New phosphonate reagents for aldehyde homologation

Article abstract of DOI:10.1080/00397910701569114

New phosphonate reagents were developed for the two-carbon homologation of aldehydes to unbranched or methyl-branched unsaturated aldehydes. The phosphonate reagents, diethyl methylformylphosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with aliphatic, α,β-unsaturated and aromatic aldehydes. Isolated yields for the condensation step ranged from 77% to 89%, and yields for the deprotection step ranged from 81% to 96%. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701569114

This article was downloaded by: [University of Illinois Chicago]
On: 27 November 2014, At: 13:57
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
New Phosphonate Reagents for Aldehyde
Homologation
Richard J. Petroski a
a United States Department of Agriculture , Agricultural Research Service,
National Center for Agricultural Utilization Research, Crop Bioprotection
Research Unit , Peoria, Illinois, USA
Published online: 19 Oct 2007.
To cite this article: Richard J. Petroski (2007) New Phosphonate Reagents for Aldehyde Homologation,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:21, 3841-3854, DOI: 10.1080/00397910701569114
To link to this article: http://dx.doi.org/10.1080/00397910701569114
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 37: 3841–3854, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701569114
New Phosphonate Reagents for Aldehyde
Homologation
Richard J. Petroski
United States Department of Agriculture, Agricultural Research Service,
National Center for Agricultural Utilization Research, Crop
Bioprotection Research Unit, Peoria, Illinois, USA
Abstract: New phosphonate reagents were developed for the two-carbon homologa-
tion of aldehydes to unbranched or methyl-branched unsaturated aldehydes. The phos-
phonate reagents, diethyl methylformylphosphonate dimethylhydrazone and diethyl
ethylformyl-2-phosphonate dimethylhydrazone, contained
a protected aldehyde
group instead of the usual ester group. A homologation cycle entailed condensation
of the reagent with the starting aldehyde, followed by removal of the dimethylhydra-
zone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This
robust two-step process worked with aliphatic, a,b-unsaturated and aromatic
aldehydes. Isolated yields for the condensation step ranged from 77% to 89%, and
yields for the deprotection step ranged from 81% to 96%.
Keywords: aldehyde homologation, diethyl ethylformyl-2-phosphonate dimethyl-
hydrazone, diethyl methylformylphosphonate dimethylhydrazone
INTRODUCTION
A recurring theme in the synthesis of various polyketide natural products and
other compounds is two-carbon homologation of aldehydes to a,b-unsaturated
aldehydes and a-methyl-a,b-unsaturated aldehydes. A typical approach based
on the Horner–Wadsworth–Emmons condensation[1] uses a phosphonate
Received in USA March 30, 2007
Address correspondence to Richard J. Petroski, United States Department of Agri-
culture, Agricultural Research Service, National Center for Agricultural Utilization
Research, Crop Bioprotection Research Unit, 1815 N. University Street, Peoria,
Illinois 61604, USA. E-mail: richard.petroski@ars.usda.gov
3841

3842
R. J. Petroski
ester, such as triethyl phosphonoacetate or triethyl-2-phosphonopropionate,
and involves three synthetic steps: The phosphonate condensation step
extends the chain by two carbons while introducing an (E) double bond, an
a-alkyl branch (size depending on the choice of phosphonate reagent), and
a terminal ester group. The ester is then reduced to an a,b-unsaturated
alcohol, and the alcohol is partially oxidized to the desired a,b-unsaturated
aldehyde. One way to shorten this scheme would be to use a homologating
reagent that keeps the oxidation state of an aldehyde throughout.
A variety of options were considered. Aldehyde Wittig reagents, such as
a-formylethylidenetriphenylphosphorane, are known,[2,3] but in my hands the
reagent was not reactive toward a,b-branched unsaturated aldehydes, such as
(2E)-2-methyl-2-butenal (Petroski, unpublished results). Phosphonate anions
are generally more reactive toward aldehydes than the analogous phospor-
anes.[4] Aldehyde phosphonates (where the ester group is replaced by an
aldehyde) can be readily prepared,[5] but using them directly in
Wittig–Horner reactions is not practicable because of self-condensation.
Reactions using aldehyde phosphonates protected as imines and acetals
have been reported, but these reagents also have problems with side
reactions, insufficient reactivity, and lability of products.[6] The silylaldimines
are the functional equivalents of protected aldehyde phosphonates and have
been used in Wittig–Horner-like reactions;[7,8] however, reaction conditions
to form and use silylaldimines are not operationally convenient,[8] and I
chose to further explore phosphonate chemistry.
Protection of carbonyl compounds as dimethylhydrazones is a common
practice, and the incorporation and removal of this group have been studied
extensively.[9–11] However, to my knowledge, the use of aldehyde phospho-
nates protected as dimethylhydrazones in Horner–Wadsworth–Emmons
reactions had not been exploited previously.
In this article, I report the preparation and use of diethyl methylformyl-
phosphonate dimethylhydrazone (1) and diethyl 1-ethylformyl-2-phosphonate
dimethylhydrazone (2) for the two-carbon homologation of aldehydes to
a,b-unsaturated aldehydes and a-methyl-a,b-unsaturated aldehydes after
deprotection. The new reagents were tested with alkyl, a,b-unsaturated, and
aromatic aldehydes (Fig. 1).
RESULTS AND DISCUSSION
The new phosphonate reagents, 1 and 2, were prepared without difficulty, were
stable enough to be distilled, and readily entered condensation reactions with
aliphatic, a,b-unsaturated and aromatic aldehydes. Subsequent removal of the
dimethylhydrazone protective group could be easily accomplished, even for
delicate product aldehydes (Fig. 1). Using these reagents led to a two-step
aldehyde homologation cycle (condensation and deprotection) instead of the

New Phosphonate Reagents
3843
Figure 1. Synthetic pathways and products. Reaction conditions: (a) phosphonate 1,
LiN(iPr)2, THF, 258C, 3 to 5 h; (b) phosphonate 2, LiN(iPr)2, THF, 258C, 20 h; (c) 1 M
HCl and pet. ether, 258C, 5 to 48 h, time varies with compound. Preparation of phos-
phonate 1: (1a) diethyl methylphosphonate, THF, BuLi; (1b) Me2NCHO; (1c) 3 M
HCl, 1a–c in one pot; (2) H2N-NMe2, MgSO4, CH2Cl2, 258C, 48 h. Preparation of
phosphonate 2: (1a) diethyl ethylphosphonate, THF, BuLi; (1b) Me2NCHO; (1c)
3 M HCl, 1a–c in one pot; (2) H2N-NMe2, MgSO4, CH2Cl2, 258C, 48 h.
previous three-step cycle. Overall yields for the two-step sequence ranged
from 71% to 84%.
Reagents 1 and 2 were synthesized from commercially available diethyl
methylphosphonate and diethyl ethylphosphonate. Diethyl alkylphosphonate
starting materials were formulated to prepare diethyl methylformylpho-
sphonate and diethyl ethylformyl-2-phosphonate[5] and then the aldehyde

3844
R. J. Petroski
functional group was protected as the dimethylhydrazone derivative.[10] The
new method requires the phosphonate reagents to be synthesized, whereas
those for the original method are available commercially. Nevertheless,
large batches of the new reagents can be prepared and stored, and these
stocks could subsequently serve for syntheses of a variety of final products.
Diethyl methylformylphosphonate can also be named (2-oxo-ethyl)-
phosphonic acid diethyl ester, and diethyl ethylformyl-2-phosphonate can
also be named (1-methyl-2-oxo-ethyl)-phosphonic acid diethyl ester.
Diethyl methylformylphosphonate dimethylhydrazone can also be named
[2-(dimethyl-hydrazino)-ethyl]- phosphonic acid diethyl ester, and diethyl
ethylformyl-2-phosphonate dimethylhydrazone can also be named
[2-(dimethyl-hydrazino)-1-methyl-ethyl]-phosphonic acid diethyl ester. I
chose to use the simpler, and more intuitive, names in this paper.
Both 1 and 2 were readily converted to their anions with the lithium
diisopropylamide (LDA) base and reacted smoothly with aldehydes, added
in excess, to give unbranched or methyl-branched, unsaturated aldehyde
dimethylhydrazones with chains having two additional carbons (Fig. 1).
Yields for the condensation step ranged from 77% to 89%.
Deprotection of unsaturated aldehyde dimethylhydrazones was accom-
plished in 81%–96% yield, using a biphasic mixture of 1 M HCl and
petroleum ether.[11] In the deprotection reaction, the dimethylhydrazone is
initially converted to a water-soluble hydrochloride salt, and the free
aldehyde then forms under the acidic conditions. Successful deprotection
requires immediate migration of the liberated, but sometimes labile,
aldehyde from the aqueous phase to the neutral petroleum ether phase. This
procedure gave a favorable (9.5:1 to 170:1) ratio of 2E to 2Z products. In
the absence of petroleum ether, dimethylhydrazones 4a and 4c gave a
complex mixture of reaction products.
The major isomer configuration, at the a,b-double bond of compounds
3a, 3b, 4a, 4b, 5a, and 5b, was readily determined to be E by the coupling
constant of J2–3 ¼ 15.1 to J2–3 ¼ 16.1 Hz. The major isomer configuration
of all trisubstituted double bonds of compounds 3c, 3d, 4c, 4d, 5c, and 5d
was determined by nuclear Overhauser enhancement (nOe) NMR methods.
Irradiation at either H-1 or H-3 caused a nuclear Overhauser enhancement
of 2.1 to 4.3% at H-1 or H-3 for compounds 3c, 3d, 4c, 4d, 5c, and 5d but
only an nOe of 0 to 0.2% was observed for the methyl group protons for
any of the compounds. Irradiation of the methyl group protons caused a
nOe of just 0 to 0.5% for either H-1 or H-3. The data support the assignment
of 2E configuration for compounds 3c, 3d, 4c, 4d, 5c, and 5d because the H-1
and H-3 protons are closer to each other than to the protons of the methyl
group, attached to C-2.
This more concise aldehyde homologation chemistry could be applied to
the practical synthesis of a variety of natural products, pharmaceuticals, and
other compounds. The starting materials are sufficiently inexpensive and the
reactions are sufficiently robust to make use of this two-step process

New Phosphonate Reagents
3845
commercially viable. Furthermore, the new method eliminates the use and
disposal of some metal-containing reagents (reducing agents such as lithium
aluminum hydride and oxidants such as manganese dioxide). An ethyl-
branched phosphonate, diethyl 1-propylformyl-2-phosphonate dimethylhy-
drazone, and its use in the practical synthesis of a tetraene-hydrocarbon
insect pheromone, will be a subject of a future article.
EXPERIMENTAL
Chemicals and General Methods
Diethyl methylphosphonate and diethylethylphosphonate were purchased
from Alfa Aesar (Ward Hill, MA). Diethyl ethylphosphonate can also be
prepared in 98% yield by refluxing a mixture of triethyl phosphite and ethyl
iodide for 3 h.[12] THF was purified by distillation from sodium benzo-
phenone ketyl. Lithium diisopropylamide (LDA) was purchased from the
Aldrich Chemical Co (Milwaukee, WI) as a 2 M solution in a mixture of
heptane/THF/ethylbenzene. Other organic reagents were obtained from
Aldrich and were used without further purification. Nonaqueous reactions
were performed under an atmosphere of dry argon in oven-dried glassware.
Removal of solvent was accomplished by rotary evaporation at water
aspirator pressure.
Analysis of Reaction Products
Progress of synthetic reactions was monitored by gas chromatography (GC).
All reaction products were identified by GC/MS and the structures were
additionally verified by NMR. The proportion of unwanted 2Z-isomer
product was identified by shorter GC retention time and nearly identical
mass spectra, compared to the 2E-isomer.[13] Yields were corrected for
purity. Both 2E and 2Z isomers were considered to be the product;
however, the 2E:2Z isomer ratios are given.
The Hewlett-Packard (HP) 5890 Series II gas chromatograph was
equipped with flame ionization detector and split/splitless inlet and was inter-
faced to an HP ChemStation data system. The column was a DB-5 capillary
(30 m ꢀ 0.25 mm, 0.25-mm film thickness, J&W Scientific, Folsom, CA).
Carrier gas was He. The oven temperature was programmed from 50 to
2808C at 108C/min, and the detector temperature was 2808C. The inlet temp-
erature was 1208C, and 1.0-mL sample injections were made in splitless mode.
Considerable degradation of unsaturated aldehyde dimethylhydrazones was
observed during GC runs with higher inlet temperatures, especially for
compounds 4a and 4c.

3846
R. J. Petroski
Electron impact mass spectra (70 eV) were obtained with an HP 5973
MSD instrument, interfaced to an HP 6890 GC, equipped with a splitless
inlet. Several columns were used but gave comparable results to that used for
GC. The oven temperature was programmed from 50 to 2508C at 108C/min;
the inlet temperature was 1208C, and the transfer line temperature was 2508C.
1H NMR, 13C NMR, and 2D NMR spectra were collected on a Bruker
(Bellerica, MA) Avance 500 spectrometer using a 5-mm inverse broadband
probe. Samples were dissolved in either CDCl3 or C6D6 (where indicated)
and all spectra were acquired at 3008K (1H and 2-D homonuclear one-bond
J coupling correlation spectroscopy (COSY) spectra were acquired at
500 MHz whereas 13C and distortionless enhancement by polarization
transfer (DEPT) apectra were acquired at 125 MHz.). Trisubstituted double-
bond “E” or “Z” assignments were based on 1D pulse magnetic field
gradient unclear Overhauser enhancement (PFG-NOE) experiments and 2D
pulse magnetic field gradient unclear Overhauser enhancement spectroscopy
(PFG-NOESY) experiments. Chemical shifts are reported as parts per million
from tetramethylsilane with an absolute frequency J ¼ 500.11 MHz.
Coupling constants (J) are in Hertz. Assignments were made with the help of
1H- and 13C-Predictive software[14] and by analogy to known compounds.
Methyl branches are reported by the point of attachment to the carbon chain
(e.g., CH3 at C-2). Although compounds 4b and 4d are known, spectral data
are given because MS and NMR data are very difficult to find in the older
chemical literature.
Diethyl Methylformylphosphonate Dimethylhydrazone (1)
A solution of n-butyllithium (2.5 M, 25 mL, 0.063 mol, slight excess) was
added to dry THF (80 mL), and the mixture was cooled in an argon atmosphere
to dry ice–ethanol bath temperature (approx 2788C). Diethyl methylphospho-
nate (9.13 g, 8.8 mL, 0.06 mol) was added dropwise, and the mixture was stirred
for an additional hour before dry dimethylformamide (DMF, distilled from
CaH2, 4.8 mL, 0.066 mol) was added. After warming to 208C, ice-cold 3 M
aqueous HCl (90 mL) was added, and the mixture was stirred for 5 min.
A fine white precipitate formed initially, and then the solution cleared and
separated into two phases (liberation of the free phosphonate aldehyde). The
phases were separated, and the organic phase was washed with 10 mL of
alkaline brine solution (0.5% NaHCO3 in saturated aqueous NaCl), dried over
anhydrous MgSO4, and filtered. The acidic aqueous phase was repeatedly
extracted with CH2Cl2 (5 ꢀ 50 mL), and the combined CH2Cl2 extracts were
washed with alkaline brine solution (2 ꢀ 10 mL). The alkaline brine washes
were combined and extracted again with CH2Cl2 (4 ꢀ 15 mL). All CH2Cl2
extracts were combined, dried over anhydrous MgSO4, and filtered. Solvent
was removed from the dried organic phase and all dried CH2Cl2 extracts to
afford 9.8 g of crude diethyl methylformyl-2-phosphonate, which still
contained some DMF. Without further purification, the crude product was

New Phosphonate Reagents
3847
converted to the dimethylhydrazone (DMH) derivative by adding it to a mixture
of CH2Cl2 (200 mL) containing anhydrous MgSO4 (14.4 g, 0.12 mol), and then
N,N-dimethylhydrazine (4.7 g, 6 mL, 0.08 mol) was added in one portion. The
mixture was stirred (48 h) until analysis by GC showed complete protection of
the aldehyde as the DMH derivative. Filtration, removal of solvent, and
Kugelrohr distillation (oven temperature 448C, 0.02 torr) afforded 7.1 g of 1
(purity 93%, yield corrected for purity 50%). MS (EI) m/z (%) 222 (Mþ, 32),
180 (9), 152 (91), 125 (100), 122 (74), 108 (27), 97 (37), 85 (85), 71 (15), 58
1
(8), 44 (91). EI-HRMS C8H19N2O3P calcd. for 222.1133 (obs. 222.1133). H
NMR d1.30 (6H, t, J ¼ 7.0, CH3-CH2-O), 2.77 (6H, s, N-CH3), 2.81 (1H, dt,
J1–2 ¼ 5.8, H-2), 4.09, (4H, q, J ¼ 7.0, CH3-CH2-O), 6.47 (1H, br d, J1–
¼ 5.8, H-1). 13C NMR d 16.4 (CH3-CH2-O), 31.3 (C-2), 42.9 (N-CH3), 61.9
2
(CH3-CH2-O), 126.1 (C-1).
Diethyl Ethylformyl-2-phosphonate Dimethylhydrazone (2)
A solution of n-butyllithium (2.5 M, 85 mL, 0.213 mol, slight excess) was
added to dry THF (250 mL), and the mixture was cooled in an argon atmos-
phere to dry ice–ethanol bath temperature (approx. 788C). Diethyl ethylpho-
sphonate (33.2 g, 32.4 mL, 0.20 mol) was added dropwise, and the mixture
was stirred for an additional hour before dry DMF (20 mL, 0.26 mol) was
added. After warming to 208C, ice-cold 3 M aqueous HCl (300 mL) was
added, and the mixture was stirred 5 min. A fine white precipitate formed
initially, and then the solution cleared and separated into two phases (liber-
ation of the free phosphonate aldehyde). The phases were separated, and the
organic phase was washed with 30 mL of alkaline brine solution (0.5%
NaHCO3 in saturated aqueous NaCl), dried over anhydrous MgSO4, and
filtered. The acidic aqueous phase was repeatedly extracted with CH2Cl2
(5 ꢀ 150 mL), and the combined CH2Cl2 extracts were washed with 30 mL
of alkaline brine solution. The alkaline brine washes were combined and
extracted again with CH2Cl2 (4 ꢀ 15 mL). All CH2Cl2 extracts were
combined, dried over anhydrous MgSO4, and filtered. Solvent was removed
from the dried organic phase and all dried CH2Cl2 extracts to afford 44 g of
crude diethyl ethylformyl-2-phosphonate, which still contained some DMF.
Without further purification, the crude product was converted to the dimethyl-
hydrazone (DMH) derivative by adding it to a mixture of CH2Cl2 (600 mL)
containing anhydrous MgSO4 (48 g, 0.4 mol), and then N,N-dimethylhydra-
zine (15.6 g, 20 mL, 0.26 mol) was added in one portion. The mixture was
stirred (48 h) until analysis by GC showed complete protection of the
aldehyde as the DMH derivative. Filtration, removal of solvent, and
Kugelrohr distillation (oven temperature 508C, 0.04 torr) afforded 47.6 g of
3 (purity 98%, yield corrected for purity 97%). Isolated yields of more than
95% were routinely obtained. MS (EI) m/z (%) 236 (Mþ, 34), 194 (8), 166
(82), 136 (42), 122 (10), 111 (12), 99 (100), 53 (12), 81 (12), 72 (11), 56
(12), 44 (36). EI-HRMS C9H21N2O3P calcd. for 236.1290 (obs. 236.1293).

3848
R. J. Petroski
1H NMR d 1.19 and 1.20 (6H, overlapping t, J ¼ 7.0, CH3-CH2-O), 1.26 (3H,
d, J2–3 ¼ 7.3, H-3), 2.76 (1H, dt, J1–2 ¼ 4.1 and J2–3 ¼ 7.3, H-2), 2.66 (6H,
s, N-CH3), 3.99 and 4.00 (4H, overlapping q, J ¼ 7.0, CH3-CH2-O), 6.38 (1H,
br d, J1–2 ¼ 4.1, H-1). 13C NMR d 12.7 (C-3), 16.4 (CH3-CH2-O), 36.0 and
37.1 (C-2, isomers), 43.1 (N-CH3), 62.0 (CH3-CH2-O), 132.6 (C-1).
(2E)-N,N-Dimethyl-N0-(dec-2-enylidene)-hydrazine (3a)
A commercial 2.0 M solution of LDA (5.2 mL, 10.4 mmol, slight excess) was
added dropwise (reaction exothermic) to a 250-mL round-bottomed flask con-
taining dry THF (25 mL), 1 (2.22 g, containing 2.06 g of 1, 9.3 mmol), and a
few milligrams of ethyl(triphenyl)phosphonium bromide, as an indicator, and
the mixture was stirred in an argon atmosphere at rt for 1.5 h to ensure
complete formation of the phosphonate ylide. A persistent red color
developed in the solution when sufficient base was added to convert the phos-
phonate to its anion. Then, n-octanal (1.67 g, 13 mmol) was added dropwise;
final color was yellow-orange. The mixture was stirred at rt for 5 h. Consump-
tion of the phosphonate 1 was monitored by GC. Water (6 mL) was added to
quench the reaction (excess water should be avoided because it leads to pro-
blematic emulsions during subsequent extraction steps). The solvent was
removed by rotary evaporation to give an oily residue, which was extracted
with ethyl acetate (5 ꢀ 25 mL). The combined extracts were washed with
saturated aqueous NaCl solution (15 mL), dried over anhydrous Na2SO4,
and filtered. Removal of solvent left a yellow oil. Kugelrohr distillation
(oven temperature 598C, 0.05 torr) afforded 1.80 g of 3a (89% purity by
GC, yield corrected for purity 88%). By GC and GC-MS, the 2E/2Z isomer
ratio was 8.5 to 1. MS (EI) m/z (%) 196 (Mþ, 72), 181 (8), 167 (2), 152
(19), 140 (7), 125 (14), 111 (100), 82 (40), 59 (21), 44 (32), 42 (19).
1
EI-HRMS C12H24N2 calcd. for 196.1939 (obs. 196.1940). H NMR d 0.89
(3H, t, J9–10 ¼ 6.9, H-10), 1.27–1.30 (8H, m, H-6 to H-9), 1.42 (2H, m,
H-5), 2.15 (2H, m, J3–4 ¼ 7.8, H-4), 2.84 (6H, s, N-CH3), 5.87 (1H, dd,
J3–4 ¼ 7.8 and J2–3 ¼ 15.5, 55CH, H-3), 6.20 (1H, dd, J1–2 ¼ 9.1 and
J2–3 ¼ 15.5, 55CH, H-2), 7.11 (1H, d, J1–2 ¼ 9.1, 55CH, H-1). 13C NMR
d13.3 (C-10), 22.6 (C-9), 29.0 (C-5, C-6, and C-7), 31.7 (C-8), 32.6 (C-4),
43.0 (N-CH3), 128.6 (C-2), 136.4 (C-3), 137.6 (C-1).
(2E)-2-Decenal (3b)
Deprotection was initiated by stirring 3a (1.10 g, containing 0.98 g 3a,
5.0 mmol) with 1 M HCl (50 mL) at room temperature for 5 min (3a
dissolves as the hydrochloride salt forms), and then petroleum ether (bp 35
to 608C, 50 mL) was added and stirring continued. After 4 h, the phases
were separated, and the aqueous phase was returned to the reaction vessel.
Petroleum ether (30 mL) was added, and the mixture was stirred at rt for an
additional 1 h before the phases were separated. The combined petroleum

New Phosphonate Reagents
3849
ether phases were washed with alkaline brine solution (2 ꢀ 10 mL), and the
brine phase was back-extracted once with petroleum ether (20 mL). The
combined organic phases were dried and filtered, and removal of solvent
afforded 0.75 g of the free aldehyde 3b. Purity by GC was 92%, and yield
corrected for purity was 90%. The 2E:2Z isomer ratio was 25 to 1. The MS
and NMR spectral data were consistent with the reference spectral data
from previous work.[8]
(2E)-N,N-Dimethyl-N0-(2-methyl-dec-2-enylidene)-hydrazine (3c)
Compound 3c was prepared in a way similar to compound 3a. The phosphonate
anion was prepared from 2 (2.36 g, containing 2.31 g of 2, 9.8 mmol) in THF
(25 mL) by treatment with LDA (2.0 M, 5.2 mL, 10.4 mmol, slight excess),
and n-octanal (1.92 g, 15 mmol) was subsequently added. The mixture was
stirred at rt for 20 h. Water (3 mL) was added to quench the reaction, and the
reaction was worked up as before. Kugelrohr distillation (oven temperature
698C, 0.1 torr) afforded 2.04 g of 3c (90% purity by GC, yield corrected for
purity 89%). By GC and GC-MS, the 2E/2Z isomer ratio was 8.2 to 1. MS
(EI) m/z (%) 210 (Mþ, 68), 195 (24), 180 (3), 166 (82), 125 (100), 111 (13),
96 (29), 82 (37), 59 (18), 44 (31), 42 (15). EI-HRMS C13H26N2 calcd. for
210.2096 (obs. 210.2093). 1H NMR d 0.90 (3H, t, J9–10 ¼ 7.0, H-10),
1.28–1.31 (8H, m, H-6 to H-9), 1.41 (2H, m, H-5), 1.84 (3H, s, CH3 attached
to C-2), 2.20 (2H, m, H-4), 2.83 (6H, s, N-CH3), 5.61 (1H, dd, J3–4 ¼ 6.9,
55CH, H-3), 7.15 (1H, s, 55CH, H-1). 13C NMR d 11.6 (CH3 attached to
C-2), 14.1 (C-10), 22.6 (C-9), 28.1 (C-4), 29.3 (C-6 and C-7), 29.9 (C-5),
31.9 (C-8), 43.0 (N-CH3), 132.4 (C-2), 134.2 (C-3), 141.2 (C-1).
(2E)-2-Methyl-2-decenal (3d)
Deprotection procedure was similar to that used for 3b. A solution containing
3c (1.15 g, containing 1.04 g of 3c, 5.0 mmol) and 1 M HCl (60 mL), to which
petroleum ether (bp 35 to 608C, 60 mL) was added after 5 min, was stirred at
room temperature for 6 h. The phases were separated, and the aqueous phase
was returned to the reaction vessel. Petroleum ether (40 mL) was added, and
the mixture was stirred at rt for an additional 1 h before the phases were
separated. Workup of the reaction as for 3b resulted in 0.85 g of the free
aldehyde 3d (purity by GC showed 90%, yield corrected for purity 91%).
The 2E:2Z isomer ratio was 24 to 1. The MS and NMR spectral data were con-
sistent with the reference spectral data from previous work.[15]
(2E,4E)-N0-(Undeca-2,4-dienylidene)-N,N-dimethyl-hydrazine (4a)
Compound 4a was prepared in a way similar to compound 3a. The phospho-
nate anion was prepared from 1 (2.22 g, containing 2.06 g of 1, 9.3 mmol) in
THF (25 mL) by treatment with LDA (2.0 M, 5.2 mL, 10.4 mmol, slight

3850
R. J. Petroski
excess), and (2E)-2-nonenal (1.68 g, 12 mmol) was subsequently added. The
mixture was stirred at rt for 3 h. Water (6 mL) was added to quench the
reaction, and the reaction was worked up as before. Kugelrohr distillation
(oven temperature 708C, 0.05 torr) afforded 1.62 g of 4a (92% purity by
GC, yield corrected for purity 77%). By GC and GC-MS, the 2E/2Z isomer
ratio was 16 to 1. MS (EI) m/z (%) 208 (Mþ, 18), 137 (3), 123 (100), 108
(2), 94 (8), 80 (11), 67 (5), 44 (7), 42 (3). EI-HRMS C13H24N2 calcd. for
208.1939 (obs. 208.1944). 1H NMR d 0.90 (3H, t, J10–11 ¼ 7.2, H-11),
1.29–1.31 (6H, m, H-8 to H-10), 1.41 (2H, m, H-7), 2.12 (2H, m, J5–
¼ 7.2, H-6), 2.87 (6H, s, N-CH3), 5.75, (1H, dt, J5–6 ¼ 7.2 and J4–
6
¼ 15.0, 55CH, H-5), 6.13 (1H, dd, J3–4 ¼ 10.0 and J4–5 ¼ 15.0, 55CH,
5
H-4), 6.28 (1H, m, J3–4 ¼ 10.0 and J2–3 ¼ undeterminable in CDCl3,
55CH, H-3), 6.28 (1H, m, J1–2 ¼ 6.0 and J2–3 ¼ undeterminable in CDCl3,
1
55CH, H-2), 7.05 (1H, d, J1–2 ¼ 6.0, 55CH, H-1). H NMR in C6D6 d 0.98
(3H, t, J10–11 ¼ 7.8, H-11), 1.29–1.31 (6H, m, H-8 to H-10), 1.41 (2H, m,
H-7), 2.10 (2H, m, J5–6 ¼ 7.2, H-6), 2.63 (6H, s, N-CH3), 5.77 (1H, dt, J5–
¼ 7.2 and J4–5 ¼ 15.1, 55CH, H-5), 6.22 (1H, dd, J3–4 ¼ 10.4 and J4–
6
¼ 15.1, 55CH, H-4), 6.41 (1H, dd, J3–4 ¼ 10.4 and J2–3 ¼ 15.1, 55CH,
5
H-3), 6.72 (1H, dd, J1–2 ¼ 8.5 and J2–3 ¼ 15.1, 55CH, H-2), 7.14 (1H, d,
J1–2 ¼ 8.5, 55CH, H-1). 13C NMR d14.0 (C-11), 22.6 (C-10), 28.9 (C-8),
29.2 (C-7), 31.6 (C-9), 32.8 (C-6), 42.9 (N-CH3), 128.6 (C-2), 130.3 (C-4),
133.2 (C-3), 135.8 (C-5), 136.2 (C-1).
(2E,4E)-2,4-Undecadienal (4b)
Deprotection procedure was similar to that used for 3b. A solution containing
4a (1.16 g, containing 1.07 g of 4a, 5.1 mmol) and 1 M HCl (50 mL), to which
petroleum ether (bp 35 to 608C, 50 mL) was added after 5 min, was stirred at
room temperature for 24 h. The phases were separated, and the aqueous phase
was returned to the reaction vessel. Petroleum ether (40 mL) was added, and
the mixture was stirred at rt for an additional 1 h before the phases were
separated. Workup of the reaction as for 3b resulted in 0.81 g of the free
aldehyde 4b (purity by GC showed 93%, yield corrected for purity 89%).
The 2E:2Z isomer ratio was 9.5 to 1. MS (EI) m/z (%) 166 (Mþ, 6), 137
92), 123 (4), 109 (5), 95 (12), 81 (100), 67 (15), 55 (11), 43 (10), 41 (18).
1H NMR d 0.91 (3H, t, J10–11 ¼ 6.9, H-11), 1.30–1.32 (6H, m, H-8 to
H-10), 1.47 (2H, m, J6–7 ¼ 7.2, H-7), 2.24 (2H, dt, J5–6 ¼ 6.6 and
J6–7 ¼ 7.2, H-6), 6.09 (1H, dd, J1–2 ¼ 7.9 and J2–3 ¼ 15.1, 55CH, H-2),
5.79 (minor 2Z isomer, 1H, dd, J1–2 ¼ 7.9 and J2–3 ¼ 11.2, 55CH, H-2), 6.31
(1H, m, J5–6 ¼ 6.6 and J4–5 ¼ undeterminable in CDCl3, 55CH, H-5), 6.31
(1H, d, J3–4 ¼ 9.8 and J4–5 ¼ undeterminable in CDCl3, 55CH, H-4), 7.10
(major 2E isomer: 1H, dd, J3–4 ¼ 9.8 and J2–3 ¼ 15.1, 55CH, H-3), 6.93
(minor 2Z isomer, 1H, dd, J3–4 ¼ 9.8 and J2–3 ¼ 11.2, 55CH, H-3), 9.55 (1H,
d, J1–2 ¼ 7.9, O55CH, H-1), 10.19 (minor 2Z isomer, 1H, d, J1–2 ¼ 7.9,
O55CH, H-1). The sample also contained about 6% of the 2E,4Z isomer:

New Phosphonate Reagents
3851
d 6.16 (1H, dd, J1–2 ¼ 7.9 and J2–3 ¼ 15.4, 55CH, H-2), 6.30 (1H, dd,
J4–5 ¼ 11.3, 55CH, H-4), 7.45 1H, dd, J3–4 ¼ 9.8 and J2–3 ¼ 15.1, 55CH,
H-3), 9.63 (1H, d, J1–2 ¼ 7.9, O55CH, H-1). 1H NMR in C6D6 d 0.99 (3H, t,
J10–11 ¼ 7.1, H-11), 1.27–1.32 (8H, m, H-7 to H-10), 1.91 (2H, m, J5–
¼ 7.0, H-6), 5.79 (1H, dt, J5–6 ¼ 7.0 and J4–5 ¼ 15.1, 55CH, H-5), 5.90
6
(1H, dd, J3–4 ¼ 10.7 and J4–5 ¼ 15.1, 55CH, H-4), 6.03 (1H, dd, J1–2 ¼ 7.8
and J2–3 ¼ 15.4, 55CH, H-2), 6.55 (1H, dd, J3–4 ¼ 10.7 and J2–3 ¼ 15.4,
55CH, H-3), 9.54 (1H, d, J1–2 ¼ 7.8, O55CH, H-1). 13C NMR d14.0 (C-11),
22.5 (C-9), 28.5 (C-7), 28.8 (C-8), 31.6 (C-10), 33.2 (C-6), 128.6 (C-4), 130.0
(C-2), 147.4 (C-5), 152.8 (C-3), 193.9 (C-1).
(2E,4E)-N0-(2-Methyl-undeca-2,4-dienylidene)-N,N-dimethyl-
hydrazine (4c)
Compound 4c was prepared in a way similar to compound 3a. The phospho-
nate anion was prepared from 2 (2.36 g, containing 2.31 g of 2, 9.8 mmol) in
THF (25 mL) by treatment with LDA (2.0 M, 5.2 mL, 10.4 mmol, slight
excess), and (2E)-2-nonenal (1.68 g, 12 mmol) was subsequently added.
The mixture was stirred at rt for 20 h. Water (3 mL) was added to quench
the reaction, and the reaction was worked up as before. Kugelrohr distillation
(oven temperature 788C, 0.06 torr) afforded 2.09 g of 4c (85% purity by GC,
yield corrected for purity 82%). By GC and GC-MS, the 2E/2Z isomer ratio
was 39 to 1. MS (EI) m/z (%) 222 (Mþ, 14), 137 (100), 108 (7), 94 (13), 44 (4),
1
43 (5). EI-HRMS C14H26N2 calcd. for 222.2096 (obs. 222.2102). H NMR
d 0.91 (3H, t, J10–11 ¼ 7.0, H-11), 1.29–1.31 (6H, m, H-8 to H-10), 1.43
(2H, m, H-7), 1.96 (CH3 attached to C-2), 2.16 (2H, m, J5–6 ¼ 7.2, H-6),
2.87 (6H, s, N-CH3), 5.77, (1H, dt, J5–6 ¼ 7.2 and J4–5 ¼ 15.1, 55CH,
H-5), 6.12 (1H, d, J3–4 ¼ 11.2, 55CH, H-3), 6.44 (1H, dd, J3–4 ¼ 11.2 and
J4–5 ¼ 15.1, 55CH, H-4), 7.08 (1H, s, 55CH, H-1). 13C NMR d 11.8 (CH3
attached to C-2), 14.1 (C-11), 22.6 (C-10), 28.9 (C-8), 29.4 (C-7), 31.7
(C-9), 33.2 (C-6), 43.2 (N-CH3), 126.7 (C-4), 131.2 (C-2), 133.2
(C-3),135.8 (C-5), 140.0 (C-1).
(2E,4E)-2-Methyl-2,4-undecadienal (4d)
Deprotection procedure was similar to that used for 3b. A solution containing
4c (1.29 g, containing 1.10 g of 4c, 5.0 mmol) and 1 M HCl (50 mL), to which
petroleum ether (bp 35 to 608C, 50 mL) was added after 5 min, was stirred at
room temperature for 48 h. The phases were separated, and the aqueous phase
was returned to the reaction vessel. Petroleum ether (40 mL) was added, and
the mixture was stirred at rt for an additional 1 h before the phases were
separated. Workup of the reaction as for 3b resulted in 0.91 g of the free
aldehyde 4d (purity by GC showed 88%, yield corrected for purity 89%).
The 2E:2Z isomer ratio was 30 to 1. MS (EI) m/z (%) 180 (Mþ, 11), 109
1
(6), 95 (100), 81 (10), 79 (9), 67 (12), 55 (5), 53 (5), 43 (5), 41 (10). H

3852
R. J. Petroski
NMR d 0.91 (3H, t, J10–11 ¼ 6.8, H-11), 1.32–1.34 (6H, m, H-8 to H-10),
1.48 (2H, m, H-7), 1.85 (CH3 attached to C-2), 2.26 (2H, dt, J5–6 ¼ 7.2,
H-6), 6.26 (1H, dt, J4–5 ¼ 15.0 and J5–6 ¼ 7.2, 55CH, H-5), 6.54 (1H, dd,
J3–4 ¼ 11.2 and J4–5 ¼ 15.0, 55CH, H-4), 6.84 (1H, d, J3–4 ¼ 11.2, 55CH,
H-3), 9.44 (major 2E isomer, 1H, s, O55CH, H-1), 10.28 (minor 2Z isomer,
1H, s, O55CH, H-1). The sample also contained a trace amount of the
2E,4Z isomer: d 6.13 (1H, d, J3–4 ¼ 11.2, 55CH, H-3), 6.85 (1H, dd,
J3–4 ¼ 11.2 and J4–5 ¼ 11.3, 55CH, H-4), 9.51 (1H, s, O55CH, H-1). 13C
NMR d14.0 (C-11), 22.5 (C-9), 28.5 (C-7), 28.8 (C-8), 31.6 (C-10),
33.2(C-6), 128.6 (C-4), 130.0 (C-2), 147.4 (C-4), 152.8 (C-3), 193.9 (C-1).
(2E)-N,N-Dimethyl-N0-(3-phenyl-allylidene)-hydrazine (5a)
Compound 5a was prepared in a way similar to compound 3a. The phospho-
nate anion was prepared from 1 (2.22 g, containing 2.06 g of 1, 9.3 mmol) in
THF (25 mL) by treatment with LDA (2.0 M, 5.2 mL, 10.4 mmol, slight
excess), and benzaldehyde (1.11 g, 10.5 mmol) was subsequently added.
The mixture was stirred at rt for 5 h. Water (3 mL) was added to quench the
reaction and the reaction, was worked up as before. Kugelrohr distillation
(oven temperature 618C, 0.1 torr) afforded 1.62 g of 5a (88% purity by GC,
yield corrected for purity 88%). By GC and GC-MS, the 2E/2Z isomer
ratio was 50 to 1. The MS and NMR spectral data were consistent with the
reference spectral data from previous work.[10]
(2E)-Cinnamaldehyde (5b)
Deprotection procedure was similar to that used for 3b. A solution containing
5a (0.98 g, of containing 0.86 g of 5a, 4.9 mmol) and 1 M HCl (50 mL), to
which petroleum ether (bp 35 to 608C, 50 mL) was added after 5 min, was
stirred at room temperature for 18 h. The phases were separated, and the
aqueous phase was returned to the reaction vessel. Petroleum ether (50 mL)
was added, and the mixture was stirred at rt for an additional 1 h before the
phases were separated. Workup of the reaction as for 3b resulted in 0.61 g
of the free aldehyde 5b (purity by GC showed 86%, yield corrected for
purity 81%). The 2E:2Z isomer ratio was 170 to 1. The MS and NMR
spectral data were consistent with the reference spectral data from previous
work.[8]
(2E)-N,N-Dimethyl-N0-(2-methyl-3-phenyl-allylidene)-hydrazine (5c)
Compound 5c was prepared in a way similar to compound 3a. The phospho-
nate anion was prepared from 2 (2.36 g, containing 2.31 g of 2, 9.8 mmol) in
THF (25 mL) by treatment with LDA (2.0 M, 5.2 mL, 10.4 mmol, slight
excess). Benzaldehyde (1.11 g, 10.5 mmol) was subsequently added. The
mixture was stirred at rt for 20 h. Water (3 mL) was added to quench the

New Phosphonate Reagents
3853
reaction, and the reaction was worked up as before. Kugelrohr distillation
(oven temperature 698C, 0.1 torr) afforded 1.82 g of 5c (89% purity by GC,
yield corrected for purity 88%). By GC and GC-MS, the 2E/2Z isomer
ratio was 25 to 1. The MS and NMR spectral data were consistent with the
reference spectral data from previous work.[10]
(2E)-Methyl cinnamaldehyde (5d)
Deprotection procedure was similar to that used for 3b. A solution containing
5c (1.12 g, containing 1.00 g of 5c, 5.3 mmol) and 1 M HCl (50 mL), to which
petroleum ether (bp 35 to 608C, 50 mL) was added after 5 min, was stirred at
room temperature for 48 h. The phases were separated and the aqueous phase
was returned to the reaction vessel. Petroleum ether (40 mL) was added, and
the mixture was stirred at rt for an additional 1 h before the phases were
separated. Workup of the reaction as for 3b resulted in 0.78 g of the free
aldehyde 5d (purity by GC showed 96%, yield corrected for purity 96%).
The 2E:2Z isomer ratio was 56 to 1. The MS and NMR spectral data were con-
sistent with the reference spectral data from previous work.[8]
ACKNOWLEDGMENTS
I thank Karl Vermillion and David Weisleder of National Center for Agricul-
tural Utilization Research (NCAUR) for acquisition of NMR data, Robert
J. Bartelt for helpful discussions, and the University of Illinois, School of
Chemical Sciences, Mass Spectrometry Laboratory, for acquisition of
HRMS data.
REFERENCES
1. Wadsworth, W. S., Jr.; Emmons, W. D. The utility of phosphonate carbanions in
olefin synthesis. J. Am. Chem. Soc. 1961, 83, 1733–1738.
2. Trippett, S.; Walker, D. M. The phosphobetaines: Preparation and properties.
J. Chem. Soc. London 1961, 1266–1272.
3. Schlessinger, H.; Poss, M. A.; Richardson, S.; Lin, P. The vinyligation of
aldehydes: An improved method for the preparation of alpha formylethylidenetri-
phenylphosphorane, and an improved alpha silyl imine reagent of pripionaldehyde.
Tetrahedron Lett. 1985, 26, 2391–2394.
4. Boutagy, J.; Thomas, R. Olefin synthesis with organic phosphonate carbanions.
Chem. Rev. 1974, 74, 87–99.
5. Aboujaoude, E. E.; Collignon, N. A simple synthesis of dialkyl 1-formylalkane-
phosphonates. Synthesis 1983, 634–636.
6. Nagata, W.; Hayase, Y. Formylolefination of organic compounds. J. Chem. Soc.
London (C) 1969, 460–466.

3854
R. J. Petroski
7. Desmond, R.; Mills, S. G.; Volante, R. P.; Shimkai, I. A highly selective method
for the synthesis of (E)-a-methyl-a,b-unsaturated aldehydes. Tetrahedron Lett.
1988, 29, 3895–3898.
8. Bellassoued, M.; Majidi, A. A simple and highly stereospecific route to E-a,b-
unsaturated aldehydes. J. Org. Chem. 1993, 58, 2517–2522.
9. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd edn.;
John Wiley&Sons: New York, 1999; pp. 350–352.
10. Petroski, R. J. Preparation and deprotection of aldehyde dimethylhydrazones.
Synth. Commun. 2006, 36 (120), 1727–1734.
11. Petroski, R. J. Facile biphasic deprotection of aldehyde dimethylhydrazones with
aqueous hydrochloric acid. Lett. Org. Chem. 2007, 4, 452–455.
12. Ford-Moore, A. H.; Perry, B. J. Diisopropyl methylphosphonate. Org. Synth. 1951,
31, 33–35.
13. Bartelt, R. J.; Weisleder, D.; Plattner, R. D. Synthesis of nitidulid beetle phero-
mones: Alkyl-branched tetraene hydrocarbons. J. Agric. Food Chem. 1990, 38,
2192–2196.
14. ACD 1H- and 13C-Predictive software, version 6.0, Advanced Chemistry Develop-
ment, Toronto, Ontario, Canada.
15. Naef, R.; Jaquier, A. New aldehydes and related alcohols in fresh lemon peel
extract (Citrus limon L.). Flavour Fragr. J. 2006, 21, 768–771.