Chem. 1990, 55, 598-605.
S0002-7863(96)02868-5 CCC: $14.00 © 1997 American Chemical Society

3430 J. Am. Chem. Soc., Vol. 119, No. 15, 1997
Brody et al.
Scheme 2
Scheme 3
Table 1. Isolated Yields (with respect to ylide) of Macrocyclic
Allenes 2 from Dialdehydes 1
benefit can be derived from slow addition of the dialdehyde.29
Fortunately, yields improve dramatically upon dilution of the
reaction mixture from 5.0 mM in ylide to 1.4 mM, especially
for intermediate chain lengths (Table 1).
% yield vs ylide concentration
n
allene
ring size
5.0 mM
1.41 mM
2
4
5
6
8
3a
3b
3c
3d
3e
3f
11
13
14
15
17
19
25
32
34
34
44
27
45
80
85
90
(2) A standard procedure based on the intermolecular varia-
tion of the process1 was employed for reactions summarized in
Table 1, involving the addition of 4 molar equiv of the
dialdehyde to the phosphorus ylide solution. The excess
dialdehyde is easily recovered from the reaction mixture by
column chromatography. Alternatively, 2 equiv of a mono-
aldehyde may be introduced initially, followed immediately by
1.5 molar equiv of the desired dialdehyde substrate (all relative
concentrations are noted with respect to starting methylide;
Scheme 3). The only allenes observed in such cases derive
from the dialdehyde precursors, consistent with similar observa-
tions made for intermolecular condensation reactions.1,3 The
origin of this selective incorporation of the third and fourth
aldehyde equivalents introduced into the reaction mixture has
been described in detail elsewhere.30 Yields of cyclic allenes
obtained by this alternative procedure are generally 10-20%
lower with respect to ylide than for reactions shown in Table
1,31 but are obviously more efficient with respect to dialdehyde
if unreacted starting material is not recovered.
(3) In general, macrocyclic allenes are the only organic
products observed; no dimeric or oligomeric compounds are
detected even from reactions done at 5 mM ylide. The presence
of substantial quantities of vinylphosphonium salts, produced
as stable intermediates (see below), is ruled out by treatment
of the aqueous phase obtained from workup of the reaction
mixtures with NaBPh4, which we have found in other studies
to be an effective precipitating agent for alkyl- and vinylphos-
phonium salts of this kind. No such compounds were obtained.
The ring closure reaction proved to be much more sensitive
to the aromatic substitution pattern than to the length of the
alkyl tether. In contrast to substrates 2, meta-substituted
dialdehydes 4a-d under identical conditions afforded little
(<10%) allene at 5 mM ylide and no allene at 1.41 mM,
demonstrating that the conformational bias toward cyclization
provided by an ortho aromatic substitution pattern is required
for high yields. Surprisingly, allenes derived from inter-
molecular aldehyde coupling were not detected, even at fairly
high concentrations, and macrocyclic allene yields were not
increased for substrates 4 at reduced concentration. Therefore,
it appears likely that decomposition of a reaction intermediate
occurs in preference to dialdehyde cross coupling. An exception
87,a 87,b 40,c 70d
20,a 40,b 0c
10
a Using NaN(SiMe3)2. b Using KN(SiMe3)2. c Using KN(SiMe3)2 and
18-crown-6. d Using NaN(SiMe3)2 and 18-crown-6.
attempts involving reductive coupling, but some Wittig chem-
istry has been employed.20-23 The yields for these reactions
may be quite good (40-70% for 13- to 15-membered rings),
but the use of both high dilution (ca. 1 mM) and slow addition
techniques is required.
The double olefination methodology used here is a variation
of the simple, “one-pot” allene condensation procedure first
reported.1 Later work4 has identified the active reagent as a
combination of the titanium-substituted ylide species (Me2N)3-
PdC(H)TiCl(OiPr)2 (1) and the hindered base NaN(SiMe3)2.
The reactions are performed at room temperature under an inert
atmosphere without concern for slow addition. Thus, macro-
cyclic allenes are obtained in one step from convenient starting
materials, avoiding the multistep procedures that characterize
most allene syntheses.24-28
Results and Discussion
To explore the conformational and entropic requirements of
the ring-closure process, the alkyl-tethered ortho-salicylaldehyde
derivatives 2 were prepared by standard methods. As shown
in Scheme 2, treatment of a dilute solution of freshly-prepared
Ti-substituted ylide 1 and NaN(SiMe3)2 in THF with a solution
of each dialdehyde, followed by extractive workup and column
chromatography, provides macrocyclic allenes 3 in yields shown
in Table 1. The yields are remarkably high for 13- to
17-membered-ring sizes, especially since the n-alkyl tether is
highly flexible. Yields are lower for the 11-membered- and
19-membered-ring allenes, presumably due to torsional strain
in the former product and entropic barriers to cyclization in the
latter case.
Several important aspects of the process are noted below.
(1) Since the titanated ylide has been found to decompose
within 1 h at room temperature to methylphosphonium salt, no
(29) It does not prove to be advantageous to drop the temperature of
one-pot double olefination reactions.3 We have proposed that this is due to
an unfortunate decrease in the rate of an important deprotonation process
that must be fast in order to effectively compete with a decomposition
pathway.4
(30) Briefly, this effect arises from the complexation of aromatic
aldehydes by the two excess equivalents of NaN(SiMe3)2 present in the
titanated ylide mixture. The resulting R-amino alkoxide adducts provide
necessary basicity but remove those aldehyde equivalents from the
olefination process. See ref 3 for a complete discussion.
(20) McMurry, J. E. Acc. Chem. Res. 1983, 16, 405-411.
(21) Becker, K. B. Tetrahedron 1980, 36, 1717-1745.
(22) Nicolaou, K. C.; Seitz, S. P.; Pavia, M. R.; Petasis, N. A. J. Org.
Chem. 1979, 44, 4011-4013.
(23) Vollhardt, K. P. C. Synthesis 1975, 0, 765-780.
(24) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; John
Wiley & Sons: New York, 1984.
(25) Patai, S., Ed. The Chemistry of Ketenes, Allenes, and Related
Compounds, Parts 1 and 2; Wiley-Interscience: Chichester, 1980.
(26) Pasto, D. J. Tetrahedron 1984, 40, 2805-2827.
(27) Marshall, J. A.; Wang, X. J. Org. Chem. 1992, 57, 3387-3396.
(28) Okamura, W. H.; Aurrecoechea, J. M.; Gibbs, R. A.; Norman, A.
W. J. Org. Chem. 1989, 54, 4072-4083.
(31) For example, allene 3d is isolated in 75-85% yield if 2 equiv of
3,4,5-trimethoxybenzaldehyde are added to the Ti-substituted ylide mixture
(1.41 mM), followed by 1.5 equiv of dialdehyde 2d. Allene 3c is obtained
in 78% yield, 3e in 65% yield, and 9 in 49% yield (at room temperature)
by this method. The choice of “blocking” monoaldehyde may be made to
facilitate chromatographic separation.

Formation of Macrocyclic Allenes
J. Am. Chem. Soc., Vol. 119, No. 15, 1997 3431
Scheme 4
is dialdehyde 4a (n ) 3), which gave a 33% yield of the cyclized
alkyne 5, instead of the expected allene. It is possible that the
alkyne arises from an intermediate allene by base-induced
isomerization, driven by a release of ring strain. This may be
compared to the case of the corresponding ortho-substituted
dialdehyde 3a (n ) 2), which was converted to the cyclic allene
with no indication of the alkyne isomer.
Scheme 5
A possible explanation for the high yields of cyclic allenes
from dialdehydes 2 and the absence of dimeric or oligomeric
byproducts is a preorganization of the substrate or intermediate
about the Lewis acidic cation of the bis(trimethylsilyl)amide
base. A similar type of template effect has been described in
macrolactonizations14 and is a mainstay of crown ether synthesis.
In that event, the reaction outcome should depend upon the
identity of the cation. Indeed, when the cyclization of dialde-
hyde 2f is conducted in the presence of KN(SiMe3)2 instead of
the usual NaN(SiMe3)2, the yield of allene 3f increases from
20% to 40% (Table 1). In contrast, standard intermolecular
allene condensations are either unaffected or less efficient when
KN(SiMe3)2 is employed.1,3 Furthermore, no cyclic allene is
formed from 2f if KN(SiMe3)2 is used in the presence of an
equimolar amount of the potassium-selective complexing agent
18-crown-6. A similar effect is observed for the better substrate
2e, which is converted to allene in 87% yield using either NaN-
(SiMe3)2 or KN(SiMe3)2, 70% yield when the crown ether is
added to the sodium-containing reaction, but only 40% when
the crown ether is used in the presence of KN(SiMe3)2.
The reaction scope also extends to polyether-tethered dial-
dehydes 6a,b, which give cyclic polyethers 7a,b of comparable
ring size to the hydrocarbons 3 (Scheme 4). An upper limit to
the tether length was reached with 6c, which could not be
converted to the corresponding 23-membered cyclic allene. The
allenes 7a and 7b do not function as crown ethers toward
potassium ion when tested in a standard extractive assay.32
Figure 1. ORTEP drawing of the solid state structure of 9 showing
30% probability ellipsoids with atom numbering scheme. H atoms are
omitted for clarity. Pertinent dihedral angles: C2-C1-C39-C38
9.2(7)°, C2-C3-C4-C9 -15.5(8)°; C12-C13-C22n-C31 -96.6(5)°;
C39-C1-C3-C4 91.6°.
Lastly, the influence of a chiral moiety in the tether unit was
tested by examining the ring closure of binaphthyl dialdehyde
8, which afforded allene 9 in 79% yield at room temperature
(Scheme 5). A diastereomer ratio of 5:1 was measured by both
integration of the 1H NMR peaks of the allenic C-H units [6.35
(minor) and 6.05 ppm (major)] and the 13C NMR signals of the
central allene carbons [211.2 (minor) and 210.5 ppm (major)].
When the condensation reaction is performed at 0 °C, the
diastereomeric ratio is improved to 10:1, although total yield is
diminished (35%). A small amount of the pure major dia-
stereomer as a THF solvate was isolated by repeated column
chromatography of 9, prepared from enantiomerically pure (+)-
(R)-8, followed by recrystallization from THF/heptane. The
optical rotation of this compound was found to be [R]2D3 +411°
(c ) 0.180, dry THF), and its absolute configuration was
established by X-ray crystallography as the (R)-binaphthyl-(S)-
allene structure, as shown in Figure 1 and Table 2. This is
consistent with the observed optical rotation, assuming that the
large value characteristic of 1,3-diarylallenes ([R]2D5 g +459°
Table 2
empirical formula
formula weight
crystal color and habit
crystal system
C43H38O5
634.77
colorless block
monoclinic
a ) 8.572(2) Å
b ) 13.050(4) Å
c ) 14.752(5) Å
â ) 93.94(2)°
V ) 1646(2) Å3
P21 (No. 4)
2
lattice parameters
space group
Z
residuals R; Rw
goodness of fit
0.048; 0.061
1.64
for 1,3-diphenylallene)33 overcomes the chiroptical contribution
of the binaphthyl unit, and that the absolute configuration
correlation of a (+)-rotation with the (S)-allene enantiomer,
(33) Walbrick, J. M.; Wilson, J. W., Jr.; Jones, W. M. J. Am. Chem.
Soc. 1968, 90, 2895-2901. In this paper, the optical rotation of 1,3-
diphenylallene prepared from an enantiomerically pure cyclopropane
precursor is reported as [R]2D5 +459° in hexane. Recrystallization is
reported to give a compound with [R]2D5 +1020°, measured in ethanol. It is
(32) Koenig, K. E.; Lein, G. M.; Stuckler, P.; Kaneda, T.; Cram, D. J.
J. Am. Chem. Soc. 1979, 101, 3553-3566.

3432 J. Am. Chem. Soc., Vol. 119, No. 15, 1997
Brody et al.
Figure 2. Stereoscopic ORTEP drawing of the solid state structure of 9.
Scheme 6
derivatives of simple benzaldehydes that we have previously
examined,4 is unstable toward decomposition at room temper-
ature and is a competent Wittig reagent. Intramolecular
condensation with the pendant aldehyde group affords the cyclic
product (Scheme 6). The success of the cyclization process
results from the fortunate matching of the rates of two important
steps: the starting Ti-substituted ylide is rapidly consumed in
the selective formation of mono-vinylphosphonium salt 10, and
then 10 is deprotonated slowly by the hindered amide base.
Under these conditions, the steady-state concentration of allenic
phosphorane 11 is low, thus maximizing the chances for
intramolecular allene formation relative to intermolecular
condensation. In effect, the reaction mechanism manages its
own “slow addition” of phosphorus ylide to intramolecular
aldehyde in dilute solution.
reported for 1,3-diphenylallene and supported by theoretical
studies,34,35 is valid with respect to compound 9.
A stereo representation of the solid-state structure of (+)-9
is shown in Figure 2. The allene unit appears to be unstrained,
with each ortho-substituted aromatic group aligned substantially
in the sp2-plane of its adjacent allenic carbon. This allows for
overlap of the allene and aromatic π-orbitals, as is usual for
these systems and expected on the basis of the optical rotation
data. A cleft is formed between one naphthyl ring and the
allene, which are parallel to one another, although these units
do not appear to undergo a strong π-stacking interaction as
judged by the appearance of coincident 1H and 13C resonances
for the C1 and C3 positions in the NMR spectra. (The closest
contact is between the hydrogen on C1 and C30, 2.63 Å.) The
induction of S-allene stereochemistry by an R-binaphthyl tether
supports the prediction made on the basis of the calculated
energy differences between the two diastereomers. Molecular
mechanics analysis36 shows that the R-binol/S-allene diastere-
omer is approximately 2.0 kcal/mol lower in energy than the
R-binol/R-allene diastereomer.
Experimental Section
General Methods. THF and hexane were purified by distillation
from Na benzophenone ketyl. Ti(OiPr)4 was vacuum distilled and
stored under nitrogen. All other reagents were purchased from
commerical suppliers and used as recieved. NaN(SiMe3)2 was obtained
either as a solid or in THF solution from Lancaster Chemical Co. or
Aldrich Chemical Co. (Me2N)3PdCH2 was prepared as previously
described3 from P(NMe2)3 and CH3I; when desired, 13CH3I is used to
provide a label at the central allene carbon. TiCl2(OiPr)2 was prepared
by mixing equimolar hexane solutions of TiCl4 and Ti(OiPr)4. Di-
aldehydes were prepared by reaction of the appropriate R,ω-dibromide
with 10 equiv of the appropriate salicylaldehyde and K2CO3 in DMF
and purified by column chromatography; characterization data are
reported as Supporting Information. All manipulations involving ylide
species were conducted under dry nitrogen atmosphere. Reported yields
are the average of at least two independent runs, with an observed
variation of (5%. The cyclic allenes reported here are unstable upon
standing at room temperature in ambient light for more than 12 h but
may be stored for long periods in frozen benzene solution. In spite of
repeated attempts, we were unable to obtain satisfactory elemental
analyses for most of the reported allenes, which by NMR spectroscopy
appear to be pure. High-resolution mass spectrometry (HRMS) was
performed at the Department of Chemistry and Biochemistry, University
of Texas at Austin.
In conjunction with the results of a study of the intermolecular
allene-forming process, the reaction mechanism is proposed to
involve the conversion of dialdehyde to vinylphosphonium salt
10, followed by deprotonation by excess base (Scheme 6). The
resulting allenic phosphorane unit of 11, if analogous to
General Procedure for Cyclic Allene Synthesis. One equivalent
of (Me2N)3PdCH2 is added to 1.4 equiv of TiCl2(OiPr)2 in 10 mL of
THF. The resulting yellow-orange solution is treated immediately with
3 equiv of a THF solution of NaN(SiMe3)2, producing an immediate
color change to red-brown. THF is added to adjust the ylide
concentration to the desired value, followed immediately by the rapid
addition with stirring of the dialdehyde in 1 mL of THF solution. The
reaction mixture is allowed to stir at room temperature for 7-10 h,
and then the solvent is removed by rotary evaporation. The residue is
dissolved in CH2Cl2, filtered through a pad of Celite to remove insoluble
titanium byproducts, and purified by column chromatography (silica
gel, 7:1 light petroleum ether:CH2Cl2). After isolation of the allene,
not clear if the increase in optical rotation is due to an enrichment in
enantiomeric purity or to the change in solvent. Later theoretical papers34,35
show a match between calculations of optical rotation of 1,3-diphenylallene
and the lower of these two experimental values.
(34) Ruch, E.; Runge, W.; Kresze, G. Angew. Chem., Int. Ed. Engl. 1973,
12, 20-25.
(35) Runge, W.; Kresze, G. J. Am. Chem. Soc. 1977, 99, 5597-5603.
(36) Geometry minimization was performed using the MM2 force field
as implemented in Macromodel versions 4.0 and 4.5. Bond rotation about
the binaphthyl C-C single bond was not constrained in the calculation,
and so both diastereomers (composed of a single allene “epimer” and both
possible binaphthyl structures) were evaluated in a single Monte Carlo
conformational search of 15 000 starting structures, generating ten or more
duplicates of the minimum-energy conformation of each diastereomer.

Formation of Macrocyclic Allenes
J. Am. Chem. Soc., Vol. 119, No. 15, 1997 3433
which usually comprises the least polar material in the mixture, excess
aldehyde may be recovered by elution with higher concentrations of
CH2Cl2.
6.5 (d, J ) 8.1 Hz, 2H), 6.1 (s, 2H), 4.1 (m, 4H), 3.9 (m, 4H); 13C
NMR (CDCl3) δ 210.7, 155.8, 154.0, 134.1, 129.4, 128.6, 127.6, 127.3,
126.1, 125.0, 123.5, 123.4, 121.2, 120.4, 116.1, 111.3, 90.5, 68.0, 67.2;
UV-vis (MeOH) 204, 228; UV-vis (CH2Cl2) 206 (ꢀ ) 7.3 × 104),
230 (ꢀ ) 9.9 × 104), 262 (shoulder, ꢀ ) 2.2 × 104), 294 (shoulder, ꢀ
) 1.3 × 104), 334 (shoulder, ꢀ ) 3.8 × 103); HRMS: calcd for
C39H30O4 562.2142, obsd 562.2128. Optical rotation was measured
on the same sample of the pure major diastereomer used for crystal-
lographic analysis, [R]23D +411° (c ) 0.180, dry THF), and for a 2.35:1
3a: 1H NMR (CDCl3) δ 7.2 (m, 4H), 7.1 (m, 4H), 6.3 (s, 2H), 4.3
(d, J ) 9.2 Hz, 2H), 4.0 (d, J ) 9.2 Hz, 2H); 13C NMR (CDCl3) δ
212.8, 157.6, 129.9, 128.0, 127.6, 123.9, 121.0, 89.4, 73.6; IR (CH2-
Cl2) 1932; UV-vis (CH2Cl2, nm) 225, 260 cm-1; mp 142-144 °C.
Anal. Calcd for C17H14O2: C, 81.58; H, 5.64. Found: C, 81.78; H,
6.00.
3b: 1H NMR (CDCl3) δ 7.7 (m, 4H), 6.9 (m, 4H), 6.5 (s, 2H), 4.1
(t, 4H), 1.4 (m, 4H); 13C NMR (CDCl3) δ 211.2, 156.3, 139.1, 127.7,
125.3, 121.3 115.0, 91.3, 70.4, 26.3; IR (CDCl3) 1934 cm-1; UV-vis
(CH2Cl2) 225, 260 nm; mp 148-149 °C (sample recrystallized from
CH2Cl2/EtOH); HRMS (chemical ionization): calcd for [M + 1]
C19H19O2, 279.1384, obsd 279.1385.
ratio of diastereomers, [R]23 +206° (c ) 12.9, THF). The minor
D
diastereomer shows an analogous set of 1H NMR peaks, with the
greatest differences being the appearance of the allenic C-H at 6.3
ppm (vs 6.1 ppm), and a doublet at 6.7 (J ) 8.1 Hz, 2H; vs 6.5 ppm).37
X-ray Crystallography. X-ray measurements were carried out on
a Rigaku AFC6S diffractometer using Mo KR radiation (λ ) 0.71069
Å). Calculations were performed on a VAXstation 3500 computer
using the TEXSAN 5.0 software38 and in the later stages on a Silicon
Graphics Personal Iris 4D35 computer with the teXsan 1.7 package.39
Relevant crystallographic data are listed in Table 2. Unit cell
dimensions were determined by applying the setting angles of 25 high-
angle reflections. Three standard reflections were monitored during
the data collection showing no significant variance. The structure was
solved by direct methods in SIR88.40 Full-matrix least-squares refine-
ment with anisotropic displacement parameters for all non-hydrogen
atoms yielded the final R of 0.048 (Rw ) 0.061). All hydrogen atoms
were found in difference Fourier maps and included in calculations
without further refinement. The final difference map was essentially
featureless with the highest peak of 0.2 e/A3. The results of the
refinement are presented in Table 2.
3c: 1H NMR (CDCl3) δ 7.24 (d, J ) 7.7 Hz, 2H), 7.1 (t, J ) 6.2
Hz, 2H), 6.9 (m, 4H), 6.6 (s, 2H), 4.2 (m, 2H), 3.9 (m, 2H), 1.8 (m,
2H), 1.7 (m, 2H), 1.6 (m, 2H); 13C NMR (CDCl3) δ 210.1, 157.0, 129.4,
127.9, 124.2, 120.9, 113.5, 91.2, 68.9, 28.5, 22.3; IR (CH2Cl2) 1945
cm-1; UV-vis (CH2Cl2) 225, 260, 295 nm; mp 136-138 °C (sample
recrystallized from CH2Cl2/EtOH); HRMS (chemical ionization): calcd
for [M + 1] C20H21O2 293.1540, obsd 293.1536.
3d: 1H NMR (CDCl3) δ 7.3 (m, 6H), 6.9 (m, 2H), 6.6 (2, 2H), 4.1
(m, 4H), 1.8 (m, 4H), 1.5 (m, 4H); 13C NMR (CDCl3) δ 209.4, 129.3,
127.5, 125.2, 120.7, 113.1, 90.4, 63.5, 29.2, 27.2, 21.9; IR (CDCl3)
2921, 2867, 1942 cm-1; UV-vis (CH2Cl2) 225, 260 nm; mp 111-112
°C (sample recrystallized from CH2Cl2/EtOH); HRMS (chemical
ionization): calcd for [M + 1] C21H23O2 307.1697, obsd 307.1697.
3e: 1H NMR (CDCl3) δ 7.1 (m, 8H), 6.7 (s, 2H), 4.1 (t, J ) 11.4
Hz, 4H), 1.5 (m, 12H); 13C NMR (CDCl3) δ 210.3, 155.8, 128.9, 127.6,
122.9, 120.2, 111.6, 91.1, 68.2, 29.0 28.9, 25.8; IR (CDCl3) 1943 cm-1
;
Acknowledgment is made to the donors of the Petroleum
Research Fund, administered by the American Chemical Society,
for partial support of this research (27397-AC1). Support from
the National Science Foundation (CHE 93-13746) and Cam-
bridge Isotope Laboratories (for a generous grant of 13CH3I
through the CIL Research Grant Program) is gratefully ac-
knowledged. We thank Dr. Michal Sabat for X-ray crystal-
lography of allene 9.
UV-vis (CH2Cl2) 225, 260, 310 nm; isolated as an oil; HRMS: calcd
for C23H26O2 334.1931, obsd 334.1916.
3f: 1H NMR (CDCl3) δ 7.1 (m, 8H), 6.7 (s, 2H) 4.0 (m, 4H); 1.1
(m, 16H); 13C NMR (CDCl3) δ 211.4, 156.7, 129.6, 128.2, 123.4, 120.6,
114.6, 111.5, 91.6, 67.5, 29.2, 27.5, 26.6, 25.6; IR (CDCl3) 1960 cm-1
;
UV-vis (CH2Cl2) 225, 260, 310 nm; mp 84-85 °C (sample recrystal-
lized from CH2Cl2/EtOH); HRMS (chemical ionization): calcd for [M
+ 1] C25H31O2 363.2322, obsd 363.2310.
5: 1H NMR (CDCl3) δ 7.3 (m, 6H), 7.01 (m, 2H), 4.5 (t, J ) 5.4
Hz, 2H), 4.4 (t, J ) 5.4 Hz, 2H), 3.8 (s, 2H), 2.3 (p, J ) 5.4 Hz, 2H);
13C NMR (CDCl3) δ 132.4, 130.4, 129.5, 128.4, 126.5, 123.4, 121.9,
121.4, 121.1, 120.2, 115.7, 95.3, 90.5, 70.6, 68.3, 65.0, 29.6, 23.9; IR
(CDCl3) 3053, 2879, 1936, 1599 cm-1. HRMS (chemical ionization):
calcd for [M] C18H16O2, 264.1150, obsd 264.1145.
Supporting Information Available: Characterization data
for dialdehydes 2, 6, and 8, and X-ray crystal structure data for
allene 9 (11 pages). See any current masthead page for ordering
and Internet access instructions.
JA962868O
7a: 1H NMR (CDCl3) δ 7.3 (dd, J ) 7.7, 1.5 Hz, 2H), 7.2 (dt, J )
8.1, 1.8 Hz, 2H), 6.9 (t, J ) 7.3 Hz, 2H), 6.8 (d, J ) 8.1 Hz, 2H), 6.8
(s, 2H), 3.8 (m, 12H), 1.2 (s, 4H); 13C NMR (CDCl3) δ 211.0, 158.0,
129.1, 127.7, 120.8, 112.1, 91.1, 71.2, 69.6, 68.1; IR (CDCl3) 1938
cm-1; UV-vis (CH2Cl2) 225, 260, 300 nm; HRMS (chemical ioniza-
tion): calcd for [M + 1] C21H23O4 339.1595, obsd 339.1596.
7b: 1H NMR (CDCl3) δ 7.4 (d, J ) 7.5 Hz, 2H), 7.2 (t, J ) 6.9 Hz,
2H), 6.9 (m, 4H), 6.8 (s, 2H), 4.3 (m, 4H), 4.1 (m, 4H), 3.8 (m, 4H),
3.7 (s, 4H); 13C NMR (CDCl3) δ 211.2, 156.5, 129.5, 128.2, 123.9,
121.3, 112.4, 91.7, 71.6, 71.1, 69.9, 68.7; IR (CDCl3) 1940 cm-1; UV-
vis (CH2Cl2) 225, 260, 300 nm; isolated as an oil; HRMS (chemical
ionization): calcd for [M + 1] C23H27O5 383.1856, obsd 383.1851.
For 9, the major diasteromer may be purified by column chroma-
tography or by recrystallization by diffusion of heptane into a THF
solution of the allene. Characterization data (major diastereomer): 1H
NMR (CDCl3) δ 7.9 (d, J ) 8.8 Hz, 2H), 7.8 (d, J ) 8.1 Hz, 2H), 7.4
(d, J ) 9.2 Hz, 2H), 7.2, (m, 3H), 7.7 (m, 3H), 6.8 (t, J ) 6.6 Hz, 2H),
(37) From the value obtained for the pure diastereomer, one would expect
an optical rotation of approximately 166° for a 2.35:1 diastereomeric
mixture, if the allene moiety was the sole contributor. A comparison with
the observed value shows that the contribution of the binaphthyl fragment
is of similar magnitude to the optical rotation of the binaphthyl dialdehyde
precursor 8, as expected. Circular dichroism (THF, 5.78 µM) of the pure
major diastereomer showed a negative Cotton effect, with extrema at 225
(∆ꢀ ) 18.9 mdeg) and 237 nm (∆ꢀ ) -22.8 mdeg), matching that of the
binaphthyl aldehyde 8. The CD spectra of diarylallenes have been shown
to strongly resemble those of binaphthyls in this frequency range [Mason,
S. F.; Vane, G. W. Tetrahedron Lett. 1965, 1593-1597]. In addition, a
region of negative ∆ꢀ extends from 250 to 266 nm (∆ꢀ ) ca. 5-8 mdeg)
that is not exhibited by compound 8.
(38) TEXSAN 5.0: Single Crystal Structure Analysis Software. Molec-
ular Structure Corp.: The Woodlands, TX 77381, 1989.
(39) teXsan 1.7: Single Crystal Sructure Analysis Software. Molecular
Structure Corp.: The Woodlands, TX 77381, 1995.
(40) Burla, M. C.; Camalli, M.; Cascarano, G.; Giacovazzo, C.; Polidori,
G.; Spagna, R.; Viterbo, D. J. Appl. Crystallogr. 1989, 22, 389.