Reaction of [HO(CH 2) 3] 3P with ,β -unsaturated ketones containing a phenylpropanoid backbone

Article abstract of DOI:10.1080/10426507.2013.818997

Interaction of 3,4-(MeO)2-benzylideneacetone with [HO(CH2)3]3P (THPP) was studied in CD3OD by NMR to compare reactivity of a phenylpropanoid ,β-unsaturated ketone with a corresponding ,β-unsaturated aldehyde. In the presence of HCl, both the ketone and a related cinnamaldehyde first establish an equilibrium with the product formed by nucleophilic attack of the THPP at the CO bond, [ArCHCHCX(OD)PR3]⁺Cl^-(XH or CH3, ArPh or 3,4-(MeO)2C6H3). The ketone salt then slowly transforms into [R3PCH(Ar)CH(D)C(O)CD3]⁺Cl^-, the phosphonium product of nucleophilic attack of THPP at the CC bond, whereas the final product from the aldehyde is the (-ether)phosphonium chloride [ArCHCHCH(OCD3)PR3] ⁺Cl^-. In aqueous media, in the absence of HCl, 4-HO-benzylideneacetone, which is similar to a lignin-type, ,β-unsaturated aldehyde model compound, interacts with THPP to afford a stable phosphonium zwitterion, in contrast to the previously studied aldehyde model, which forms dimeric, bisphosphonium products.

Full text of DOI:10.1080/10426507.2013.818997

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Phosphorus, Sulfur, and Silicon and the Related
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REACTION OF [HO(CH2)3]3P WITH α,β-UNSATURATED
KETONES CONTAINING A PHENYLPROPANOID BACKBONE
D. V. Moiseev a b , B. R. James a & A. V. Gushchin b
a Department of Chemistry , University of British Columbia , Vancouver , British Columbia ,
Canada
b Department of Organic Chemistry , Lobachevsky State University of Nizhny Novgorod , Pr.
Gagarina, 23, 603950 , Nizhny , Novgorod , Russia
Accepted author version posted online: 12 Aug 2013.
To cite this article: Phosphorus, Sulfur, and Silicon and the Related Elements (2013): REACTION OF [HO(CH2)3]3P WITH
α,β-UNSATURATED KETONES CONTAINING A PHENYLPROPANOID BACKBONE, Phosphorus, Sulfur, and Silicon and the Related
Elements, DOI: 10.1080/10426507.2013.818997
To link to this article: http://dx.doi.org/10.1080/10426507.2013.818997
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REACTION OF [HO(CH2)3]3P WITH α,β-UNSATURATED KETONES CONTAINING A
PHENYLPROPANOID BACKBONE
D. V. Moiseev,1,2 B. R. James,1 A. V. Gushchin2
1Department of Chemistry, University of British Columbia, Vancouver, British Columbia,
Canada
2Department of Organic Chemistry, Lobachevsky State University of Nizhny Novgorod, Pr.
Gagarina, 23, 603950 Nizhny Novgorod, Russia.
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Abstract Interaction of 3,4-(MeO)2-benzylideneacetone with [HO(CH2)3]3P (THPP) was
studied in CD3OD by NMR to compare reactivity of a phenylpropanoid α,β-unsaturated ketone
with a corresponding α,β-unsaturated aldehyde. In the presence of HCl, both the ketone and a
related cinnamaldehyde first establish an equilibrium with the product formed by nucleophilic
attack of the THPP at the C=O bond, [ArCH=CHCX(OD)PR3]+Cl- (X = H or CH3, Ar = Ph or
3,4-(MeO)2C6H3). The ketone salt then slowly transforms into [R3PCH(Ar)CH(D)C(O)CD3]+Cl-,
the phosphonium product of nucleophilic attack of THPP at the C=C bond, whereas the final
product from the aldehyde is the (α-ether)phosphonium chloride [ArCH=CHCH(OCD3)PR3]+Cl-
. In aqueous media, in the absence of HCl, 4-HO-benzylideneacetone, which is similar to a
lignin-type, α,β-unsaturated aldehyde model compound, interacts with THPP to afford a stable
phosphonium zwitterion, in contrast to the previously studied aldehyde model, which forms
dimeric, bisphosphonium products.
R3P
CD3
Cl
X = CH3
Ar
O
H
D
X
+ R3P + HCl
CD3OD, r.t.
Ar
O
OCD3
PR3
X = H
R = (CH2)3OH
Cl
Ar
X
Keywords (Hydroxyalkyl)phosphines; α,β-unsaturated ketones and aldehydes; phosphonium
salts; phosphonium zwitterions; lignin models
Received………
We thank the Natural Sciences and Engineering Council of Canada for financial support
via a Discovery Grant.
Address correspondence to either Brian James, Department of Chemistry, University of British
Columbia, Vancouver, BC V6L 1Z1, Canada. E-mail: brj@chem.ubc.ca, or Dmitry Moiseev,
Department of Organic Chemistry, Lobachevsky State University of Nizhny Novgorod, Pr.
Gagarina, 23, 603950 Nizhny Novgorod, Russia. E-mail: moisdv@hotmail.com.
2
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INTRODUCTION
Interaction of tertiary phosphines with activated olefins is of importance in organic
synthesis. Scheme 1 exemplifies some syntheses catalyzed by such phosphines, which act as
nucleophiles and attack the C=C bond to generate a carbanionic site; subsequent attack at the
reactant olefin gives, after elimination of the phosphine, a dimerization product (the Rauhut-
Currier reaction, path А);1 in the presence of aldehydes, the carbanion attacks the C=O bond to
afford 1,2-addition products (the Morita-Baylis-Hillman reaction, path B);2 the carbanion can
also be used to generate nucleophiles which then react with the olefin substrate to afford
products with a new С–О3 or С–С bond4 (path C). The activated olefinic substrates are generally
α,β-unsaturated ketones and esters, and nitriles such as acrylonitrile.
We have reported previously on the interaction of tertiary (and secondary) phosphines with
lignin model compounds, including α,β-unsaturated carbonyl compounds,5 in relation to the
discovery of the bleaching activity of water-soluble phosphines on mechanical pulps,6 in which,
for example, cinnamaldehyde derivatives containing OH and/or MeO groups in the aromatic ring
are considered to be a major chromophore responsible for the lignin color.7 Our investigations
revealed that, in aqueous media, the water-soluble phosphine [HO(CH2)3]3P (abbreviated as
THPP) promotes homocondensation of aliphatic aldehydes8 and cross-condensation of
cinnamaldehyde with acetone;5a these reactions are thought to involve generation of ОН- via
nucleophilic attack of THPP at the С=О or С=С bond (see also Scheme 2 below), the OH- anion
then initiating the condensation process. Related to the cinnamaldehyde reaction, in the presence
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of a stoichiometric amount of THPP, this aldehyde undergoes “reductive condensation” to give
two isomeric products (Scheme 2).5a Similar to the Scheme 1 reactions, the first stage of the
process is nucleophilic attack of THPP at the C=C bond and generation of the zwitterion which,
in aqueous media, is in equilibrium with the phosphonium hydroxide. Dimerization of these two
phosphonium species, followed by oxidation of one molecule of THPP (analogous to
decomposition of quaternary phosphonium hydroxides)8,9 and elimination of the second THPP,
leads to the products. Phosphine oxides are also formed in Wittig10, Mitsunobu11 and
Staudinger12 reactions.
The topic of the current paper is interaction of THPP with α,β-unsaturated ketones
containing a phenylpropanoid backbone, as in the aldehyde reactant in Scheme 2, and the
findings reveal some interesting differences. Unsaturated ketones are known to react with tertiary
phosphines (Scheme 1), but generally show low and often different reactivity: for example,
benzylideneacetone (4-phenyl-3-buten-2-one), the closest analogue of cinnamaldehyde, in
MeOH does not afford the corresponding hydro(methoxy) product (Scheme 1, path C),3 and the
divinyl ketone, 5-phenyl-1,4-dien-3-one, the С=С bond of the PhC=C moiety does not
participate in a dimerization reaction (Scheme 1, path А).13
RESULTS AND DISCUSSION
31
The P{1H} spectrum of a 1:1 reaction of THPP with 3,4-(MeO)2-benzylideneacetone (I)
in CD3OD (r.t., Ar) after 20 min showed a new, low intensity singlet (~3% of the THPP
resonance at P –29.5) at P 39.1, and this is attributed to the phosphonium cation III (Scheme
1
3).5b The H NMR data revealed relatively fast H/D-exchange of the H1 and CH3 protons in the
3
reactant ketone (Scheme 4); e.g. after the 20 min, the intensity of the H1 doublet (H 6.68, JHH
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16.2 Hz) is ~3% of that of the H2 resonance, which is seen as a broad singlet at H 7.58 that
31
disappears slowly over 4 days. During this time, the P{1H} spectrum is essentially unchanged
except for the appearance of
a
weak singlet at P –29.8, possibly due to
[DO(CH2)3]2P[CH(D)(CH2)2OD], the phosphine monodeuterated in the -position. H/D-
31
exchange of a proton  to the P-atom typically shifts the P{1H} resonance upfield by up to ~
0.3 ppm,5e,8,14 whereas such exchange of a PH proton, for example, as in (DOCH2)2PH and
DOCH2P(D)H, gives upfield shifts of 1.6 and 1.1 ppm, respectively.15 The low-resolution MS-EI
of a residue from the reaction (dissolved in MeOH) revealed main peaks at m/z 211 (75%, [M])
and 193 (100%, [M – CD3]), which correspond to the fully deuterated ketone I-D5.
In the presence of less THPP (8 mol%), the Н/D-exchange slows down. Figure 1 shows the
loss of intensity of the H1, H2 and CH3 proton signals with time, relatively to the “stable” signals
of the aromatic protons. After 15 min, a triplet (H 2.33, 2JHD 2.2 Hz) due to CH2D was detected
near the singlet of the CH3 protons (H 2.35); after 3 h, the CH3 resonance has almost
2
disappeared, and a quintet (H 2.32, JHD 2.2 Hz) due to the CHD2 group is apparent. Figure 1
shows that the rate of the H/D-exchange of the H1 and CH3 protons is essentially identical and,
after ~20 h, the intensity of both these proton signals levels out at ~3–4%. The H/D-exchange of
the H2 proton is again slow and, after 3 days, the signal intensity is reduced by only ~20%. The
31P{1H} spectrum of the reaction mixture again revealed the resonances of THPP and small
amounts of the phosphonium cation (P 39.1) throughout the 72 h experiment. The low-
resolution MS-EI of a residue obtained from the reaction after this time showed main peaks at
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m/z 210 (80%, [M]) and 192 (100%, [M – CD3]), which correspond to the deuterated ketone I-
D4.
The H/D-exchange of the ketone-CH3 protons is likely due to the keto-enol tautomerism
catalyzed by a base and facilitated by С=СС(OD)=С conjugation.16 The fast exchange of H1 is
due to reversibility of the nucleophilic attack of THPP at the C=C bond (Scheme 5). The strong
base CD3O- generated is thought to lead to reversible formation of the ylide and thus to the slow
exchange of H2 (Scheme 6). Exchange of the α-proton of the THPP hydroxypropyl group can
also occur via a similar ylide intermediate.8,14
In the corresponding reaction of THPP with 3,4-(MeO)2-cinnamaldehyde (1:1, CD3OD,
r.t., Ar), the fast H/D-exchange of the α-H and the slow exchange of the β-H of the С=С bond
were similarly observed. In the 31P{1H} spectrum, a low intensity, broad singlet at P 38.1 (~9%
of the THPP resonance) was detected. This system, however, is unstable, and the P 57.3 singlet
1
of THPP=O appears, this coinciding with a more complex H spectrum. The findings are closely
related to those found for generation of this oxide (P 61.3 in D2O)5a,8 in aqueous redox systems,
where cinnamaldehyde undergoes ‘reductive condensation’ (Scheme 2)5a and 3,4-(MeO)2-
benzaldehyde is converted to the benzyl alcohol.8
The 1:1 reaction of I with THPP hydrochloride (THPPH+Cl-) in CD3OD (r.t., Ar) differs
from that with THPP in that, although the CH3 protons of the ketone again undergo D-exchange
within 30 min, the product is the ketone I-D3 (see Scheme 7) which then reacts further. The
31P{1H} spectrum after the 30 min (Figure 2A) shows the reactant phosphonium cation
1
[DO(CH2)3]3P+D (t, P 19.5, JPD 78 Hz – very similar to the data in D2O)5a,8 and three new
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1
species in the phosphonium region (P 46.3, 38.4 and 37.6). Analysis of the accompanying H
spectrum reveals that the P 46.3 signal pertains to species IV formed via nucleophilic attack of
THPP at the carbonyl carbon of I-D3 (Scheme 7). The H1 and H2 vinyl protons are seen as two
doublets of doublets centered at H 6.22 (3JPH 3.8 Hz) and 6.85 (4JPH 5.0 Hz), respectively, with
3
4
3
the JHH value of 16.2 Hz implying a trans conformation;17 that JPH is > JPH is not unusual
within such phosphonium species.5a The maximum relative concentration of IV (~20%) is seen
within 1 h of the reaction (Figs. 2 and 3). Nucleophilic attack at the C=O bond was found also
for the reaction of THPP with cinnamaldehyde in aqueous media in the presence of HCl5a and in
MeOH (see below); secondary phosphines and tertiary mono(α-hydroxyalkyl)phosphines also
preferably attack the C=O bond of α,β-unsaturated aldehydes.5d
As IV disappears in the solution, the P 38.4 signal becomes more intense and reaches a
maximum concentration of ~35% after 8 h (Fig. 3), which is assigned to the enol species V
1
(Scheme 8). The H spectrum of this species shows two doublets of doublets at H 4.70 (2JPH
=
3
16.2, 3JHH = 11.0 Hz) and H 4.98 (3JPH = 7.9, JHH = 11.0 Hz); the former is due to H2, the 2JPH
value being typical for protons adjacent to a phenyl ring and a phosphonium cation,5a,5b,5e,14 and
the latter is assigned to the H1 proton  the closest analogy that we could find for the latter is the
3
3
H 5.02 value (with JPH = 7.1 Hz, and JHH = 12.3 Hz coupling to a benzyl proton) for the
corresponding proton of the enol Ph2PCH(Ph)CH=CH(OH), detected in the 1:1 reaction of
cinnamaldehyde with Ph2PCH(OH)Ph in CD3OD.5d Of note, there is a further analogy with this
31
hydroxyphosphine system,5d in that the P{1H} NMR profile of the reaction is similar to that
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seen here for the ketone/THPP/HCl reaction (Figs. 2 and 3); in the hydroxyphosphine reaction,
the Ph2PCH(Ph)CH=CH(OH) and a co-product, PhCH(OH)CH=CH(PPh2), were considered to
be formed by migration of PPh2 and OH, respectively, within a detected intermediate
PhCH=CHCH(OH)PPh2, and so similarly V could be formed via migration of the THPP moiety
within IV (Scheme 9). In this case, the minor, unassigned resonance at P 37.6 (Fig. 2, A and B)
might be associated with an intermediate such as VI (Scheme 9).
Other reasonable pathways for formation of V are shown in Scheme 8. In path A, a
carbocation generated at the benzyl C-atom of the ketone would contain the enol moiety, and
subsequent nucleophilic attack of THPP would give V; in path B, attack of THPP at the C=C
bond would generate an intermediate phosphonium carbanion, with subsequent deuteron capture
generating the final product, a mixture of VII-D4 and associated hemiketal VIII-D8 (see below,
Scheme 10), but in this case V would not be detected, and so B is not considered a major
pathway.
During the course of the ketone/THPPH+Cl- reaction in CD3OD (Figs. 2 and 3), the enol V
slowly transforms into the ketone VII-D4, which is monodeuterated in the α-position (Scheme
10) and, under these conditions, this is in equilibrium with the hemiketal VIII-D8 (see below);
the 31P{1H} spectrum shows respective signals at P 39.1 and 39.9 (see below), and the VII-D4 :
VIII-D8 ratio of 3:2 is, as expected, constant within Figures 2BD. [Note that the P 39.1 value is
the same as that seen for III (Scheme 3), in which the Me is non-deuterated.]
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The same ketone/THPPH+Cl- reaction was carried out in MeOH. After 48 h, the solvent
was removed and an isolated residue showed a single MS-ESI+ peak at m/z 415.0, corresponding
to the nondeuterated phosphonium cation VII (Scheme 11). The 31P{1H} spectrum of a D2O
solution of the residue was unchanged over time, and revealed one singlet at P 39.0, and the 1H
spectrum confirmed formation of VII: H 2.22 (s, CH3), 4.35 (HM), 3.73 (HA, which overlaps
with the CH2OD resonance), and 3.28 (HB). The HM, HA and HB resonances form a MABX
pattern due to additional coupling to the P-atom: JMA = 11.2, JMB = 3.2, JAB = 18.1, ΔMA = 185.8,
ΔAB = 132.9, JXM = 15.4, JXA = 5.9, JXB = 9.0 Hz. Formation of phosphonium salts analogous to
VII has been reported by
31
others.3,18 The P{1H} spectrum of the residue in CD3OD solution initially revealed singlets at
P 39.9 and 39.1 in a 1:8 ratio and, over 24 h, their intensities changed and became roughly
1
equal. The initial H spectrum, associated with the P 39.1 species, is similar to that in D2O and
corresponds to that of VII: H 2.18 (s, CH3), 4.36 (HM), 3.60 (HA, which again overlaps with the
CH2OD resonance), and 3.25 (HB); the MABX pattern is simulated using JMA = 10.4, JMB = 3.4,
JAB = 18.0, ΔMA = 225.4, ΔAB = 105.0, JXM = 15.2, JXA = 6.8, JXB = 10.5 Hz. The protons of VII-
1
D4 (Scheme 10) are seen in the H spectrum as two three-spin systems, MAX and MBX, in an
integration ratio of ~4:3 for the two distereoisomers present; the spectra are well simulated by
the parameters: (HM) 4.35, (HA) 3.58, JMA = 10.4, ΔMA = 230.0, JXM = 15.2, JXA = 6.2 Hz, and
(HM) 4.35, (HB) 3.23, JMB = 3.4, ΔMB = 336.3, JXM = 15.2, JXB = 10.3 Hz. The chirality at the
31
methylene C-atom does not affect the P{1H} spectrum, which shows just the one singlet at P
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39.1. Nucleophilic attack of CD3OD at the C=O of VII-D4 to afford the third chiral center in
31
VIII-D8 is apparently stereospecific because only one P resonance is seen at P 39.9. That this
1
is due to the hemiketal VIII (Scheme 11) is supported further in that the linked, analyzable H
resonances are shifted upfield from those assigned for VII, consistent with conversion of C=O to
C–OD; e.g., the CH3 singlet is seen at H 1.04, and the CHM multiplet is shifted to H 3.92 (JMA
=
7.6, JMB = 4.0, JXM = 16.6 Hz), which now overlaps with the resonance of the MeO substituent in
the aromatic moiety of VII. The HA and HB signals are hidden by the more intense resonances of
the CH2CH2 protons of the THPP. Of interest, hemiacetals formed from addition of CD3OD to
the corresponding α,β-unsaturated aldehyde derivatives are a mixture of diastereomers with
different 1H and 31P{1H} chemical shifts.5d,5e,19
The 1:1 reaction of THPPH+Cl- with cinnamaldehyde in CD3OD under Ar at r.t., like the
benzylideneacetone system, involves nucleophilic attack at the C=O bond, with the two
equilibria outlined in Scheme 12 being established by NMR data: that between aldehyde and
hemiacetal (IX), and that between aldehyde and the (α-deuteroxy)phosphonium salt (X), which
then very slowly converts to the (α-ether)phosphonium chloride [PhCH=CHCH(OCD3)PR3]+Cl-
(XI) (Scheme 12). After 2 h, only trace aldehyde is seen in the 1H spectrum, in which the H1, H2
and H3 protons of both IX and X are readily indentified. Figure 4, taken after 16 days when some
XI has also been formed, shows the well resolved proton signals that, as illustrated, are readily
31
1
assigned. The P{1H} spectrum after 2 h shows the triplet of [DO(CH2)3]3PD+ (P 19.5, JDP
=
78 Hz) and the singlet of X (P 38.0) in about a 1:1 ratio. These resonances slowly disappear and
are replaced by a singlet at P 38.5, attributed to the final product XI (Scheme 12); after 37 days
the XI/X ratio is ~ 8. After removal of the solvent at this stage, the MS-ESI+ of a residue
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(dissolved in MeOH) showed the main peak at m/z 358.3 (100%) corresponding to the
phosphonium cation of XI. Of note, and in contrast, in aqueous media the 1:1 reaction between
THPPH+Cl- and cinnamaldehyde (1:1) leads to the final product R3P+CH(Ph)CH2CH(OH)2,
formed by nucleophilic attack at the C=C bond, although intermediate X was observed as the
analogous (α-hydroxy)phosphonium salt.5a
A 1:1 reaction of 4-HO-benzylideneacetone with THPP in D2O (r.t., Ar) rapidly gives the
phosphonium zwitterion XII-D5, which is likely in fast equilibrium with the phosphonium
deuteroxide XIII-D5 (Scheme 13). Just one singlet (P 37.8) is seen in the 31P{1H} spectrum, and
the 1H spectrum shows just a doublet at H 4.17 due to the H2 proton (2JPH = 14.6 Hz), the H1 and
CH3 protons having been replaced by deuterons (cf. the 1st step of Schemes 25a,b and 4). The MS-
ES+ spectrum in MeCN of a reaction residue showed peaks at m/z 373.3 (90%), 374.3 (100%),
375.3 (95%) and 376.3 (55%) of which the highest corresponds to XII-D5 protonated at the
phenoxide oxygen; the lower mass peaks are thought to result from H/D-exchange caused by
trace water in the MeCN. In contrast to the zwitterions derived from α,β-unsaturated aldehydes
(Scheme 2),5a,b XII-D5/XIII-D5 are stable under the reaction conditions and do not undergo
dimerization.
A 1:1 reaction of 4-HO-benzylideneacetone with THPP in acetone (r.t., Ar) again generates
XII, but now slowly, and it precipitates as a yellow solid (Scheme 14), similar to reactivity
shown by lignin-type, α,β-unsaturated aldehydes such as coniferaldehyde and sinapaldehyde.5e
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The 31P{1H} spectrum of XII in D2O shows a singlet at P 37.8, the same as that observed for
1
the corresponding reaction in D2O (see above). The initial H spectrum reveals a singlet at H
2.23 for the CH3 protons, and broadened doublets at H 4.22 (the H2 proton) and H 3.20 (one of
the CH2 protons). Over 24 h, H/D exchange occurs and the CH2 signals disappear, while the CH3
singlet is replaced by a quintet assigned to CD2H. The MS-ESI+ spectrum (MeCN solution)
revealed the main peak at m/z 371.3, corresponding to the protonated phosphonium cation of
XII. The elemental analysis for XII is in reasonable agreement with the calculated values, but
this is likely fortuitous because the 1H data also show a significant amount of the reactant ketone,
1
and this is not due to dissociation of XII in solution since no H signals of THPP are seen; co-
precipitation of ketone as an anion (formed via deprotonation of the phenolic-OH) with the
protonated XII as a phosphonium cation seems plausible.
CONCLUSIONS
Thus, 3,4-(MeO)2-benzylideneacetone, an example of α,β-unsaturated ketones containing a
phenylpropanoid backbone and closely related to lignin-type, α,β-unsaturated aldehydes, reacts
with [HO(CH2)3]3P in methanol to give within an equilibrium the phosphonium cation
R3P+CH(Ar)CH2C(O)CH3; at room temperature, the equilibrium strongly favours the reactants
but is detected by H/D-exchange in CD3OD. The presence of HCl shifts the equilibrium to the
product [R3P+CH(Ar)CH2C(O)CH3]Cl-, formation of which occurs via the (α-
hydroxy)phosphonium intermediate [ArCH=CHC(CH3)(OH)PR3]+Cl- and the enol
[R3P+CH(Ar)CH=C(OH)CH3]Cl-. Similar reaction with cinnamaldehyde affords only the (α-
ether)phosphonium salt [PhCH=CHCH(OMe)PR3]+Cl-. Similar to lignin-type, α,β-unsaturated
aldehydes containing a p-OH substituent, 4-HO-benzylideneacetone quantitatively reacts with
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[HO(CH2)3]3P in aqueous media to afford the zwitterion R3P+CH(C6H4-O-)CH2C(O)CH3 which,
unlike phosphonium zwitterions derived from lignin-type aldehydes, is stable in water.
EXPERIMENTAL
General. Cinnamaldehyde and 4-OH-benzylideneacetone were purchased from Aldrich
and used as received. 3,4-(MeO)2-benzylideneacetone and 3,4-(MeO)2-cinnamaldehyde were
prepared by condensing 3,4-(MeO)2-benzaldehyde (Aldrich) with acetone and with acetaldehyde
(Aldrich), respectively. Tris(3-hydroxypropyl)phosphine (THPP, an oil, ~85% from Strem
Chemicals) was used without purification. We have discussed the difficulty in attempts to purify
THPP because of impurities that are “closely related” phosphines;8 the phosphonium
hydrochloride, {[HO(CH2)3]3PH}+Cl- (abbreviated THPPH+Cl-) was prepared as described.8
Distilled water and D2O were saturated with Ar for 3 h under stirring; organic solvents were
dried over the appropriate agents, distilled under N2, degassed and then saturated with Ar.
CD3OD (Cambridge Isotope Laboratories) was used as received. NMR spectra were recorded at
~300 K on Bruker AV400 (400 MHz for 1H, 161 MHz for 31P) or AV300 (300 MHz for 1H; 121
MHz for 31P{1H}) instruments, with a residual deuterated solvent proton and 85% aq. H3PO4
1
1
being used as references; s = singlet, d = doublet, t = triplet, m = multiplet. H and H{31P}
spectra were simulated using the gNMR Version 4 program, with J values to ± 0.3 Hz. Mass
spectrometry was performed on a Kratos MS-50 (EI) or on a Bruker Esquire electrospray (ESI)
ion trap instrument with samples dissolved in MeOH or MeCN, with positive ion polarity,
scanning from 1001000 m/z. The elemental analysis of XII was carried out in this department
by M. Lakha using a Carlo Erba 1108 analyzer.
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NMR investigations of 1:1 reactions of THPP with organics. In a glove-box, THPP
(25 mg, 0.12 mmol, assuming 100% purity) was added to a solution of 3,4-(MeO)2-
benzylideneacetone
(25 mg, 0.12 mmol) in CD3OD (1.1 mL), and a sample (~0.7 mL) of the solution was placed
under Ar in a J-Young NMR tube; NMR spectral changes were then monitored as a function of
time. The same reaction with less THPP (2 mg, 0.01 mmol) was performed similarly. The 1:1
reactions of THPP with 3,4-(MeO)2-cinnamaldehyde (23 mg, 0.12 mmol) in CD3OD, and with
4-HO-benzylideneacetone (19 mg, 0.12 mmol) in D2O (1 mL) were also studied in the same
way, as were the 1:1 reactions in CD3OD (1.1 mL) of THPP hydrochloride (12 mg, 0.05 mmol)
with 3,4-(MeO)2-benzylideneacetone (10 mg, 0.05 mmol), and of THPP hydrochloride (22 mg,
0.09 mmol) with cinnamaldehyde (11 μL, 0.09 mmol).
Synthesis of the phosphonium salt, XII (Scheme 14). A r.t. reaction of a stirred mixture
of THPP (100 mg, 0.48 mmol) with 4-HO-benzylideneacetone (77 mg, 0.48 mmol) was carried
out in acetone (1.5 mL), when a yellow precipitate was formed after 24 h. This was collected,
washed with acetone (2  2 mL), and dried under vacuum overnight; yield ~100 mg, ~70% based
on ~85% purity of THPP. Anal. Calcd. for C19H31O5P (370.42): C 61.61; H 8.43. Found: C 61.2;
H 8.4. 1H and 31P{1H} NMR data in D2O are discussed in the Results and Discussion section.
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REFERENCES
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2122.
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Figure 1. Decreasing intensity (%) of the protons H1, H2 and CH3 of the ketone I in CD3OD in
the presence of 8 mol% THPP.
R3P+D
IV
V
P 37.6
A
B
C
D
VII-D4
VIII-D8
ppm
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44
42
40
38
36
34
32
30
28
26
24
22
20
18
16
Figure 2. The 31P{1H} spectrum of the 1:1 reaction of the ketone I and THPP hydrochloride
(CD3OD, r.t., Ar) after: (A) 30 min, (B) 5 h, (C) 24 h, (D) 72 h; R = (CH2)3OD.
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100
80
VII-D4 + VIII-D8
R3P+D
60
40
IV
V
20
P 37.6
0
0
10
20
30
40
50
60
T ime, h
Figure 3. Relative concentration of phosphorus-containing species in the course of the reaction
of THPP hydrochloride with the ketone I (1:1, CD3OD, r.t., Ar; R = (CH2)3OD).
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H2 of XI
H 6.31
H2 of X
H 6.42
H3 of XI
H 7.06
H1 of XI
H 5.14
3JPH 4.3
3JHH 15.8
3JHH 8.4
3JPH 4.0
3JHH 15.8
3JHH 6.9
4JPH 4.1
3JHH 15.8
3JHH ≈ 2JPH ≈ 8.5
4JHH 0.9
H1 of IX
H 4.93
3JHH 5.1
4JHH 1.1
H3 of IX
H3 of X
H 7.02
4JPH 4.1
3JHH 15.8
H2 of IX
H 6.16
H 6.73
H1 of X
H 5.45
3JHH 16.2
3JHH 16.2
3JHH 5.1
3JHH ≈ 2JPH ≈ 6.8
4JHH 1.3
7.00
6.50
6.00
5.50
5.00
ppm
1
Figure 4. A part of the H spectrum of the reaction between THPP hydrochloride and
cinnamaldehyde (1:1, CD3OD, r.t., Ar) recorded after 16 days.
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Nu
X
X
X
X
+ NuH
R3P
+
- NuH
R3P
R3P
X
X
X
(A)
O
H
R'
O
X
R'
OH
X
R'
OH
X
R'
X
+ NuH
R3P
R3P
R3P
+
X
- NuH
R3P
R3P
Nu
(B)
(C)
X
+ NuH
+ NuH
Nu
R3P
Nu
+
Nu
+
Nu
X
X
X
Scheme 1 Reactions catalyzed by R3P; X = electron-withdrawing group; NuH = proton donor
O
R3P
Ph
R3P
Ph
OH
H2O
Ph
O
Ph
+
+ R3P
O
Ph
H2O, r.t.
O
O
Ph
Ph
Scheme 2 Reaction of [HO(CH2)3]3P with cinnamaldehyde;5a r.t. = room temperature (~20 °C)
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CD3O
O
O
O
R3P
R3P
MeO
MeO
MeO
MeO
MeO
MeO
CH3
CH3
CH3
CD3OD
+ R3P
D
I
II
III
Scheme 3 Reaction of THPP with 3,4-(MeO)2-benzylideneacetone
H2
H2
O
D
O
O
MeO
MeO
MeO
MeO
MeO
MeO
CD3
CD3
THPP (1 eq)
CH3
slow
H1
CD3OD, r.t., Ar
fast
D
D
I-D4 (M = 210.12)
I-D5 (M = 211.12)
I
Scheme 4 H/D exchange in 3,4-(MeO)2-benzylideneacetone
H2
H2
O
R3P
O
R3P
O
O
D
CD3OD
CD3O
+ R3P
Ar
CD3
Ar
CD3
Ar
CD3
Ar
CD3
H2
H2
H1
H1
H1
D
Scheme 5. Fast H/D exchange; R = (CH2)3OD, Ar = 3,4-(MeO)2C6H3
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R3P
D
O
D
O
R3P
O
R3P
O
D
D
D
D
D
D
CD3O
CD3OD
CD3O
Ar
CD3
Ar
CD3
Ar
CD3
Ar
CD3
H2
CD3OH
D
Scheme 6 Slow H/D exchange; R = (CH2)3OD, Ar = 3,4-(MeO)2C6H3
2
O
CD3
OD
H
+ R3P + DCl
Ar
Ar
CD3
PR3
Cl
1
H
I-D3
IV
Scheme 7 Reaction of I with THPP and HCl in CD3OD; R = (CH2)3OD, Ar = 3,4-
(MeO)2C6H3
OD
CD3
OD
CD3
R3P
D
Ar
Ar
(A)
(B)
R3P
OD
CD3
O
Ar
Ar
CD3
H2
H1
R3P
R3P
O
O
D
R3P
V
Ar
Ar
CD3
CD3
Scheme 8 Plausible pathways for formation of V; R = (CH2)3OD, Ar = 3,4-(MeO)2C6H3
2
OD
PR3
CD3
CD3
OD
R3P
Ar
OD
CD3
H
Ar
Ar
2
2
PR3
H
H
1
1
1
H
H
H
VI
IV
V
Scheme 9 Formation of V via VI; R = (CH2)3OD, Ar = 3,4-(MeO)2C6H3
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OCD3
R3P
Ar
OD
CD3
R3P
O
R3P
D
D
Ar
Ar
CD3
CD3
OD
2
2
2
H
H
H
1
1
1
H
H
H
V
VII-D4
VIII-D8
Scheme 10 Transformation of V; R = (CH2)3OD, Ar = 3,4-(MeO)2C6H3; the D-count in V
does not include the D-atoms in the R3P moiety.
R P
R P
OCD3
OD
O
O
Cl
Cl
X
X
3
3
+ CD3OD
HB
HB
+ R3P + HCl
Ar
Ar
Ar
H
H
M HA
M HA
I
VII
VIII
Scheme 11 Reaction of I with THPP and HCl in MeOH; R = (CH2)3OH, Ar = 3,4-(MeO)2C6H3
H3
OCD3
OD
CD3OD
H1
H2
IX
O
Ar, r.t.
H3
H3
PR3 Cl
PR3 Cl
OD
H1
OCD3
H1
R3P, DCl
+ CD3OD
- D2O
H2
H2
X
XI
Scheme 12 Reaction of cinnamaldehyde with THPP and HCl in CD3OD; R = (CH2)3OD
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H2
O
R3P
O
R3P
O
DO
D
D
D
D
CD3
+ D2O
CD3
H2
+
R3P
H2
H1
D2O, r.t., Ar
HO
O
DO
XII-D5
XIII-D5
Scheme 13 Reaction of 4-OH-benzylideneacetone with THPP in D2O; R = (CH2)3OD; the D-
count in XII-D5 and XIII-D5 does not include the D-atoms in the R3P
H2
O
R3P
O
H
H
CH3
H2
+
R3P
H1
Acetone, r.t., Ar
moiety. HO
O
XII
Scheme 14 Reaction of 4-OH-benzylideneacetone with THPP in acetone; R = (CH2)3OH
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