(GCMS) (in both EI and CI mode) exhibited molecular ions
at m/z 380 and 394, respectively, indicating the formulas
C27H56 and C28H58. These were confirmed by accurate mass
measurements (HRMS), i.e., 380.4373 (calcd for C27H56
380.4832) and 394.4549 (calcd for C28H58 394.4536).
The mass spectral fragmentation pattern of each compo-
nent demonstrated the presence of multiple methyl branches,
with a number of consecutive losses of 42 amu (or C3H6
units) consistent with an alternating methyl branching pattern
as exhibited by 1 and 2.
High-resolution 13C NMR and DEPT spectra (187 MHz)
confirmed the presence of five and six methyl branches in
the C27 and C28 hydrocarbons, respectively, with the
requisite number of methine and methylene signals consistent
with the proposed saturated hydrocarbons. The location of
methyl branches along the C22 carbon chain was based on
mass spectral and NMR interpretation and shift calculations.
On this basis, at least three methyls were located on alternate
carbons on a C5 carbon unit (Figure 1). 13C NMR shifts were
gland wax of the graylag goose.4 To explore the possibility
that hydrocarbons 2 and 3 may possess the all-syn stereo-
chemistry as well, we fully assigned the NMR spectra of
lardolure 4 (see Supporting Information). These and other
data for polymethylated alkanes5 strongly indicated that the
all-syn arrangement was not present in 2 or 3. However, the
16,18-dimethyl fragment in 2 was syn. This was established
by comparisons of the methyl 13C chemical shifts for syn
(unresolved at δ 20.3) and anti (unresolved at δ 19.6) 7,9-
dimethylhexadecane (acquired from cis- and trans-3,5-
dimethylcyclohexanol; see Supporting Information) with
those for the C16 and C18 methyl groups of the natural
compound, 2, at δC 20.3.
The foregoing analyses, when applied to the tetrad unit,
suggested that the most favored relative stereochemistries
for it were anti-syn-anti-5 or anti-anti-anti-6, with 7-12
being unlikely. The various possibilities are shown in Figure
2, with all structures indicating relative stereochemistry only.
Figure 1.
then calculated for a number of alternative structures, using
an equation derived from the Lindeman-Adams rule.2
For the C28 hydrocarbon, it was deduced that the first
methyl branch at each end was four carbons from one end
and five carbons from the other end. Structures 1 and 2 had
calculated 13C NMR shifts in best agreement with the
experimental data and differ only in the number of methyl-
enes at each end of the molecule. Two-dimensional NMR
experiments (COSY, HMBC, and HSQC) provided a clear
distinction in favor of 2.
The constitution of the C27 hydrocarbon was similarly
deduced to be 4,6,8,10,16-pentamethyldocosane 3, with the
calculated 13C NMR resonances being in very good agree-
ment with those observed. Mass spectral fragmentation data
are consistent with the structures 2 and 3 (see Supporting
Information).
Figure 2.
Syntheses of these unusual hydrocarbons were undertaken
to confirm constitutional and stereochemical features. The
general approach to isomers of 2 and 3 is illustrated by the
acquisition of a mixture of the anti-anti-anti system 6 and
the anti-anti-syn system 11. 2,4,6-Trimethylphenol 13 was
transformed to the alcohol 26 by the sequence summarized
in Scheme 1. Two one-carbon chain extensions by inverting
cyanide displacement of mesylate to form 19 and 22 are the
important elements. A similar undertaking, but now with cis-
3,5-dimethylcyclohexanol, afforded syn Wittig salt and then
the ylide 28.
Aldehyde 27 was generated as needed and immediately
coupled with the ylides 28 and 29 to afford the alkenes 30
and 31, respectively, which were reduced to the hydrocarbons
32 and 33, respectively, each as a mixture of four major
The 4,6,8,10-tetramethyl pattern present in 2 and 3 was
previously identified in lardolure 4,3 the aggregation phero-
mone of an acarid mite, and demonstrated to have syn, (R)-,
stereochemistry (4). This unit is also present in the preen
(4) Mori, K.; Kuwahara, S. Liebigs Ann. Chem. 1987, 555.
(5) (a) Asakura, T.; Omaki, K.; Zhu, S.-N.; Chujo, R. Polymer J. 1984,
16, 717. (b) Tonelli, A. E. Macromolecules 1978, 12, 83. (c) Provasoli, A.;
Ferro, D. R. Macromolecules 1977, 10, 874. (d) Tonelli, A. E.; Schilling,
F. C. Acc. Chem. Res. 1981, 14, 233.
(2) (a) Lindeman, L. P.; Adams, J. Q. Anal. Chem. 1973, 43, 1245. (b)
Wehrli, F. W.; Wirthlin, T. Interpretation of Carbon-13 NMR Spectra;
Heydon: London, 1976; p 41.
(3) Mori, K.; Kuwahara, S. Tetrahedron 1996, 42, 5545.
5084
Org. Lett., Vol. 5, No. 26, 2003