Bridging the final gap in stereocontrolled Wittig reactions: Methoxymethoxy-armed allylic phosphorus ylides affording conjugated dienes with high cis selectivity

Article abstract of DOI:10.1002/(SICI)1521-3765(20000204)6:3<420::AID-CHEM420>3.0.CO;2-H

After treatment with an appropriate base (butyllithium or sodium amide), 2-alkenyltris(2-methoxymethoxyphenyl)phosphonium salts carrying an allyl, crotyl, or prenyl (3-methyl-2-butenyl) side chain condense with saturated or unsaturated aldehydes to give conjugated dienes with Z/E ratios ranging from 90:10 to >99:1 and averaging 96:4. Owing to steric congestion, yields are only moderate (on average 41%; extremes 10-79%). The nonvolatile tris(2- methoxymethoxyphenyl)phosphine oxide by-product can be readily isolated and reduced to recover the phosphane starting material, or it may be hydrolyzed to the water-soluble tris(2-hydroxyphenyl)phosphine oxide.

Full text of DOI:10.1002/(SICI)1521-3765(20000204)6:3<420::AID-CHEM420>3.0.CO;2-H

FULL PAPER
Bridging the Final Gap in Stereocontrolled Wittig Reactions:
Methoxymethoxy-Armed Allylic Phosphorus Ylides Affording Conjugated
Dienes with High cis Selectivity
Qian Wang, Mirella El Khoury, and Manfred Schlosser*[a]
Abstract: After treatment with an appropriate base (butyllithium or sodium amide),
2-alkenyltris(2-methoxymethoxyphenyl)phosphonium salts carrying an allyl, crotyl,
or prenyl (3-methyl-2-butenyl) side chain condense with saturated or unsaturated
aldehydes to give conjugated dienes with Z/E ratios ranging from 90:10 to >99:1 and
averaging 96:4. Owing to steric congestion, yields are only moderate (on average
41%; extremes 10 ± 79%). The nonvolatile tris(2-methoxymethoxyphenyl)phos-
phine oxide by-product can be readily isolated and reduced to recover the phosphane
starting material, or it may be hydrolyzed to the water-soluble tris(2-hydroxyphen-
yl)phosphine oxide.
Keywords: alkenes
synthesis ´ 1,3-dienes ´ phosphorus
ylides ´ Wittig reactions
´
asymmetric
hexylphosphorane[12]) are employed. Ylides carrying strongly
electron-withdrawing heterofunctional substituents (in par-
ticular, acyl and alkoxycarbonyl groups) at the a-position of
the side chain are called ªstabilizedº since they resist hydro-
lytic and oxidative decomposition under ordinary conditions.
All of them favor more or less the formation of E olefins. The
corresponding PO ylides (ªHorner reagentsº), however, can
be structurally tuned to afford predominantly either Z or E
isomers. For example, when consecutively treated with a base
and an aldehyde, diethyl (or dimethyl) methoxycarbonyl-
methyl phosphonate[13, 14] and 1-(methoxycarbonyl)ethyl
phosphonate[8, 15, 16] produce Z/E ratios averaging 5:95, but
the corresponding di(2,2,2-trifluoroethyl)phosphonates give
mainly the Z isomers (Z/E 87:13 ± 98:2).[8, 17±23] Even diethyl
and dimethyl a-ester phosphonates become cis-selective when
they are allowed to react with a-alkoxyalkanals[21, 24±29] or a-
(N-sulfonylamino)alkanals[18] in polar protic solvents such as
methanol.[30] Diphenyl or diaryl ethoxycarbonylmethyl phos-
phonates or 1-(ethoxycarbonyl)ethyl phosphonate reveal an
intrinsic tendency to afford mainly the Z-configured enesters
(Z/E 78:22 ± 99:1) when condensed with saturated, a,b-
unsaturated, and aromatic aldehydes.[31, 32] Conversely, diiso-
propyl phosphonates carrying an a-ester side chain provide
particularly elevated E selectivities.[33±36]
Introduction
This report concludes our long efforts to introduce stereo-
selectivity into the Wittig procedure. At the beginning of our
systematic investigations, some 35 years ago, we were lucky
enough to discover ways to control the outcome of the
reaction between a phosphorus ylide having an alkyl side
chain (a so-called reactive ylide) and an aldehyde, thus making
either one of the two possible stereoisomers optionally
accessible. The cis selectivity achieved in media free of
lithium salts initially averaged Z/E ratios of only 95:5,[1±3] but
was later improved to reach the 99:1 level in many cases.[4] The
trans-selective olefination,[2, 3, 5] relying on betaine ylides as
readily epimerizing intermediates, met the mark of Z/E < 1:99
from the outset.
Prior to our work, a-methoxycarbonyl- and a-ethoxycar-
bonyl-substituted phosphorus ylides had been studied and
were found to react with aldehydes with moderate trans
selectivity (e.g., Z/E ꢀ 15:85).[6, 7] As was found later, the E
isomer is formed almost exclusively (Z/E ꢁ 1:99) when a-
alkyl-branched, a-acyl-substituted, and a-formylated triphen-
ylphosphonio ylides (e.g., 1-methoxycarbonylethylidenetri-
phenylphosphorane,[8] acetonylidenetriphenylphosphorane,[9]
and formylmethylenetriphenylphosphorane[10, 11]) or trialkyl-
phosphonio ylides (e.g. methoxycarbonylmethylenetricyclo-
Unlike their reactive or stabilized congeners, moderated
ylides are not a uniform class of compounds (see Table 1
below). They comprise a variety of structures such as a-halo-,
a-alkoxy- or a-aryloxy-, a-alkylthio- or a-arylthio-, a-1-
alkenyl- or a-1-alkynyl-, and a-aryl- or a-heteroaryl-substi-
tuted phosphorus ylides. It is quite difficult to achieve
stereocontrol with such reagents, and progress has indeed
[*] Prof. Dr. M. Schlosser, Dr. Q. Wang, M. El Khoury
Â
Institut de Chimie organique de lꢀUniversite
Batiment de chimie (BCh)
CH-1015 Lausanne-Dorigny (Switzerland)
Ã
Fax : (‡ 41)21-692-3965
420
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Chem. Eur. J. 2000, 6, No. 3

420±426
Table 1. Survey of the Z- and E-selective options offered by Wittig and Horner± Wittig reactions.
CH
P
R
Type of ylide
a-substituent R
cis-Selective olefination
trans-Selective olefination
reactive
alkyl
salt-free protocol[1±3]
betaine ± ylide epimerization[2,3,5]
no need! (see text)
moderated
moderated
moderated
stabilized
Cl, Br, I, OCH3
2-alkenyl
(hetero)aryl
OC2H5
methoxymethoxy-armed ylides[47]
‡
methoxymethoxy-armed ylides: present work
methoxymethoxy-armed ylides[46]
in methanol;[23±30] PO ylides[16±22, 31, 32]
alkyl P ylides;[38, 39] PO ylides[40, 41]
no need! (see text)
‡
alkyl P ylides;[2, 6±8] PO ylides[13±16, 33±36]
been slow in this area. As far as the trans selectivity is
concerned, it was not urgent to act. Stereomixtures of
stilbene-type alkenes can be easily and quantitatively con-
verted into the pure E isomers by any radical-chain-triggering
photochemical process. The treatment of b-substituted vinyl
halides with the required amount of an alkoxide allows the
selective destruction of the Z isomer (by antiperiplanar
elimination) and isolation of the unconsumed E compo-
nent.[37] Using allyl-, 2-methylallyl-, crotyl- and prenyl- (3-
methyl-2-butenyl-), geranyl- and cinnamylphosphonium salts
prepared from alkyldiphenylphosphanes[38] or tributylphos-
phane,[39] it was possible to make dienes having Z/E ratios in
the range of 12:88 ± 2:98 with respect to the newly formed
double bond. Thus, the finding of a more convenient, more
general and more selective access to (E)-dienes by Wittig ±
Horner reaction with a-deprotonated allylic diphenylphos-
phine oxides[40] and phosphonates[41] was certainly welcome
but not indispensable. The situation was far more critical on
the other side. The only case of notable cis selectivity
experienced with a moderated ylide concerned the olefination
of aldehydes with triphenylphosphonio-2-(sodiooxycarbon-
yl)-2-propenide[42] with reported Z/E ratios of >95:5.
As suggested by the ªpropeller modelº mechanism[43] of the
Wittig reaction, a systematic investigation had confirmed that
ortho substituents at the ªstationaryº rings attached to the
phosphorus atom can considerably enhance the cis selectivity
of reactive ylides.[44, 45] Following this lead, we developed
tris(2-methoxymethoxyphenyl)phosphonio(arylmethanides) as
tailor-made Wittig reagents for the synthesis of Z stilbenes.[46]
The Z/E ratios achieved with these ªmethoxymethoxy-
armedº benzylic ylides ranged from 93:7 to 96:4 in typical
cases.[47]
Results and Discussion
We have now turned to methoxymethoxy-armed allylic ylides
to access conjugated Z dienes. Tris(2-methoxymethoxyphen-
yl)phosphonio-2-propenide [allylidenetris(2-methoxymeth-
oxyphenyl)phosphorane] was found to react with saturated
and a,b-unsaturated aliphatic and aromatic aldehydes to
afford the corresponding products (1a, 2a, 4a, 8a ± 10a; see
Scheme 1 and Table 2) in poor yields (10 ± 46%, on the
O
O
O
O
................
P−CH−CH−CH2
R−CH=O
R−CH=O
R−CH=O
+
R−C=C−CH=CH2
H H
3
1a - 10a
O
................
P−CH−C−C−CH3
H
H
R−C=C−C=C−CH3
H H H
+
H
3
1b - 10b
O
...................
P−CH−CH−C(CH3)2
+
R−C=C−CH=C(CH3)2
H H
3
1c - 10c
Scheme 1. Reaction of methoxymethoxy-armed ylides with aldehydes to
furnish the products 1 ± 10.
average 27%) but with excellent cis selectivities (Z/E ratios
around 98:2). Tris(2-methoxymethoxyphenyl)phosphonio-
2(E)-butenide [crotylidenetris(2-methoxymethoxyphenyl)-
phosphorane] and tris(2-methoxymethoxyphenyl)phospho-
nio-3-methyl-2-butenide [prenylidenetris(2-methoxymethoxy-
phenyl)phosphorane] gave the olefins 1b ± 4b, 9b ± 10b, and
1c ± 10c in better yields (on average 49% and 45%,
respectively) though with somewhat lower stereoselectivity
(Z/E ratios of about 95:5; see Table 2).
Good stereoselectivity can only be achieved at very low
temperatures. The reaction between benzaldehyde and the
prenylphosphonium-derived ylide, a typical case, may exem-
plify this. The product 9c is formed at ‡25, 25, 50, 75,
and 1008C in Z/E ratios of 59:41, 79:21, 84:16, 89:11, and
99:1, respectively.
Abstract in German: Behandelt man 2-Alkenyltris(2-meth-
oxymethoxyphenyl)phosphonium-Salze (2-Alkenyl ˆ Allyl,
Crotyl oder Prenyl) nacheinander mit einer starken Base
(Butyllithium oder Natriumamid) und einem gesättigten oder
ungesättigten Aldehyd, so entstehen konjugierte Diene mit
Z/E-Verhältnissen von 90:10 bis >99:1 (im Durchschnitt 96:4).
Die sperrigen Aryl-Gruppen behindern die Addukt-Bildung
zwischen Aldehyd und Ylid, weshalb sich nur mäûige Aus-
beuten erzielen lassen (meist um 45%; Extremwerte 10 ± 79%).
Das als Nebenprodukt anfallende Tris(2-methoxymethoxyphe-
nyl)phosphinoxid läût sich leicht abtrennen und sodann zum
Phosphin reduzieren oder zum wasserlöslichen Tris(2-hydro-
xyphenyl)phosphinoxid hydrolysieren.
The standard Wittig reagents provide better yields through-
out, but inferior stereoselectivities. The preparation of
(3Z,5E)-1,3,5-undecatriene[49, 50] (4a, aldehyde R'' ˆ H9C4), a
stereoisomer of galbanum constituents[49] and of a brown
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421

M. Schlosser et al.
FULL PAPER
Table 2. Reaction between three methoxymethoxy-armed phosphorus ylides [R' ˆ 2-methoxymethoxyphenyl] of the allyl type and a variety of aldehydes at
1008C: Z/E ratios at the newly formed double bond and, in parentheses, product yields.
‡
‡
‡
[a]
ˆ
ˆ
ˆ
ˆ
R CH O
R3' P CH CH CH2
R3' P CH CH CH CH3
R3' P CH CH C(CH3)2
ˆ
H13C6 CH O
(H5C2)2CH CH O
1a 98:2 (12%)
2a 99:1 (22%)
3a[b] ± (0%)
1b 93:7 (34%)
2b 94:6 (47%)
3b[c] 100:0 (81%)
4b[e] 90:10 (25%)
1c 93:7 (32%)
2c 93:7 (12%)
3c[c] 96: 4 (47%)
4c[e, f] 96:4 (25%)
5c 92:8 (36%)
6c 91:9 (22%)
7c 90:10 (47%)
8c 97:3 (75%)
9c 99:1 (79%)
10c 99:1 (71%)
ˆ
ˆ
(H3C)3C CH O
R''CH2 CH CH CH O
4a[d] 98:2 (10%)
ˆ
ˆ
H11C5 CH CH CH CH CH O
5a[g]
6a[g]
7a[g]
±
±
±
5b[g]
6b[g]
7b[g]
8b[g]
±
±
±
±
ˆ
ˆ
ˆ
ˆ
ˆ
H9C4 CH C(C3H7) CH O
ˆ
ˆ
(H3C)2C CH CH O
ˆ
H3CO C6H4 CH O (p)
8a 97:3 (34%)
9a 97:3 (46%)
10a 98:2 (35%)
ˆ
C6H5 CH O
9b 98:2 (54%)
10b 95:5 (50%)
ˆ
NC C6H4 CH O (p)
[a] E !Z Isomerization of the existing double bond in the crotyl chain occurred in the course of the reaction to the extent of 0 ± 8%. Under standard
reaction conditions, (E)-triphenylphosphonio-2-butenide (crotylidenetriphenylphosphorane)[48] gives rise to considerably more stereorandomization. [b] No
5,5-dimethyl-1,3-hexadiene (3a) was identified, but a derivative (12; see text) was isolated in 82% yield. [c] Reaction performed at 758C rather than
1008C. [d] (E)-2-Octenal (R'' ˆ C4H9) was used as the carbonyl component to afford (3Z,5E)-1,3,5-undecatriene (see also text). [e] (E)-2-Hexenal (R'' ˆ
C2H5) was used as the carbonyl component to afford (2E,4Z,6E)-2,4,6-decatriene or (2E,4Z,6E)-2-methyl-2,4,6-decatriene. [f] When (E)-2-nonenal (R'' ˆ
C5H11) was used as the carbonyl component, the (2Z,4E,6E) and (2E,4E,6E) isomers of 2-methyl-2,4,6-tredecatriene (28%) were obtained in a ratio of
94:6. [g] The preparation was not attempted.
algae gametoattractant,[50] is a typical illustration (Scheme 2).
The triphenylphosphonio-2-propenide and (E)-2-octenal gave
R'3P−CH−CH−CH2
α
γ
a 70:30 (3Z,5E) and (3E,5E) mixture in 37% yield, whereas
the methoxymethoxy-armed ylide provided a 98:2 isomeric
ratio, although in only a 10% yield. The steric congestion in
O
CH−C(CH3)3
R'3P−CH−CH=CH2
O−CH−C(CH3)3
R'3P−CH=CH−CH2
X
O
+
P
3
H9C4
OH
CH−C(CH3)3
R'3P−CH−CH=CH2
O−CH−C(CH3)3
R'3P−CH−CH−CH
11
H9C4
H9C4
OH
(3E,5E)-4a
(3Z,5E)-4a
H
CH−C(CH3)3
(H3C)3C−CH=CH−CH=CH2
R'3P−CH−C=C−H
O−CH−C(CH3)3
Scheme 2. Stereoselective preparation of 1,3,5-undecatriene (4a).
3a
the vicinity of the ylide a-carbon atom is at the origin of the
unsatisfactory degree of olefination. The methoxymethoxy-
armed ylide and the aldehyde, whatever its individual
structure, combine at 1008C or even at 758C extremely
slowly, as witnessed by the time (about 1 h) required for the
complete decoloration of the reaction mixture. In the mean-
while, base-catalyzed self-transformations (mainly aldol con-
densation or Cannizzaro and Tishchenko redox processes)
may consume a significant amount of the carbonyl compo-
nent. Moreover, when the aldehyde does become attached to
the ylide, this may occur at the unhindered g-position rather
than at the a-position.[51] Actually, this appears to be the
favored reaction mode at least of the parent ylide. When
tris(2-methoxymethoxyphenyl)phosphonio-2-propenide was
treated at 1008C with pivalaldehyde and the mixture was
gradually warmed to 258C where it was kept for 2 h, no trace
of the direct olefination product 3a was detected, but 86% of
compound 12 was isolated (Scheme 3). As shown by the
incorporation of two tert-butyl groups, the formation of the
dienol 12 must have been preceded by an initial g-addition of
pivalaldehyde. Then tautomerization of the resulting ene-
phosphonio-alkoxide to a new allylic phosphorus ylide 11
OH
OH
H
CH−C(CH3)3
H
(H3C)3C−C=C−C=C−CH−C(CH3)3
R'3P−CH−C=C−H
H
H
H
O−CH−C(CH3)3
12
Scheme 3. Addition at the g- rather than the a-position of the allyl group,
illustrated by the favored formation of compound 12.
occurred by intra- or intermolecular deprotonation. The new
intermediate 11 eventually reacted with a second molecule of
pivalaldehyde to afford the final product 12.
The ortho substitution of the ªstationaryº phenyl parts of
the ylide has once more proven an efficacious means to boost
cis selectivity. On the basis of previous work,[44] other
substituents such as fluoro or methyl can be expected to act
in the same way. The methoxymethoxy group offers the
advantage of facile preparation of the triarylphosphane
starting material. Moreover, the tris(2-methoxymethoxyphen-
yl)phosphine oxide by-product can be readily extracted from
the reaction mixture after acid hydrolysis to the trisphenol.
Alternatively, it may be isolated and converted back to the
phosphane by reduction with aluminum hydride.[52]
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Stereocontrolled Wittig Reactions
420±426
as the aldehyde component. According to gas chromatography (30 m, DB-
1, 808C; 30 m, DB-WAX, 808C; dodecane as internal standard), product 4a
was formed in 10% yield and the newly formed double bond with a Z/E
ratio of 98:2. The reaction mixture was poured into water (50 mL) and
extracted with hexanes (2 Â 25 mL). The combined organic layers were
washed with brine (25 mL), dried, and concentrated. Upon distillation a
light yellow liquid was isolated; b.p. 68 ± 708C/3 Torr (ref. [56]: b.p. 638C/
2.2 Torr); n2D0 1.5134 (ref. [56]: n2D0 1.5122); 1H NMR: d ˆ 6.80 (dt, J ˆ 16.8,
10.3 Hz, 1H), 6.49 (ddm, J ˆ 14.9, 11.0 Hz, 1H), 5.97 (t, J ˆ 10.9 Hz, 1H),
5.87 (t, J ˆ 11.0 Hz, 1H), 5.72 (dt, J ˆ 14.9, 7.2 Hz, 1H), 5.19 (d, J ˆ 16.8 Hz,
1H), 5.09 (d, J ˆ 10.2 Hz, 1H), 2.12 (q, J ˆ 7.2 Hz, 2H), 1.4 (m, 2H), 1.3 (m,
4H), 0.88 (t, J ˆ 7.1 Hz, 3H).
(Z)-1-(4-Methoxyphenyl)-1,3-butadiene (8a): At 258C, a suspension of
sodium amide (1.0 g, 25 mmol), potassium tert-butoxide (0.3 g, 2.5 mmol),
and 2-propenyltris(2-methoxymethoxyphenyl)phosphonium bromide
(14.0 g, 25 mmol) in tetrahydrofuran (0.12 L) was stirred vigorously for
1 h. At 1008C, anisaldehyde (3.0 mL, 3.4 g, 25 mmol) was added. After
6 h of stirring at 1008C, 34% of 8a with a Z/E composition of 97:3 was
detected by gas chromatography (3 m, 5% C-20M, 1508C; 3 m, 5% SE-30,
1508C; tetradecane as internal standard). The reaction mixture was
absorbed on silica gel (25 mL) and evaporated to dryness. The powder
was poured on top of a column filled with more silica gel (100 mL) and
eluted with hexanes. The product was crystallized as colorless needles; m.p.
32 ± 358C (ref. [57]: m.p. 468C); b.p. 68 ± 708C/2 Torr (ref. [57]: b.p. 1248C/
6 Torr); n2D0 1.5963; 1H NMR: d ˆ 7.26 (symm. m, 2H), 6.9 (m, 3H), 6.39 (d,
J ˆ 11.5 Hz, 1H), 6.18 (t, J ˆ 11.5 Hz, 1H), 5.34 (d, J ˆ 17.0 Hz, 1H), 5.19 (d,
J ˆ 10.5 Hz, 1H), 3.81 (s, 3H).
Experimental Section
For standard operations and abbreviations see recent publications from this
laboratory.[53] Proton nuclear magnetic resonance spectra were recorded at
400 MHz, the samples having been dissolved in deuterochloroform. The
stationary phases employed for gas chromatography were silicon rubbers
(SE-30, DB-1, DB-1701, and DB-210), polyethylene glycols (C-20M, DB-
WAX, and DB-FFAP), and Apiezon-L hydrocarbon grease (AP-L).
1. Starting materials
2-Propenyltris(2-methoxymethoxyphenyl)phosphonium bromide: Allyl
bromide (3-bromopropene; 9.3 mL, 12 g, 0.11 mol) and tris(2-methoxy-
methoxyphenyl)phosphane[45, 46] (44 g, 0.10 mol) were dissolved in toluene
(0.80 L). After 1 h at 508C, the fine white powder formed was collected by
filtration, washed with diethyl ether and dried; 52 g (92%); m.p. 137 ±
1398C (decomp); 1H NMR: d ˆ 7.72 (tt, J ˆ 8.5, 1.5 Hz, 3H), 7.46 (ddd, J ˆ
15.0, 7.9, 1.5 Hz, 3H), 7.38 (ddd, J ˆ 8.5, 5.6, 0.7 Hz, 3H), 7.25 (tdd, J ˆ 7.9,
2.6, 0.9 Hz, 3H), 5.62 (m, 2H), 5.3 (m, 1H), 5.22 (s, 6H), 4.36 (dd, J ˆ 16.5,
6.2 Hz, 2H), 3.14 (s, 9H); [C27H32O6P]Br (563.42): calcd C 57.56, H 5.72;
found C 57.74, H 5.74.
(E)-2-Butenyltris(2-methoxymethoxyphenyl)phosphonium bromide: Ob-
tained in the same way from (E)-2-butenyl bromide (1-bromo-2-butene;
2.6 mL, 3.4 g, 25 mmol)[54] and tris(2-methoxymethoxyphenyl)phos-
phane[45, 46] (11 g, 25 mmol); 13.1 g (91%); m.p. 181 ± 1838C (decomp);
1H NMR: d ˆ 7.73 (tt, J ˆ 7.7, 1.6 Hz, 3H), 7.51 (ddd, J ˆ 14.8, 7.7, 1.6 Hz,
3H), 7.37 (dd, J ˆ 8.1, 5.9 Hz, 3H), 7.26 (td, J ˆ 7.7, 2.7 Hz, 3H), 6.1 (m, 1H),
5.01 (s, 6H), 5.1 (m, 1H), 4.30 (dd, J ˆ 15.9, 7.0 Hz, 2H), 3.14 (s, 9H), 1.54
(tm, J ˆ 5.6 Hz, 3H); [C28H34O6P]Br (577.45): calcd C 58.24, H 5.93; found
C 58.23, H 5.80.
(Z)-1-Phenyl-1,3-butadiene (9a): In the same way as described in the
preceding paragraph,
a reaction with benzaldehyde (2.5 mL, 2.7 g,
3-Methyl-2-butenyltris(2-methoxymethoxyphenyl)phosphonium bromide:
Obtained analogously from 3-methyl-2-butenyl bromide (prenyl bromide,
1-bromo-3-methyl-2-butene; 13 mL, 16 g, 0.11 mol) and tris(2-methoxy-
methoxyphenyl)phosphane;[45, 46] 52 g (87%); m.p. 158 ± 1608C (decomp);
1H NMR: d ˆ 7.75 (tt, J ˆ 7.8, 1.6 Hz, 3H), 7.4 (m, 6H), 7.30 (tdd, J ˆ 7.5, 3.6,
1.4 Hz, 3H), 5.16 (s, 6H), 4.8 (m, 1H), 4.06 (dd, J ˆ 16.6, 6.9 Hz, 2H), 3.15
(s, 9H), 1.75 (d, J ˆ 1.7 Hz, 3H), 1.64 (dd, J ˆ 4.4, 1.5 Hz, 3H);
[C29H36O6P]Br (591.47): calcd C 58.89, H 6.13; found C 59.01, H 5.91.
25 mmol) was performed to give 46% of 9a in a Z/E ratio of 97:3 (by gas
chromatography: 3 m, 5% C-20M, 1208C; 3 m, 5% SE-30, 1408C;
dodecane as internal standard). Extraction and distillation afforded
colorless liquid; b.p. 92 ± 948C/15 Torr (ref. [58]: b.p. 718C/11 Torr); nD20
1.6088 (ref. [58]: n2D5 1.5822); 1H NMR: d ˆ 7.3 (m, 5H), 6.88 (dtd, J ˆ 16.9,
10.2, 1.1 Hz, 1H), 6.44 (d, J ˆ 11.6 Hz, 1H), 6.25 (d, J ˆ 11.6 Hz, 1H), 5.36
(d, J ˆ 16.9 Hz, 1H), 5.21 (d, J ˆ 10.2 Hz, 1H).
(Z)-1-(4-Cyanophenyl)-1,3-butadiene (10a): Analogously, 4-cyanobenzal-
dehyde (3.3 g, 25 mmol) gave 46% of 10a in a Z/E ratio of 97:3 (by gas
chromatography: 3 m, 5% C-20M, 1508C; 3 m, 5% SE-30, 1508C;
tetradecane as internal standard). After purification by column chroma-
tography (eluent: hexanes), the product was obtained as colorless platelets;
2. cis-Selective Wittig reactions
(Z)-1,3-Decadiene (1a): At 258C, a suspension of sodium amide (1.0 g,
25 mmol), potassium tert-butoxide (0.3 g, 2.5 mmol), and 2-propenyltris(2-
methoxymethoxyphenyl)phosphonium bromide (14.0 g, 25 mmol) in tetra-
hydrofuran (0.12 L) was stirred vigorously for 1 h. At 1008C, heptanal
(3.5 mL, 2.9 g, 25 mmol) was added. After 6 h of stirring at 1008C, an
aliquot of the reaction mixture was analyzed by gas chromatography (30 m,
DB-1701, 608C; 30 m, DB-FFAP, 608C; decane as internal standard).
Products 1a was found to be present in 12% yield and as a Z/E mixture in
the ratio of 98:2. The reaction mixture was poured into water (50 mL) and
extracted with hexanes (2 Â 25 mL). The combined organic layers were
washed with brine (25 mL), dried, and concentrated. Upon distillation the
product was collected as a colorless liquid; b.p. 75 ± 768C/10 Torr; n2D0 1.4385
(ref. [55]: n2D0 1.4551); 1H NMR: d ˆ 6.31 (dt, J ˆ 17.0, 10.2 Hz, 1H), 6.00 (t,
J ˆ 10.7 Hz, 1H), 5.45 (dt, J ˆ 10.7, 7.1 Hz, 1H), 5.07 (dm, J ˆ 17.0 Hz, 1H),
4.95 (dm, J ˆ 10.2 Hz, 1H), 2.07 (q, J ˆ 7.1 Hz, 2H), 1.3 (m, 8H), 0.85 (t, J ˆ
7.0 Hz, 3H).
1
m.p. 67 ± 698C (ref. [59] m.p. 51.5 ± 52.08C); H NMR: d ˆ 7.6 (m, 2H), 7.4
(m, 2H), 6.79 (dt, J ˆ 16.9, 10.2 Hz, 1H), 6.44 (d, J ˆ 11.2 Hz, 1H), 6.37 (dd,
J ˆ 11.2, 10.2 Hz, 1H), 5.48 (d, J ˆ 16.9 Hz, 1H), 5.34 (d, J ˆ 10.2 Hz, 1H).
(2E,4Z)-2,4-Undecadiene (1b): At 758C, a solution of butyllithium
(25 mmol) in hexanes (17 mL) was added to a suspension of (E)-2-
butenyltris(2-methoxymethoxyphenyl)phosphonium bromide (14.4 g,
25 mmol) in tetrahydrofuran (0.12 L). After 30 min of vigorous stirring at
08C, a clear, deep red solution was obtained. At 1008C, heptanal (3.5 mL,
2.9 g, 25 mmol) was added. After 6 h of stirring at 1008C, an aliquot of
the reaction mixture was analyzed by gas chromatography (30 m, DB-1701,
808C; 30 m, DB-FFAP, 658C; undecane as internal standard), which
indicated the formation of product 1b in 34% yield and in a 93:7 Z/E ratio
(at the new double bond). The reaction mixture was poured into water
(50 mL) and extracted with hexanes (2 Â 25 mL). The combined organic
layers were washed with brine (25 mL), dried, and concentrated. Upon
distillation a colorless liquid was collected; b.p. 81 ± 828C/10 Torr; nD20
1.4626; 1H NMR:[60] d ˆ 6.33 (ddm, J ˆ 15.0, 10.8 Hz, 1H), 5.95 (t, J ˆ
10.8 Hz, 1H), 5.67 (symm. m, 1H), 5.30 (dt, J ˆ 10.8, 7.5 Hz, 1H), 2.18 (q,
J ˆ 7.5 Hz, 2H), 1.79 (d, J ˆ 7.1 Hz, 3H), 1.3 (m, 8H), 0.88 (t, J ˆ 6.9 Hz,
3H).
(Z)-5-Ethyl-1,3-heptadiene (2a): At 758C, a solution of butyllithium
(25 mmol) in hexanes (17 mL) was added to a suspension of 2-propenyl-
tris(2-methoxymethoxyphenyl)phosphonium bromide (14.0 g, 25 mmol) in
tetrahydrofuran (0.12 L). After 30 min of vigorous stirring at 08C, a clear,
deep red solution was obtained. At 1008C, it was treated with 2-ethyl-
butyraldehyde (3.1 mL, 2.5 g, 25 mmol). After 6 h of stirring at 1008C,
gas chromatographic analysis (30 m, DB-1701, 408C; 30 m, DB-FFAP,
358C; nonane as internal standard) revealed the presence of 22% of 2a;
Z/E ˆ 99:1. The product was extracted as described above. Distillation
afforded a colorless liquid; b.p. 30 ± 318C/10 Torr; n2D0 1.4510; 1H NMR: d ˆ
6.62 (dtd, J ˆ 16.7, 10.5, 1.1 Hz, 1H), 6.06 (tm, J ˆ 10.5 Hz, 1H), 5.16 (ddt,
J ˆ 16.7, 2.1, 0.7 Hz, 1H), 5.12 (t, J ˆ 10.5 Hz, 1H), 5.04 (d, J ˆ 10.5 Hz,
1H), 2.3 (m, 1H), 1.4 (m, 2H), 1.2 (m, 2H), 0.84 (t, J ˆ 7.3 Hz, 6H); C9H16
(124.23): calcd C 87.02, H 12.98; found C 87.12, H 12.88.
(2E,4Z)-6-Ethyl-2,4-octadiene (2b): Analogously, 2-ethylbutyraldehyde
(3.1 mL, 2.5 g, 25 mmol) was converted into 47% of 2b having a (4Z/4E)
ratio of 94:6 (by gas chromatography: 30 m, DB-1701, 308C; 30 m, DB-
WAX, 258C; decane as internal standard). Extraction and distillation
afforded a colorless liquid; b.p. 95 ± 968C/80 Torr; n2D0 1.4587; 1H NMR: d ˆ
6.30 (ddm, J ˆ 14.9, 11.1 Hz, 1H), 6.02 (dd, J ˆ 11.1, 10.6 Hz, 1H), 5.65 (dq,
J ˆ 14.9, 6.8 Hz, 1H), 4.97 (dd, J ˆ 10.6, 9.6 Hz, 1H), 2.28 (dquint, J ˆ 9.6,
4.7 Hz, 1H), 1.73 (dd, J ˆ 6.8, 1.1 Hz, 3H), 1.4 (m, 2H), 1.2 (m, 2H), 0.84 (t,
(3Z,5E)-1,3,5-Undecatriene (4a): The reaction was carried out exactly as
described in the preceding paragraph using (E)-2-octenal (3.2 g, 25 mmol)
Chem. Eur. J. 2000, 6, No. 3
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0603-0423 $ 17.50+.50/0
423

M. Schlosser et al.
FULL PAPER
J ˆ 7.5 Hz, 6H); C10H18 (138.25): calcd C 86.88, H 13.12; found C 87.18, H
colorless liquid; b.p. 67 ± 698C/10 Torr; n2D0 1.4714; 1H NMR: d ˆ 6.24 (t,
J ˆ 10.8 Hz, 0.9H), 6.17 (dd, J ˆ 15.2, 10.6 Hz, 0.1H), 6.06 (d, J ˆ 10.8 Hz,
0.9H), 5.81 (d, J ˆ 10.6 Hz, 0.1H), 5.29 (dd, J ˆ 15.2, 8.9 Hz, 0.1H), 5.02 (t,
J ˆ 10.8 Hz, 0.9H), 2.3 (m, 1H), 1.80 (s, 2.7H), 1.76 (s, 2.7H), 1.75 (s, 0.5H),
1.5 (m, 2H), 1.2 (m, 2H), 0.85 (t, J ˆ 7.5 Hz, 6H); C11H20 (152.28): calcd C
86.76, H 13.24; found C 86.82, H 13.08.
12.74.
(2E,4Z)-6,6-Dimethyl-2,4-heptadiene (3b): In the same way, pivalaldehyde
(2.8 mL, 2.2 g, 25 mmol) gave 81% of 3b having a (4Z/4E) ratio of ꢂ 99:1
(by gas chromatography: 30 m, DB-1701, 308C; 30 m, DB-WAX, 258C;
nonane as internal standard). Upon extraction and distillation, a colorless
liquid[61] was isolated; b.p. 78 ± 818C/95 Torr; n2D0 1.4578; 1H NMR: d ˆ 6.55
(dd, J ˆ 14.7, 11.9 Hz, 1H), 5.81 (t, J ˆ 11.9 Hz, 1H), 5.62 (dq, J ˆ 14.7,
6.6 Hz, 1H), 5.26 (d, J ˆ 11.9 Hz, 1H), 1.79 (dd, J ˆ 6.6, 1.5 Hz, 3H), 1.17 (s,
9H).
(4Z)-2,6,6-Trimethyl-2,4-heptadiene (3c):
A solution of butyllithium
(25 mmol) in hexanes (17 mL) was added to a suspension of 3-methyl-2-
butenyltris(2-methoxymethoxyphenyl)phosphonium bromide (14.8 g,
25 mmol) in tetrahydrofuran (0.10 L) at 758C. After 30 min of vigorous
stirring at 08C, a clear, deep red solution was obtained. At 758C,
pivalaldehyde (2.8 mL, 2.2 g, 25 mmol) was added. After 6 h of stirring at
758C, 47% of 3c having a (4Z/4E) ratio 96:4 was detected by gas
chromatography (30 m, DB-1701, 408C; 30 m, DB-FFAP, 408C; decane as
internal standard). After extraction and distillation a colorless liquid was
collected; b.p. 75 ± 778C/40 Torr; n2D0 1.4684; 1H NMR:[39] d ˆ 6.29 (d, J ˆ
12.1 Hz, 1H), 5.99 (t, J ˆ 12.1 Hz, 1H), 5.29 (d, J ˆ 12.1 Hz, 1H), 1.80 (s,
3H), 1.72 (s, 3H), 1.16 (s, 9H).
(2E,4Z,6E)-2,4,6-Decatriene (4b): With (E)-2-hexenal (2.9 mL, 2.5 g,
25 mmol) as the aldehyde component, 25% of 4b having a (4Z/4E) ratio
of 90:10 was obtained (according to gas chromatography: 30 m, DB-1701,
508C; 50 m, Megasolve, 708C; decane as internal standard). Extraction and
distillation afforded a light yellow liquid; b.p. 92 ± 968C/30 Torr (ref. [62]
1
b.p. 568C/4 Torr); n2D0 1.5196; H NMR: d ˆ 6.5 (m, 2H), 5.8 (m, 2H), 5.7
(m, 2H), 2.1 (m, 2H), 1.80 (dd, J ˆ 7.0, 1.5 Hz, 2H), 1.43 (symm. m, 1H),
0.92 (t, J ˆ 7.4 Hz, 3H).
(4Z,6E)-2-Methyl-2,4,6-decatriene (4c): At 258C, a suspension of sodium
amide (1.0 g, 25 mmol), potassium tert-butoxide (0.3 g, 2.5 mmol) and
3-methyl-2-butenyltris(2-methoxymethoxyphenyl)phosphonium bromide
(14.8 g, 25 mmol) in tetrahydrofuran (0.12 L) was stirred vigorously for
1 h. At 1008C, (E)-2-hexenal (2.9 mL, 2.5 g, 25 mmol) was added. After
(1Z,3E)-1-Phenyl-1,3-pentadiene (9b): At 258C, a suspension of sodium
amide (1.0 g, 25 mmol), potassium tert-butoxide (0.3 g, 2.5 mmol) and (E)-
2-butenyltris(2-methoxymethoxyphenyl)phosphonium bromide (14.4 g,
25 mmol) in tetrahydrofuran (0.12 L) was stirred vigorously for 1 h. At
1008C, benzaldehyde (2.5 mL, 2.7 g, 25 mmol) was added. After 6 h of
stirring at 1008C, 54% of 9b having a Z/E ratio of 98:2 had been formed
(as determined by gas chromatography: 3 m, 6% C-20M, 1308C; 50 m,
Megasolve, 1108C; tridecane as internal standard). The reaction mixture
was poured into water (50 mL) and extracted with hexanes (2 Â 25 mL).
The combined organic layers were washed with brine (25 mL), dried and
concentrated. After extraction and distillation a colorless liquid was
collected; b.p. 104 ± 1068C/10 Torr (ref. [2]: b.p. 1068C/11 Torr); n2D0 1.5876
(ref. [2]: n2D0 1.6103); 1H NMR: d ˆ 7.3 (m, 5H), 6.61 (dd, J ˆ 15.0, 11.2 Hz,
1H), 6.29 (d, J ˆ 11.2 Hz, 1H), 6.20 (t, J ˆ 11.2 Hz, 1H), 5.88 (dt, J ˆ 15.0,
6.9 Hz, 1H), 1.80 (dd, J ˆ 6.9, 1.8 Hz, 3H).
(1Z,3E)-1-(4-Cyanophenyl)-1,3-pentadiene (10b): At 758C, a solution of
butyllithium (25 mmol) in hexanes (17 mL) was added to a suspension of
2-butenyltris(2-methoxymethoxyphenyl)phosphonium bromide (14.4 g,
25 mmol) in tetrahydrofuran (0.12 L) while this was vigorously stirred.
After 30 min at 08C, a clear, deep red solution was obtained. At 1008C,
4-cyanobenzaldehyde (3.3 g, 25 mmol) was added. After 6 h of stirring at
1008C, the reaction mixture contained 50% of 10b having a Z/E
composition of 95:5 (gas chromatographic analysis: 30 m, DB-1701, 1508C;
30 m, DB-FFAP, 1508C; tridecane as internal standard). After extraction
(see above) and upon distillation, a light yellow liquid was isolated; b.p.
108 ± 1118C/0.5 Torr; m.p. 25 ± 288C; 1H NMR: d ˆ 7.60 (d, J ˆ 8.2 Hz,
1.9H), 7.55 (d, J ˆ 8.5 Hz, 0.1H), 7.42 (d, J ˆ 8.5 Hz, 0.1H), 7.39 (d, J ˆ
8.2 Hz, 1.9H), 6.83 (dd, J ˆ 15.8, 10.4 Hz, 0.05H), 6.53 (ddq, J ˆ 15.0, 10.9,
1.6 Hz, 0.95H), 6.40 (d, J ˆ 15.6 Hz, 0.05H), 6.31 (t, J ˆ 11.1 Hz, 0.95H),
6.24 (d, J ˆ 11.2 Hz, 0.95H), 6.22 (dd, J ˆ 15.6, 10.4 Hz, 0.05H), 6.0 (m,
1H), 1.86 (d, J ˆ 6.8 Hz, 0.15H), 1.82 (dd, J ˆ 6.8, 1.3 Hz, 2.85H); C12H11N
(169.23): calcd C 85.17, H 6.55; found C 84.54, H 6.39.
6 h of stirring at
1008C, the reaction mixture was found by gas
chromatographic analysis (55 m, AP-L, 1358C) to contain 25% of 4c in a
(4Z/4E) ratio of 96:4. After chromatographic purification (see above;
preparation of 8a), a light yellow liquid[63] was isolated; b.p. 67 ± 698C/
10 Torr; n2D0 1.4714; 1H NMR: d ˆ 6.30 (dm, J ˆ 12.0 Hz, 1H), 6.1 (m, 1H),
6.05 (d, J ˆ 11.5 Hz, 1H), 5.8 (m, 1H), 5.69 (hept, J ˆ 7.3 Hz, 1H), 2.11
(quint, J ˆ 8.5 Hz, 2H), 1.85 (s, 3H), 1.78 (s, 3H), 1.4 (m, 2H), 0.99 (td, J ˆ
7.4, 3.0 Hz, 3H).
When (E)-2-nonenal (4.1 mL, 3.5 g, 25 mmol) was used as the carbonyl
component, the (4Z,6E) and (4E,6E) isomers of 2-methyl-2,4,6-trideca-
triene[64] (28%) were analogously obtained in a 94:6 ratio and a total yield
of 28% (by gas chromatography: 45 m, OV-17, 1658C; 30 m, DB-1, 1408C);
1H NMR: d ˆ 6.3 (m, 1H), 6.1 (m, 2H), 5.80 (d, J ˆ 10.6 Hz, 1H), 5.69 (oct,
J ˆ 6.6 Hz, 1H), 2.11 (quint, J ˆ 6.6 Hz, 2H), 1.83 (s, 3H), 1.76 (s, 3H), 1.3
(m, 8H), 0.9 (3H, m).
(4Z,6E,8E)-2-Methyl-2,4,6,8-tetradecatetraene (5c): In the same way,
(2E,4E)-2,4-decadienal (4.4 mL, 3.8 g, 25 mmol) afforded 36% of 5c
having a (4Z/4E) ratio of 92:8 as determined by gas chromatography (45 m,
OV-17, 1608C; 30 m, DB-1, 1608C). Upon column chromatography (see
above), a light yellow liquid was obtained; m.p. 42 to 388C; b.p. 80 ±
858C/0.6 Torr; n2D0 1.5877; 1H NMR: d ˆ 6.2 (m, 5H), 5.8 (m, 1H), 5.7 (hex,
J ˆ 7.1 Hz, 1H), 2.11 (q, J ˆ 7.6 Hz, 2H), 1.83 (s, 3H), 1.77 (s, 3H), 1.3 (m,
6H), 0.9 (m, 3H); C15H24 (204.35): calcd C 88.16, H 11.84; found C 88.14, H
11.87.
(4Z,6E)-2-Methyl-6-propyl-2,4,6-undecatriene (6c): Analogously, (E)-2-
propyl-2-heptenal (4.5 mL, 3.9 g, 25 mmol) gave 22% of 6c having a (4Z/
4E) ratio of 91:9 as determined by gas chromatography (2 m, 7% AP-L,
2208C; 3 m, 10% C-20M, 1708C). The products were purified by column
chromatography (see above; preparation of 8a) to give a colorless liquid;
m.p. 68 to 648C; b.p. 86 ± 888C/0.6 Torr; n2D0 1.5420; 1H NMR: d ˆ 6.33
(dd, J ˆ 15.5, 11.0 Hz, 0.1H), 6.25 (d, J ˆ 10.4 Hz, 1.8H), 6.15 (d, J ˆ
11.4 Hz, 0.9H), 6.00 (d, J ˆ 15.5 Hz, 0.1H), 5.85 (d, J ˆ 10.9 Hz, 0.1H),
5.67 (d, J ˆ 11.1 Hz, 0.9H), 5.42 (t, J ˆ 7.5 Hz, 0.1H), 2.2 (m, 2H), 1.8 (m,
6H), 1.4 (m, 6H), 0.9 (m, 6H); C15H26 (206.37): calcd C 87.30, H 12.70;
found C 87.05, H 12.69.
(4Z)-2-Methyl-2,4-undecadiene (1c): At 258C, a suspension of sodium
amide (1.0 g, 25 mmol), potassium tert-butoxide (0.3 g, 2.5 mmol) and
3-methyl-2-butenyltris(2-methoxymethoxyphenyl)phosphonium bromide
(14.8 g, 25 mmol) in tetrahydrofuran (0.12 L) was stirred vigorously for
1 h. At 1008C, heptanal (3.5 mL, 2.9 g, 25 mmol) was added. After 6 h of
stirring at 1008C, 32% of 1c with a Z/E ratio of 93:7 had formed
(determined by gas chromatography: 30 m, DB-1701, 1108C; 30 m, DB-
FFAP, 808C; undecane as internal standard). Extraction and distillation
afforded a colorless liquid; b.p. 125 ± 1278C/25 Torr; m.p. 69 to 678C;
n2D0 1.4722; 1H NMR: d ˆ 6.21 (ddt, J ˆ 15.1, 10.6, 1.4 Hz, 0.1H), 6.16 (t, J ˆ
10.6 Hz, 0.9H), 6.07 (d, J ˆ 10.6 Hz, 0.9H), 5.79 (d, J ˆ 10.6 Hz, 0.1H), 5.56
(dt, J ˆ 15.1, 7.2 Hz, 0.1H), 5.33 (dt, J ˆ 10.6, 7.7 Hz, 0.9H), 2.16 (q, J ˆ
7.7 Hz, 1.8H), 2.08 (q, J ˆ 7.2 Hz, 0.2H), 1.81 (s, 2.7H), 1.75 (s, 0.5H), 1.74
(s, 2.7H), 1.3 (m, 8H), 0.9 (m, 3H); C12H22 (166.31): calcd C 86.67, H 13.33;
found C 86.56, H 13.23.
(4Z)-2,7-Dimethyl-2,4,6-octatriene (7c): Analogously, 3-methylcrotonal-
dehyde (2.4 mL, 2.1 g, 25 mmol) was converted into 47% of 7c with a (4Z/
4E) ratio of 90:10 as found by gas chromatographic analysis (30 m, DB-
WAX, 508C; 30 m, DB-FFAP, 608C). Extraction and distillation afforded
product as light yellow platelets; m.p. 36 ± 378C; b.p. 60 ± 658C/10 Torr
(ref. [63]: b.p. 70 ± 758C/16 Torr); n2D0 1.4768 (ref. [63]: n2D0 1.475); 1H NMR:
d ˆ 6.29 (symm. m, 2H), 5.88 (symm. m, 2H), 1.80 (6H, s), 1.76 (6H, s).
(4Z)-6-Ethyl-2-methyl-2,4-octadiene (2c): As described in the preceding
paragraph, a reaction was carried out with 2-ethylbutyraldehyde (3.1 mL,
2.5 g, 25 mmol). According to gas chromatography (30 m, DB-1701, 1208C;
30 m, DB-FFAP, 808C; undecane as internal standard), 12% of 2c was
obtained in a (4Z/4E) ratio of 93:7. Extraction and distillation provided a
(Z)-4-Methyl-1-(4-methoxyphenyl)-1,3-pentadiene (8c): An analogous re-
action was performed with anisaldehyde (3.0 mL, 3.4 g, 25 mmol). Accord-
ing to gas chromatography (2 m, 10% SE-30, 2058C; 3 m, 10% C-20M,
2458C), 75% of 8c with a Z/E ratio of 97:3 was formed. Column
chromatographic purification (see above; preparation of 8a) afforded a
424
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0603-0424 $ 17.50+.50/0
Chem. Eur. J. 2000, 6, No. 3

Stereocontrolled Wittig Reactions
420±426
colorless liquid; m.p. 26 to 228C; b.p. 80 ± 838C/0.3 Torr; n2D0 1.6003;
1H NMR: d ˆ 7.31 (d, J ˆ 9.0 Hz, 2H), 6.90 (d, J ˆ 6.5 Hz, 2H), 6.3 (m, 3H),
3.83 (s, 3H), 1.84 (s, 6H); C13H16O (188.27): calcd C 82.94, H 8.57; found C
82.93, H 8.63.
25 mmol) in tetrahydrofuran (50 mL). The mixture was refluxed for
30 min, before cold, anhydrous methanol (1 mL) was added. The mixture
was filtered through Celite, which was then washed with hot tetrahydro-
furan (3 Â 20 mL). The filtrate was concentrated. After recrystallization
from diethyl ether, the product was obtained as colorless platelets; m.p.
(Z)-4-Methyl-1-phenyl-1,3-pentadiene (9c): Analogously, benzaldehyde
(2.5 mL, 2.7 g, 25 mmol) gave 79% of 9c having a Z/E ratio of 99:1 as
determined by gas chromatography (3 m, 5% AP-L, 1508C; 3 m, 5%
C-20M, 1308C). After extraction and distillation, a colorless liquid was
collected; b.p. 45 ± 488C/2 Torr (ref. [65]: b.p. 125 ± 1308C/11 Torr); nD20
1.5963 (ref. [65]: n2D0 1.5985); 1H NMR: d ˆ 7.3 (m, 4H), 7.2 (m, 1H), 6.42 (t,
J ˆ 10.9 Hz, 1H), 6.4 (m, 1H), 6.30 (d, J ˆ 10.9 Hz, 1H), 1.85 (s, 3H), 1.83 (s,
3H).
1
129 ± 1308C (ref. [45]: m.p. 128 ± 1298C); 10.5 g (95%); H NMR: d ˆ 7.30
(td, J ˆ 7.5, 1.8 Hz, 3H), 7.11 (ddd, J ˆ 7.5, 4.5, 1.0 Hz, 3H), 6.90 (t, J ˆ
7.5 Hz, 3H), 6.79 (ddd, J ˆ 7.5, 4.5, 1.8 Hz, 3H), 5.11 (s, 6H), 3.23 (s, 9H).
Acknowledgements
(Z)-1-(4-Cyanophenyl)-4-methyl-1,3-pentadiene (10c): In the same way,
4-cyanobenzaldehyde (3.3 g, 25 mmol) afforded 71% of 10c with a Z/E
ratio of 99:1 (by gas chromatographic analysis: 2 m, 10% SE-30, 2008C;
3 m, 10% C-20M, 2458C). After chromatographic purification (see above,
preparation of 8a), the product was crystallized as colorless needles; m.p.
55 ± 578C (decomp); 1H NMR: d ˆ 7.61 (dm, J ˆ 8.5 Hz, 2H), 7.41 (dm, J ˆ
8.1 Hz, 2H), 6.56 (t, J ˆ 11.5 Hz, 1H), 6.28 (d, J ˆ 11.5 Hz, 2H), 1.89 (s,
6H); C13H13N (183.25): calcd C 85.21, H 7.15; found C 85.18, H 6.97.
The work described in the present article was financially supported by the
Schweizerische Nationalfonds zur Förderung der wissenschaftlichen For-
schung (grants 20-41'887-94 and 20-49'307-96), Bern.
[1] M. Schlosser, G. Müller, K. F. Christmann, Angew. Chem. 1966, 78,
677 ± 678; Angew. Chem. Int. Ed. Engl. 1966, 5, 667 ± 668.
[2] M. Schlosser, K. F. Christmann, Liebigs Ann. Chem. 1967, 708, 1 ± 35.
[3] M. Schlosser, Top. Stereochem. 1970, 5, 1 ± 30; for later reviews, see:
B. E. Maryanoff, A. G. Reitz, Chem. Rev. 1989, 89, 863 ± 927; E.
Vedejs, M. J. Peterson, Top. Stereochem. 1994, 1 ± 157.
[4] M. Schlosser, B. Schaub, J. de Oliveira-Neto, S. Jeganathan, Chimia
1986, 40, 244 ± 245.
(4E,6Z)-2,2,8,8-Tetramethyl-4,6-nonadien-3-ol (12): A solution of butyl-
lithium (25 mmol) in hexanes (17 mL) was added to a suspension of
2-propenyltris(2-methoxymethoxyphenyl)phosphonium bromide (14.0 g,
25 mmol) in tetrahydrofuran (0.10 L) at 758C while this was stirred
vigorously. After 30 min at 08C, a clear, deep red solution was obtained. At
758C, pivalaldehyde (2.8 mL, 2.2 g, 25 mmol) was added. After 6 h of
stirring at 758C, the reaction mixture was poured into water (50 mL) and
extracted with ether (3 Â 25 mL). The combined organic layers were
washed with brine (25 mL), dried, and concentrated. Upon distillation, no
trace of 5,5-dimethyl-1,3-hexadiene was obtained (its boiling point was
supposed to be 106 ± 1078C/760 Torr[66]). Instead, the title product was
collected as a colorless liquid which, according to 1H and 13C NMR
spectroscopy as well as gas column chromatography on three columns of
different polarity (30 m, DB-1, 1008C; 30 m, DB-WAX, 1008C; 3 m, 5%
AP-L, 808C), contained exclusively (4E,6Z) isomer (>99%); b.p. 83 ±
[5] M. Schlosser, K. F. Christmann, Angew. Chem. 1966, 78, 115 ± 115;
Angew. Chem. Int. Ed. Engl. 1966, 5, 126 ± 126.
[6] H. O. House, G. R. Rasmusson, J. Org. Chem. 1961, 26, 4278 ± 4281.
[7] A. J. Speziale, D. E. Bissing, J. Am. Chem. Soc. 1963, 26, 1888 ± 1889;
A. J. Speziale, D. E. Bissing, J. Am. Chem. Soc. 1963, 26, 3878 ± 3884.
[8] J. A. Marshall, B. S. DeHoff, D. G. Cleary, J. Org. Chem. 1986, 51,
1735 ± 1741.
[9] C. D. Snyder, H. Rapoport, J. Am. Chem. Soc. 1969, 91, 731 ± 737; E.
Demole, C. Demole, Helv. Chim. Acta 1975, 58, 1867 ± 1880; P. Yates,
S. P. Douglas, Can. J. Chem. 1982, 60, 2760 ± 2765; A. Nonnenmacher,
R. Mayer, H. Plieninger, Liebigs Ann. Chem. 1983, 2135 ± 2140; J.
Matikainen, S. Kaltia, T. Hase, I. Kilpelaeinen, T. Drakenberg, A.
Annila, Tetrahedron 1993, 49, 8007 ± 8014.
1
848C/0.5 Torr; m.p. 25 ± 278C; n2D0 1.4806; 4.0 g (82%); H NMR: d ˆ 6.69
(dd, J ˆ 15.0, 11.6 Hz, 1H), 5.82 (dd, J ˆ 12.0, 11.6 Hz, 1H), 5.62 (dd, J ˆ
15.0, 7.5 Hz, 1H), 5.38 (d, J ˆ 12.0 Hz, 1H), 3.79 (d, J ˆ 7.5 Hz, 1H), 1.7 (br,
1H), 1.16 (s, 9H), 0.91 (s, 9H); 13C NMR: d ˆ 142.0, 133.6, 128.4, 126.3, 80.7,
35.1, 33.8, 31.4 (3C), 25.7 (3C); C13H24O (196.33): calcd C 79.53, H 12.32;
found C 79.17, H 12.15.
[10] H. J. Bestmann, K. Roth, M. Eltlinger, Angew. Chem. 1979, 91, 748;
Angew. Chem. Int. Ed. Engl. 1979, 18, 687.
[11] J. S. Brimacombe, R. Hanna, A. K. M. S. Kabir, F. Bennett, I. D.
Taylor, J. Chem. Soc. Perkin Trans. 1 1986, 815 ± 821.
3. Recovery of the phosphorus component
Tris(2-methoxymethoxyphenyl)phosphine oxide: The residue obtained
after the distillation of (Z)-4-methyl-1-phenyl-1,3-pentadiene (9c; see
Section 2) was dissolved in ethyl acetate (250 mL) and filtered through a
short column of neutral alumina (40 mL). Evaporation of the solvent and
recrystallization from diethyl ether/pentanes (1:1) afforded colorless
[12] D. E. Bissing, J. Org. Chem. 1965, 30, 1296 ± 1298.
[13] W. E. Wadsworth, Org. React. 1977, 25, 73 ± 253.
[14] A. J. Gushurst, W. L. Jorgensen, J. Org. Chem. 1988, 53, 3397 ± 3408.
[15] G. Schmid, T. Fukuyama, K. Akasuka, Y. Kishi, J. Am. Chem. Soc.
1979, 101, 259 ± 260.
[16] G. Etemad-Maghadam, J. Seyden-Penne, Tetrahedron 1984, 40, 5153 ±
5166.
[17] W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405 ± 4408.
[18] A. Bernardi, S. Cardani, C. Scolastico, R. Villa, Tetrahedron 1988, 44,
491 ± 502.
1
granular crystals; m.p. 128 ± 1298C; 9.3 g (81%); H NMR: d ˆ 7.62 (ddd,
J ˆ 14.7, 7.6, 1.6 Hz, 3H), 7.43 (t, J ˆ 8.0 Hz, 3H), 7.13 (dd, J ˆ 8.3, 5.3 Hz,
3H), 7.01 (tdd, J ˆ 7.3, 2.2, 0.7 Hz, 3H), 4.96 (s, 6H), 3.02 (s, 9H); 13C NMR:
d ˆ 159.0 (s, 3C), 134.7 (d, J ˆ 9.6 Hz, 3C), 133.2 (s, 3C), 121.5 (d, J ˆ
110 Hz, 3C), 121.2 (d, J ˆ 12.9 Hz, 3C), 114.1 (d, J ˆ 6.4 Hz, 3C), 93.8 (s,
3C), 55.7 (s, 3C); 31P NMR: d ˆ 25.9; C24H27O7P (458.44): calcd C 62.88, H
5.94; found C 62.90, H 5.87.
[19] S. E. Denmark, J. A. Sternberg, J. Am. Chem. Soc. 1986, 108, 8277 ±
8281.
Tris(2-hydroxyphenyl)phosphine oxide: Hydrochloric acid (6m, 25 mL)
was added to a solution of tris(2-methoxymethoxyphenyl)phosphine oxide
(11.5 g, 25 mmol) in tetrahydrofuran (100 mL). After 10 min of reflux, the
mixture was cooled to 258C and the organic layer was separated. The
aqueous phase was extracted with ethyl acetate (4 Â 20 mL); the combined
organic layers were dried with anhydrous sodium sulfate. Removal of the
solvents and sublimation gave the product as colorless granular crystals;
m.p. 206 ± 2088C (ref. [67]: m.p. 214.5 ± 2168C); 6.6 g (81%); 1H NMR: d ˆ
9.4 (br, 3H), 7.46 (dd, J ˆ 8.2, 7.1 Hz, 3H), 7.0 (m, 6H), 6.90 (tdd, J ˆ 7.2, 3.0,
1.0 Hz, 3H); 13C NMR: d ˆ 162.2 (s, 3C), 135.5 (s, 3C), 131.8 (d, J ˆ
11.2 Hz, 3C), 119.9 (d, J ˆ 12.9 Hz, 3C), 118.9 (d, J ˆ 6.4 Hz, 3C), 111.6
(d, J ˆ 107 Hz, 3C); 31P NMR: d ˆ 52.3; C18H15O4P (326.29): calcd C 66.26,
H 4.63; found C 65.92, H 4.54.
[20] M. J. Hensel, P. L. Fuchs, Synth. Commun. 1986, 16, 1285 ± 1295.
[21] G. B. Hammond, M. B. Cox, D. F. Wiemer, J. Org. Chem. 1990, 55,
128 ± 132.
[22] Stereochemically unselective Horner reactions employing bis(2,2,2-
trifluoroethyl)(methoxycarbonylmethyl) phosphonates: P. L. Lopez-
Tudanca, K. Jones, P. Brownbridge, J. Chem. Soc. Perkin Trans. 1 1992,
533 ± 534.
[23] Z-Selective Horner reactions employing dimethyl or diethyl 1-
(methoxycarbonyl)ethyl phosphonates: G. Schmid, T. Fukuyama, K.
Akasaka, Y. Kishi, J. Am. Chem. Soc. 1979, 101, 259 ± 260; W. C. Still,
K. R. Shaw, Tetrahedron Lett. 1981, 22, 3725 ± 3728; W. Oppolzer, J. I.
Grayson, H. Wegmann, M. Urrea, Tetrahedron 1983, 39, 3695 ± 3705.
[24] J. M. J. Tronchet, B. Gentile, Helv. Chim. Acta 1979, 62, 2091 ± 2098;
H. O. House, V. K. Jones, G. A. Frank, J. Org. Chem. 1964, 29, 3327 ±
3333.
Tris(2-methoxymethoxyphenyl)phosphane: A freshly prepared solution of
aluminum hydride[68] (25 mmol) in tetrahydrofuran (50 mL) was added to a
solution of tris(2-methoxymethoxyphenyl)phosphine oxide (11.5 g,
[25] N. Minami, S. S. Ko, Y. Kishi, J. Am. Chem. Soc. 1982, 104, 1109 ± 1111.
Chem. Eur. J. 2000, 6, No. 3
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425

M. Schlosser et al.
FULL PAPER
[26] T. Katsuki, A. W. M. Lee, P. Ma, V. S. Martin, S. Masamune, K. B.
Sharpless, D. Tuddenham, F. J. Walker, J. Org. Chem. 1982, 47, 1373 ±
1378.
[27] J. Mulzer, M. Kappert, Angew. Chem. 1983, 95, 60; Angew. Chem. Int.
Ed. Engl. 1983, 22, 63 ± 64.
[28] F. Tabusa, T. Yamada, K. Suzuki, T. Mukaiyama, Chem. Lett. 1984,
405 ± 408.
[29] S. Valverde, M. Martin-Lomas, B. Herradon, S. Garcia-Ochoa,
Tetrahedron 1987, 43, 1895 ± 1901.
[30] C. Rüchardt, P. Panse, S. Eichler, Chem. Ber. 1967, 100, 1144 ± 1164.
[31] K. Ando, Tetrahedron Lett. 1995, 36, 4105 ± 4108; J. Org. Chem. 1997,
62, 1934 ± 1939.
[32] K. Ando, J. Org. Chem. 1998, 63, 8411 ± 8416.
[33] A. I. Meyers, K. Tomioka, D. M. Roland, D. Comins, Tetrahedron Lett.
1978, 19, 1375 ± 1378.
[49] F. Näf, R. Decorzant, W. Thommen, B. Willhalm, G. Ohloff, Helv.
Chim. Acta 1975, 58, 1016 ± 1037.
[50] L. Jaenicke, K. Seferiadis, Chem. Ber. 1975, 108, 225 ± 232.
[51] Early examples of vinylogous (ethenylogous) and doubly vinylogous
carbonyl attack at allylic ylides: G. Büchi, H. Wüest, Helv. Chim. Acta
1971, 54, 1767 ± 1776; F. Bohlmann, C. Zdero, Chem. Ber. 1973, 106,
3779 ± 3787; G. Büchi, M. Pawlak, J. Org. Chem. 1975, 40, 100 ± 105;
W. G. Dauben, D. J. Hart, J. Ipaktschi, A. P. Kozikowski, Tetrahedron
Lett. 1973, 44, 4425 ± 4428; S. F. Martin, S. R. Desai, J. Org. Chem.
1978, 43, 4673 ± 4675; for a recent example see: D. F. Schneider, A. C.
Venter, Synth. Commun. 1999, 29, 1303 ± 1315.
[52] S. Griffin, L. Heath, P. Wyatt, Tetrahedron Lett. 1998, 39, 4405 ± 4406;
see also A. Bootle-Wilbraham, S. Head, J. Longstaff, P. Wyatt,
Tetrahedron Lett. 1999, 40, 5267 ± 5270.
[53] O. Desponds, L. Franzini, M. Schlosser, Synthesis 1997, 150 ± 152; M.
Schlosser, J. Porwisiak, F. Mongin, Tetrahedron 1998, 54, 895 ± 900; Q.
Wang, H.-x. Wei, M. Schlosser, Eur. J. Org. Chem. 1999, in press.
[54] W. C. Young, J. F. Lane, J. Am. Chem. Soc. 1937, 59, 2051 ± 2056.
[55] J. Beger, E. Meerbote, J. Prakt. Chem. 1984, 326, 12 ± 22.
[56] Y. R. Naves, Bull. Soc. Chim. Fr. 1967, 3152 ± 3154.
[34] A. I. Meyers, R. K. Smith, C. E. Whitten, J. Org. Chem. 1979, 44,
2250 ± 2256.
[35] R. W. Dugger, C. H. Heathcock, Synth. Commun. 1980, 10, 509 ± 515.
[36] D. K. Hutchinson, P. L. Fuchs, J. Am. Chem. Soc. 1987, 109, 4755 ±
4756.
[37] M. Schlosser, V. Ladenberger, Chem. Ber. 1971, 104, 2873 ± 2884.
[38] E. Vedejs, H. W. Fang, J. Org. Chem. 1984, 49, 210 ± 212.
[39] R. Tamura, K. Saegusa, M. Kakihana, D. Oda, J. Org. Chem. 1988, 53,
2723 ± 2728; see also: R. Tamura, M. Kato, K. Saegusa, M. Kakihana,
D. Oda, J. Org. Chem. 1987, 52, 4121 ± 4124.
[57] E. A. Braude, E. S. Stern, J. Chem. Soc. 1947, 1087 ± 1096.
[58] O. Grummitt, F. J. Christoph, J. Am. Chem. Soc. 1949, 71, 4157.
[59] J. M. Landesberg, L. Katz, J. Organomet. Chem. 1972, 35, 327 ± 336.
[60] F. Auclair, A. Kergomard, H. Veschambre, Bull. Soc. Chim. Fr. 1976,
142 ± 144.
[40] R.-q. Liu, M. Schlosser, Synlett 1996, 1195 ± 1196.
[41] R.-q. Liu, M. Schlosser, Synlett 1996, 1197 ± 1198.
[42] H. Düttmann, P. Weyerstahl, Chem. Ber. 1979, 112, 3480 ± 3485.
[43] M. Schlosser, B. Schaub, J. Am. Chem. Soc. 1982, 104, 5821 ± 5823.
[44] B. Schaub, S. Jeganathan, M. Schlosser, Chimia 1986, 40, 246 ± 247.
[45] S. Jeganathan, M. Tsukamoto, M. Schlosser, Synthesis 1990, 109 ± 111.
[46] M. Tsukamoto, M. Schlosser, Synlett 1990, 605 ± 608.
[47] X.-p. Zhang, M. Schlosser, Tetrahedron Lett. 1993, 34, 1925 ± 1928.
[48] H. J. Bestmann, J. Süû, O. Vostrowsky, Liebigs Ann. Chem. 1981,
2117 ± 2138; D. L. Boger, O. Hüter, K. Mbiya, M.-s. Zhang, J. Am.
Chem. Soc. 1995, 117, 11839 ± 11849; I. Fleming, G. R. Jones, N. D.
Kindon, Y. Landais, C. P. Leslie, I. T. Morgan, S. Peukert, A. K.
Sarkar, J. Chem. Soc. Perkin Trans. 1 1996, 1171 ± 1196.
[61] E. Vogel, G. Caravatti, P. Franck, P. Aristoff, C. Moody, A.-M. Becker,
D. Felix, A. Eschenmoser, Chem. Lett. 1987, 219 ± 222.
[62] E. W. Duck, J. M. Locke, S. R. Wallis, J. Chem. Soc. (C) 1970, 2000 ±
2007.
[63] L. Audier, Ann. Chim. 1957, 105 ± 137.
[64] T. Hayashi, A. Sakurai, T. Oishi, Chem. Lett. 1977, 1483 ± 1486.
[65] W. S. Emerson, J. Org. Chem. 1945, 10, 464 ± 469.
[66] K. Alder, K. Hermbach, E. Kühle, Chem. Ber. 1953, 86, 1364 ± 1371.
[67] J. Kennedy, E. S. Lane, J. L. Willans, J. Chem. Soc. 1956, 4670 ± 4675;
O. Neunhoeffer, L. Lamza, Chem. Ber. 1961, 94, 2514 ± 2518.
[68] H. C. Brown, N. M. Yoon, J. Am. Chem. Soc. 1966, 88, 1464 ± 1472.
Received: June 7, 1999 [F1837]
426
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