Michael Addition of P-Nucleophiles to Conjugated Nitrosoalkenes

Article abstract of DOI:10.1021/acs.joc.9b00924

A general approach to various α-phosphorus-substituted oximes (β-oximinoalkyl-substituted phosphonates, phosphine oxides, phosphine-borane complexes, and phosphonium salts) was developed. The strategy exploits hitherto unknown Michael addition of PH-containing compounds (diphenylphosphine oxide, diisopropyl phosphite, phosphine-borane complexes, and triphenylphosphonium bromide) to unstable conjugated nitrosoalkenes, which are generated in situ from corresponding nitrosoacetals. The resulting α-phosphorus-substituted oximes can be considered as useful P-, N-, and O-ligands for catalysis and precursors to valuable β-aminophosphonates.

Full text of DOI:10.1021/acs.joc.9b00924

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Article
Michael Addition of P-nucleophiles to Conjugated Nitrosoalkenes
Yana A. Naumovich, Sema L. Ioffe, and Alexey Yu. Sukhorukov
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 07 May 2019
Downloaded from http://pubs.acs.org on May 7, 2019
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Michael Addition of P-nucleophiles to Conjugated Nitrosoalkenes
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Yana A. Naumovich,a Sema L. Ioffe,a Alexey Yu. Sukhorukov,a,b,c,*
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a
N. D. Zelinsky Institute of Organic Chemistry, Leninsky prospect, 47, Moscow, Russia,
119991
b
Higher Chemical College, D. Mendeleev University of Chemical Technology of Russia,
Miusskaya sq., 9, Moscow, Russia, 125047
c Plekhanov Russian University of Economics, Stremyanny per. 36, Moscow, Russia, 117997
* sukhorukov@ioc.ac.ru
X
P R
R
HO
O
H
X
N
N
precursor
P R
R
1,4-addition
33 - 95 %
NSA
19 examples
X = O, BH3, Ph
R = Ph, OAlk
 diphenylphosphine oxide  dialkyl phosphites
 PH-phosphonium salts  phosphine-boranes
Abstract
A general approach to various -phosphorus-substituted oximes (-oximinoalkyl-substituted
phosphonates, phosphine oxides, phosphine-borane complexes and phosphonium salts) was
developed. The strategy exploits hitherto unknown Michael addition of PH-containing
compounds (diphenylphosphine oxide, diisopropyl phosphite, phosphine-borane complexes and
triphenylphosphonium bromide) to unstable conjugated nitrosoalkenes, which are generated in
situ from corresponding nitrosoacetals. The resulting -phosphorus-substituted oximes can be
considered as useful P,N,O-ligands for catalysis and precursors to valuable -
aminophosphonates.
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Introduction
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Michael addition to conjugated nitrosoalkenes (NSA) is a promising approach to various -
substituted oximes, which are highly useful intermediates in organic synthesis.1 This strategy is
considered as an umpolung version of the conventional approach based on electrophilic addition
to enolates followed by oximation.1h,2 However, NSA are labile species, which tend toward
polymerization and other side reactions.1b Successful coupling of nitrosoalkenes with
nucleophiles is challenging and depends on many factors such as solvent, temperature,
concentration and, especially, the nature of the NSA precursor.1g Nevertheless, much research
has been done in the recent years to elaborate convenient methods for the Michael addition of
various C-,3 N-,4 O-5 and S-nucleophiles2,6 to NSA.
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On the other hand, the use of P-nucleophiles in this methodology was left unexplored to the best
of our knowledge.7 Addition of P-nucleophiles to NSA would lead to -phosphorus-substituted
oximes, which can be exploited as useful P,N,O-ligands8 for catalysis9 as well as precursors to
molecules relevant to pharmaceutics and agrochemicals,10 such as -aminophosphonates11 and -
hydroxylaminophosphonates12 (Scheme 1). Therefore, in this paper, we describe our studies on
the Michael addition of various P-nucleophiles to NSA, which led to the development of new
methods for the synthesis of -oximinoalkyl-substituted phosphonates (X = O), phosphine
oxides and phosphites (X = O), phosphine-borane complexes (X = BH3) and phosphonium salts
(X = R). It is worthy of mention, that the synthesis of -phosphorylated oximes via NSA have
been described by Palacios et al,13 however nitrosoalkenes already bearing a phosphorous-
containing group were used in this strategy (Scheme 1). Other methods for the synthesis of -P-
substituted oximes exploit oximation of corresponding aldehydes/ketones,14 addition of
hydroxylamine to allenyl-substituted phosphine oxides,15 SN2 reactions of O-protected -
halooximes with tri-substituted phosphines,16 dehydration of -hydroxylamine-substituted
phosphonium salts,17 and addition of Wittig phosphine ylides to nitrile oxides.7b However, these
approaches are not general and have been devised to access specific types of organophosphorous
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derivatives of oximes. The method developed here allows the preparation of various classes of
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organophosphorous compounds exploiting a single precursor (an NSA derivative).
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Scheme 1. Suggested approach to -phosphorus-substituted oximes and their applications
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This work:
X
P R
HO
O
H
X
R
N
N
precursor
P R
R
1,4-addition

X = O, BH3, Ph
R = Ph, OAlk
NSA
Palacios et al:13
O
HO
N
N
O
HO
O
N
Nu
base

Br
P R
R
P R
R
P R
R
Nu
O
Utility of -P-substituted oximes

HO
HO
O
NH
O
O
NH2
N
[H]
or
P R
R

P R
R
P R
R
-aminophosphonates
L
L
L
M
L
HO
HO
M
N
O
P
N
P R
R
R
R
P,O,N-ligands
Results and discussion
The way how NSA are generated is essential for achieving a successful Michael addition and for
prevention of side reactions. Conventional precursors of NSA are α-halooximes 1,1a,1b,18 which
undergo deprotonation/elimination of the halide anion upon treatment with a Brønsted base
(Scheme 2). However, under these conditions NSA are generated at high concentrations, thus
facilitating side processes such as polymerization.5b More convenient NSA precursors are
quaternary ammonium salts 2,19 silyl ethers of α-halooximes 3,3a,3b,18b and nitrosoalkene acetals
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4.5b,6a,20 Silylated derivatives 3 and 4 liberate NSA upon the action of Lewis bases, which attack
silicon atom enabling the subsequent elimination reaction. By changing the Lewis base, the rate
of the formation of NSA can be affected. Compounds 1-3 are typically prepared from
corresponding -haloketones, while ene-nitrosoacetals 4 are accessed by double silylation of
aliphatic nitro compounds.20 In our studies aimed at achieving Michael addition of P-
nucleophiles to NSA, all four types of nitrosoalkene precursors were examined.
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Scheme 2. Precursors of NSA
HO
TBSO
N
N
Hal
R1
Cl
R1
R2
R2
base
base
3
LB
LB
1
O
N
R1
R2
HO
NSA
N
TMSO
OTMS
R2
N
NEt3 Cl
R1
R1
R2
4
2
LB - Lewis base
Initially, we explored Michael addition of diphenylphosphine oxide (R = Ph) and diisopropyl
phosphite (R = OiPr) with model precursors 1a-4a in DMF under conditions used to generate
NSA. Results are summarized in Table 1.
Table 1. Reaction of NSA precursors 1a-4a with diphenylphosphine oxide and diisopropyl
phosphite
HO
Me
O
conditions
N
O
P
R
N
R2P(O)H
precursor
1a-4a
then
MeOH
R
Me
0 C to rt
R1 = Me
R2 = H
5a
, R = Ph
i
6a
, R = O Pr
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Entry NSA
precursor
Conditions
R
Yield, %a
5
6
7
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9
Ph
0 (5a)b
1
1a
DMF, no additives
DMF, Et3N
OiPr 0 (6a)c
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Ph
traces (5a)b
2
1a
1a
2a
2a
2a
3a
3a
3a
3a
4a
OiPr 0 (6a)a
Ph
OiPr 0 (6a)c
0 (5a)b
OiPr 0 (6a)c
0 (5a)b
OiPr 0 (6a)c
88 (5a)b
OiPr 5 (6a)c
0 (5a)b
OiPr 0 (6a)c
0 (5a)b
OiPr 0 (6a)c
23 (5a)b
3
DMF, K2CO3
DMF, no base
DMF, Et3N
Ph
4
Ph
5
Ph
6
DMF, K2CO3
DMF, no base
DMF, Et3N
Ph
7
Ph
8
Ph
89 (5a)b,d
9
DMF, K2CO3
DMF, TBAF
DMF, no additives
OiPr 3 (6a)c
Ph
OiPr 16 (6a)c
81 (5a)b
49 (5a)b
10
11
Ph
OiPr 38 (6a)c
a
1
Precursors 1a-4a: R1 = Me, R2 = H, Hal = Cl. Yield was determined by H NMR with internal standard
b
c
d
(trichloroethylene). 2 equiv. of NSA precursor were used. 1 equiv. of NSA precursor was used. Mixture of 5a
with its TBS ether (ratio 1 : 1.5).
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As can be seen from these data, the formation of Michael addition product could be achieved
both with diphenylphosphine oxide and diisopropyl phosphate. However, the nature of NSA
precursor proved to be crucial. No C,P-coupling products were obtained with chloroacetone
oxime 1a both with and without Et3N additive (entries 1 and 2, Table 1). When K2CO3 was used
as base, a small amount (23 %) of phosphine oxide 5a was observed, yet no adduct with
diisopropyl phosphite was detected (entry 3, Table 1). Less reactive quaternary salt 2a afforded
corresponding phosphine oxide 5a in high yield in the presence of K2CO3, however, only 5 % of
phosphonate 6a were detected in a same reaction with diisopropyl phosphite (entry 6, Table 1).
A similar result was observed when TBS ether of -chloroacetone oxime 3a was used as
nitrosoalkene precursor in the presence of K2CO3 (entry 9, Table 1). Quaternary salt 2a and TBS
3a did not produce the desired C-P adducts with Ph2P(O)H or (iPrO)2POH with Et3N (entries 5
and 8, Table 1) or without a base (entries 4 and 7, Table 1). When TBAF was used to generate
NSA from TBS ether 3a, 16 % yield of phosphonate 6a was obtained, however, the yield of
phosphine oxide 5a dropped to 49 % (entry 10, Table 1). Much better result was observed with
ene-nitrosoacetal 4a, which gave ca. 40 % of phosphonate 6a and 81 % of phosphine oxide 5a
(entry 11, Table 1). It is noteworthy, that no additives were needed in this reaction (vide infra).
With these promising results in hand we turned our attention toward optimizing the reaction of
diisopropyl phosphite with NSA precursor 4a by screening reaction conditions and reagents ratio
(Table 2).
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Table 2. Reaction of NSA precursor 4a with diisopropyl phosphite: an optimization study
(iPrO)2P(O)H
additive, solvent
HO
TMSO
Me
OTMS
N
O
P
temperature, time
N
Me
OiPr
then MeOH, 1 h
OiPr
6a
4a
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Entry Ratio
4a
Additive
Solvent
Temperature, Reaction Yield of 6a,
a,b
:
time, h
%
 C
6
7
8
9
(iPrO)2P(O)H
1 : 1
1
2
3
4
5
6
7
8
no
no
no
no
no
no
no
no
DMF
DMSO
MeCN
THF
24
24
24
24
24
24
24
24
38
25
18
9
0 С to rt
0 С to rt
0 С to rt
0 С to rt
0 С to rt
0 С to rt
0 С to rt
0 С to rt
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1 : 1
1 : 1
1 : 1
1 : 1
Et2O
traces
1 : 1
MeOH
H2O
0
1 : 1
0
1 : 1
urea/ChCl
(2 : 1)
22
9
1 : 1
no
CH2Cl2/DMF
(2 : 1)
24
20
0 С to rt
10
11
1 : 1
1 : 1
no
no
24
24
11
29
0 С to rt
0 С to rt
DBU (10 DMF
mol%)
12
13
1 : 1
1 : 1
NaH (100 THF
mol%)
-78 oC
24
24
0
Ti(OiPr)4
(10 mol%)
no
DMF
38
0 С to rt
14
15
1 : 1
DMF
DMF
50 oC
3
39
1 : 1.5
no
24
56b
0 С to rt
0 С to rt
-20 oC
16
17
1.5 : 1
1.5 : 1
no
no
DMF
DMF
24
24
65c
68c
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18
2 : 1
4 : 1
no
no
no
DMF
24
24
24
74c
82c
88c
0 С to rt
19
DMF
DMF
0 С to rt
0 С to rt
20
10 : 1
9
b
a
1
Yield was determined by H NMR with internal standard (trichloroethylene). Yield based on ene-nitrosoacetal
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b
4a. Yield based on diisopropyl phosphite. ChCl – choline chloride.
Changing DMF to other solvents as well as conducting reaction under solvent-free conditions
resulted in a considerable drop of the yield of Michael product 6a (entries 1-10, Table 2,
decomposition products of 4a were detected). No product was obtained in protic solvents (water
and methanol), which can themselves react with ene-nitrosoacetal 4a (entries 6 and 7, Table 2).
Deep eutectic solvent urea/ChCl, which was recently shown to be beneficial for reaction of NSA
with S-nucleophiles,6b was also less efficient compared to DMF (entry 8, Table 2). Additives of
bases to deprotonate (iPrO)2POH had no positive effect on the reaction outcome (entries 11 and
12, Table 2) as well as did not the addition of Ti(OiPr)4 (entry 13, Table 2), which is known to
promote reactions with diisopropyl phosphite.21 On the other hand, the yield of phosphonate 6a
substantially increased, when an excess of diisopropyl phosphite or NSA precursor 4a was used
(entries 15, 16 and 18-20, Table 2). Heating and cooling the reaction did not result in a
noticeable increase of the yield of the product 6a (entries 14 and 17, Table 2).
Based on these studies, ene-nitrosoacetals 4 were chosen as convenient NSA precursors to
explore substrate scope of Michael addition of P-nucleophiles (Scheme 3). Using the optimized
conditions (treatment of ene-nitrosoacetal 4 with a P-nucleophile in DMF), a series of ene-
nitrosoacetals 4 were tested in reactions with diphenylphosphine oxide (R = Ph) and diisopropyl
phosphite (R = OiPr). In most experiments, a 2-fold excess of ene-nitrosoacetals 4 was used to
ensure full conversion of the P-nucleophile.
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Scheme 3. Synthesis of phosphine oxides 5 and phosphonates 6 from ene-nitrosoacetals 4
4
5
6
7
8
HO
TMSO
OTMS
R2
O
P
DMF, rt, 24 h
N
O
P
N
R1
R
R1
H
R
then MeOH, 1 h
R
R
9
R2
5 6
10
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(1 equiv.)
Examples
4
(2 equiv.)
,
HO
HO
H
HO
N
O
P
N
O
N
O
P
P
Me
Ph
Ph
Ph
MeO2C
Ph
Ph
Ph
5c
HO
5a
, 88 %
, 81 %
5b
, 85 %
(74 % on 10 mmol scale)
HO
N
O
HO
N
O
P
N
O
P
P
EtO2C
Ph
Ph
Ph
5e
Ph
Ph
Ph
Ph
Ph
5f
, 95 %
, 92 %
5d
, 90 %
HO
HO
Me
N
O
P
HO
N
O
P
OiPr
N
O
P
Ph
Ph
OiPr
H
Ph
Ph
Me
6a
, 71 %
5h
, 33 %
5g
, 89 %
HO
HO
N
O
P
OiPr
HO
H
N
O
P
OiPr
N
O
P
Ph
OiPr
MeO2C
OiPr
OiPr
OiPr
6d
HO
, 59 %*
6b
, 63 %
6c
, 70 %
HO
Ph
HO
N
O
P
N
O
P
OiPr
N
O
P
Me
OiPr
EtO2C
6f
OiPr
OiPr
OiPr
OiPr
, 70 %
6i
, 0 %
6e
, 45 %*
Yields are given based on P-nucleophile. * 3 equiv. of corresponding NSA precursor 4 were used.
Diphenylphosphine oxide (R = Ph) reacted smoothly under these conditions with various ene-
nitrosoacetals 4a-h affording corresponding phosphine oxide adducts 5a-h in high yields
(Scheme 3). Importantly, even enamine 4b (R1,R2 = H), which is the precursor of highly unstable
nitrosoethylene, delivered the Michael adduct 5b in 85 % yield. Furthermore, the reaction could
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be scaled up to 10 mmol of diphenylphosphine oxide without noticeable decrease in the yield as
demonstrated by the synthesis of 2 grams of product 5a. Reactions with diisopropyl phosphite
proved to be more sensitive to the substitution in the NSA precursor. Enamines 4a-c,i with R1 =
H, Alk provided corresponding phosphonates 6a-c,i in good yields, while the phenyl substituted
substrate 4e gave adduct only in 28 % (the yield could be increased to 45 % with a 3-fold excess
of 4e). Also, we failed to achieve addition of diisopropyl phosphite to ene-nitrosoacetal 4f
bearing an electron withdrawing EtO2C-group (product 6f in Scheme 3). Most of oximes 5 and 6
were obtained as mixtures of E,Z-isomers, the ratio of which changes with time.22
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We then tested phoshines as nucleophiles in Michael addition to NSA nitrosoacetals 4 (Scheme
4). Our initial experiments with PH-phoshines were not successful. In reaction of model ene-
nitrosoacetal 4a with diphenyl phosphine only 9 % yield of corresponding adduct 7a was formed
(Scheme 4, eqn. (1)), and no Michael addition products were detected with PhPH2. Reaction of
ene-nitrosoacetal 4a with PPh3 afforded an indecipherable mixture of products (Scheme 4, eqn.
(2)). Fortunately, when triphenylphosphonium bromide was employed instead of PPh3,
quaternary -oximinoalkylphosphonium salt 8a was obtained in 80 % isolated yield (Scheme 4,
eqn. (3)).
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Scheme 4. Reactions of ene-nitrosoacetal 4a with Ph2PH and Ph3PH+Br-
4
5
6
7
Ph2PH, DMF
HO
Me
TMSO
Me
OTMS
N
Ph
P
N
0 C to rt, 24 h
(1)
Ph
then MeOH, 2 h
8
7a
, 9 %
9
4a
(2 equiv.)
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Ph3P, DMF
TMSO
Me
OTMS
N
0 C to rt, 24 h
complex mixture
of products
(2)
then MeOH, 2 h
4a
(2 equiv.)
Ph3PH Br , DMF
HO
TMSO
Me
OTMS
N
Ph
P
0 C to rt, 24 h
N
Br
Ph
(3)
Me
8a
then MeOH, 2 h
Ph
, 80 %
4a
(2 equiv.)
Having realized that quaternary phosphonium derivatives are more reactive towards NSA, we
examined diphenylphosphine-borane complex23 (Ph2PHBH3) as a nucleophile in reaction with
ene-nitrosoacetals 4 Indeed, the desired tertiary phosphine-borane complexes 9a,c,d were
produced in this reaction in good yields and could be isolated by column chromatography
(Scheme 5, eqn. (1)). Same reaction of 4a with phenylphosphine-borane complex afforded
bis(oxime)phophine derivative 10a in moderate yield (Scheme 5, eqn. (2)). Phosphine-borane
complexes 9 and 10 are remarkably stable at ambient conditions and do not suffer intramolecular
reduction of oxime group. Given the possibility of removing BH3 fragment using known
procedures,24 this transformation can be viewed as method for preparation of valuable tertiary -
oximinoalkylphosphines of type 7. As a demonstration of this, borane 9a was converted into free
phosphine 7a in 65 % yield upon the action of DABCO (Scheme 5, eqn. (3)).
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Scheme 5. Addition of phosphine-borane complexes to ene-nitrosoacetals 4
4
5
6
7
8
9
Ph
H P BH3
Ph
HO
TMSO
R
OTMS
N
BH3
P
DMF, 0 C to rt, 24 h
N
(1)
R
Ph
then MeOH, 2 h
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Ph
4a c d
, , (2 equiv.)
9a
9c
9d
, R = Me, 72 %
, R = (CH2)2CO2Me, 66 %
, R = Bn, 67 %
Ph
H P BH3
H
HO
R
OH
R
TMSO
OTMS
N
BH3
P
N
N
DMF, 0 C to rt, 24 h
(2)
then MeOH, 2 h
Me
Ph
10a
, 51 %
4a
(3 equiv.)
DABCO
HO
Me
HO
Me
N
Ph
P
N
BH3
P
toluene, 40 C, 24 h
(3)
Ph
Ph
Ph
7a
, 65 %
9a
The plausible mechanism involved in the reaction of ene-nitrosoacetals 4 with P-H nucleophiles
is depicted in Scheme 6. Blue color was observed in some reactions confirming the participation
of NSA as intermediates. The later are generated from enamines 4 upon the attack of a Lewis
base (LB) on the silicon atom followed by the fragmentation of heminitrosoacetal anion A. P-
nucleophile or even DMF can act as a Lewis base (dissolution of 4a in a pure DMF results in the
appearance of blue color (max = 738 nm) characteristic for NSA).5b,18a Subsequent Michael
addition of the deprotonated P-nucleophile to the transient NSA affords the corresponding -P-
substituted oxime.
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Scheme 6. Plausible mechanism for coupling of ene-nitrosoacetals 4 with P-H nucleophiles
4
5
6
TMSO
OTMS
TMSO
O
LB
N
N
TMSO
R1
7
8
9
R1
R2
R2
4
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- LB-TMS
A
O
N
R1
R2
NSA
LB - DMF or P-nucleophile
O
P
R
R
H
HO
O
N
O
N
O
P
R
P
P
O
R1
R
R1
R
R
R
R
R2
R2
P
R
R
O
5 6
,
TMSO
O
P
P
R
R
R
R
O
P
OH
R
R
H
Conclusions
In conclusion, Michael addition of P-nucleophiles taken in H-form (diphenylphosphine oxide,
diisopropyl phosphite, diphenylphosphine-borane complex and triphenylphosphonium bromide)
to highly reactive conjugated nitrosoalkenes has been achieved. Among four types of NSA
precursors tested, ene-nitrosoacetals 4 performed most efficient in these reactions. New methods
for the synthesis of valuable -oximinoalkyl-substituted phosphonates, phosphine oxides,
phosphine-borane complexes and phosphonium salts have been developed.
Experimental
All reactions were carried out in oven-dried (150°C) glassware. NMR spectra were recorded at
room temperature with residual solvents peaks as an internal standard. Multiplicities are
indicated by s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), m (multiplet), br
(broad). HRMS were measured on electrospray ionization (ESI) instrument with a time-of-flight
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(TOF) detector. Column chromatography was performed using silica gel 40-60 m 60A with
hexane/ethyl acetate mixtures as eluents. Analytical thin-layer chromatography was performed
on silica gel plates with QF-254. Visualization was accomplished with UV light and or solution
of anisaldehyde/H2SO4 in ethanol. CH2Cl2 and MeCN were distilled from CaH2, DMF was
distilled from CaH2 under reduced pressure. THF and Et2O were distilled from LiAlH4. Hexane,
petroleum ether, pentane, methanol and ethyl acetate were distilled without drying agents.
Diphenylphosphine oxide, diisopropyl phosphite, diphenyl phosphine, triphenyl phosphine,
phenyl phosphine (10 % soln in hexane) and BH3-SMe2 were commercial grade and were used
as received. Triphenylphosphonium bromide,25 quaternary triethylammonium salt 2a19 were
prepared using previously described protocols. Previously described ene-nitrosoacetals 4a,26
4b,26 4c,27 4d,28 4e,29 4f,27 4g26 and 4h26 were prepared from corresponding aliphatic nitro
compounds in accordance with literature procedures (for structures of 4 see Scheme S1 in the
Supporting Information).
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1-Сhloropropan-2-one O-(tert-butyldimethylsilyl) oxime (3a). To a stirred solution of
chloroacetone (0.73 mL, 0.85 g, 9.15 mmol) in CHCl3 (27 mL) were added molecular sieves 4Å
(1.7 g) followed by O-(tert-butyldimethylsilyl)hydroxylamine30 (2.70 g, 18.4 mmol) at rt under
argon atmosphere. The reaction was stirred for 24 h and additional portion of molecular sieves
4Å (1.7 g) was added and the mixture was kept for additional 120 h with occasional shaking.
Then, the solution was filtered off, concentrated in vacuum (40 Torr, 40 C), and the residue was
subjected to flash chromatography on silica gel (eluent  petroleum ether) to give 0.706 g (35 %
based on chloroacetone) of oxime ether 3a as a colorless volatile liquid. Rf = 0.74 (EtOAc–
hexane, 1:3). Mixture of E/Z isomers (ratio 6 : 1). 1H NMR (300 MHz, Chloroform-d, E-isomer)
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δ 4.12 (s, 2H), 2.00 (s, 3H), 0.95 (s, 9H), 0.19 (s, 6H). C{1H} NMR (75 MHz, Chloroform-d,
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E-isomer) δ 157.7, 46.3, 26.1, 18.2, 12.2, -5.2. H NMR (300 MHz, Chloroform-d, Z-isomer) δ
4.31 (s, 2H), 2.05 (s, 3H), 0.95 (s, 9H), 0.19 (s, 6H). HRMS: m/z [M+H]+ calcd. for
[C9H21ClNOSi]+: 222.1075 and 224.1046; found: 222.1076 and 224.1047.
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N-(But-1-en-2-yl)-O-(trimethylsilyl)-N-((trimethylsilyl)oxy)hydroxylamine (4i). Prepared by
silylation of 2-nitrobutane (1.9 g, 18.5 mmol) with TMSBr (5.4 mL, 40.6 mmol) and Et3N (5.9
mL, 42.4 mmol) using a procedure analogous to the synthesis of enamine 4c.26 Yield: 3.77 g (82
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1
%). Colorless liquid unstable at rt (stored in CH2Cl2 solution at -20 C). H NMR (300 MHz,
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Chloroform-d) δ 5.01 (m, 1H), 4.55 (m, 1H), 2.31 (q, J = 7.5 Hz, 2H), 1.09 (t, J = 7.5 Hz, 3H),
0.19 (s, 18H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d) δ 161.5 (C), 101.4 (CH2), 20.8
(CH2), 12.4 (CH3), 0.1 (6 CH3). 29Si{1H} NMR (59 MHz, Chloroform-d): δ = 24.3. HRMS: m/z
[M+Na]+ calcd. for [C10H25NO2Si2Na]+: 270.1316; found: 270.1316.
Procedure used for model experiments (Table 1, Table 2, entries 1, 11, 13): To a
corresponding NSA precursor (1a, 2a, 3a or 4a, 0.25 mmol for (iPrO)2POH, 0.5 mmol for
Ph2POH) were consequently added a solution of P-nucleophile (0.25 mmol) in DMF (0.4 mL)
and additive (Et3N – 1 equiv. per NSA precursor, K2CO3 – 0.5 equiv. per NSA precursor, TBAF
– 1 equiv. per NSA precursor, DBU – 0.1 equiv. per NSA precursor, Ti(OiPr)4 – 0.1 equiv. per
NSA precursor) at 0 C under argon atmosphere with vigorous stirring. Then, cooling bath was
removed and the resulting solution was allowed to stand for 24 h at rt with occasional shaking.
Methanol (ca. 2 mL) was added and the mixture was stirred for additional 1 h and then
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concentrated under reduced pressure (40 – 50 C). The residue was analyzed by H NMR with
internal standard (trichloroethylene). Results are summarized in Table 1.
Procedure used for model experiments (Table 2, entries 2-7, 10): To ene-nitrosoacetal 4a (58
mg, 0.25 mmol) was added corresponding solvent (0.75 mL) followed by (iPrO)2POH at 0 C
under argon atmosphere with vigorous stirring. Then, cooling bath was removed and the
resulting solution was allowed to stand for 24 h at rt with occasional shaking. Methanol (ca. 2
mL) was added and the mixture was stirred for additional 1 h and then concentrated under
1
reduced pressure (40 – 50 C). The residue was analyzed by H NMR with internal standard
(trichloroethylene). Results are summarized in Table 2.
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Procedure used for model experiments (Table 2, entries 14-20): To a ene-nitrosoacetal 4a (58
mg, 0.25 mmol) was added a solution of (iPrO)2POH (amount specified in Table 2) in DMF (0.4
mL for entries 14-18; 1 mL for entry 19; 2.5 mL for entry 20) at rt (for entry 14), 0 C (for
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entries 15, 16, 18-20), -20 C (for entry 17) under argon atmosphere with vigorous stirring. The
reaction was kept at the temperature specified in Table 2 for the indicated period of time.
Methanol (ca. 2 mL) was added and the mixture was stirred for additional 1 h and then
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concentrated under reduced pressure (40 – 50 C). The residue was analyzed by H NMR with
internal standard (trichloroethylene). Results are summarized in Table 2.
General procedure for the addition of P-nucleophiles to ene-nitrosoacetals 4. A stock 1 M
solution of ene-nitrosoacetal in CH2Cl2 (2 mL, 2 mmol) was placed in Schlenk tube and solvent
was evaporated in vacuum. To the residue, a solution of a P-nucleophile (1 mmol, if not stated
otherwise) in DMF (1.6 mL) was added at 0 C under argon atmosphere with vigorous stirring.
Then, cooling bath was removed and the resulting solution was allowed to stand for 24 h at rt
with occasional shaking. Methanol (ca. 5 mL) was added and the mixture was stirred for
additional 1 h and then concentrated under reduced pressure (40 – 50 C). The residue was
subjected to a column chromatography on silica gel (for compounds 5a-h; 6a-e,i) or
crystallization (for compound 8a) to give the desired product.
(2-(Hydroxyimino)propyl)diphenylphosphine oxide (5a). Prepared according to general
procedure from 101 mg of diphenylphosphine oxide (0.5 mmol) and 233 mg of enamine 4a (1.0
mmol). Yield: 111 mg (81 % based on Ph2POH). White crystals. Mp 187 – 189 °C (pentane–
Et2O) (lit.15c 190 – 191 °C, lit.14 188 – 190 °C). Rf = 0.14 (EtOAc). Dynamic mixture of E/Z
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isomers (ratio 9 : 1, changes to ca. 1.5 : 1 upon standing). H NMR (300 MHz, DMSO-d6, E-
isomer) δ 10.63 – 10.61 (br, 1H), 7.93 – 7.72 (m, 4H), 7.65 – 7.39 (m, 6H), 3.46 (d, J = 13.8 Hz,
2H), 1.79 (d, J = 2.4 Hz, 3H). 13C{1H} NMR (75 MHz, DEPT135, DMSO-d6, E-isomer) δ 149.0
(d, J = 8.7 Hz, C), 133.7 (d, J = 97.9 Hz, 2 C), 131.6 (d, J = 2.1 Hz, 2 CH), 130.6 (d, J = 9.4 Hz,
4 CH), 128.5 (d, J = 11.6 Hz, 4 CH), 36.7 (d, J = 67.1 Hz, CH2), 15.2 (CH3). 31P{1H} NMR (121
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MHz, DMSO-d6, E-isomer) δ 27.49. H NMR (300 MHz, DMSO-d6, Z-isomer, characteristic
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5
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signals) δ 10.61 – 10.60 (br, 1H), 3.66 (d, J = 14.9 Hz, 2H), 1.82 (d, J = 2.3 Hz, 3H). C{1H}
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7
NMR (75 MHz, DEPT135, DMSO-d6, Z-isomer, characteristic signals) δ 130.4 (d, J = 10.2 Hz,
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4 CH), 21.1 (CH3). P{1H} NMR (121 MHz, DMSO-d6, Z-isomer) δ 26.60. FTIR (KBr): 3150
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(s), 3059 (s), 2857 (s, sh), 1652 (w), 1589 (w), 1437 (s, sh), 1369 (m, sh), 1264 (m), 1173 (s),
1144 (s), 1120 (s), 1005 (m), 962 (s), 816 (m), 750 (s), 720 (s), 695 (s), 573 (m). HRMS: m/z
[M+H]+ calcd. for [C15H17NO2P]+: 274.0991; found: 274.0986.
Scale-up synthesis of 5a. A stock 1 M solution of ene-nitrosoacetal 4a in CH2Cl2 (20 mL, 20
mmol) was placed in Schlenk flask and solvent was evaporated in vacuum. To the residue, a
cooled (0 – 5 C) solution of diphenylphosphine oxide (10 mmol) in DMF (16 mL) was added
dropwise at 0 C under argon atmosphere with vigorous stirring. The mixture was slowly
allowed to warm to rt and then kept overnight with occasional shaking. Methanol (ca. 30 mL)
was added and the mixture was stirred for additional 1 h. Then, the solution was concentrated
under reduced pressure to remove volatiles and DMF (40 – 50 C) and dried in vacuum (0.2
Torr). The resulting white gummy solid was triturated with ethyl acetate several times, filtered
and dried in vacuum until constant weight to give 1.81 g (66 %) of pure 5a. Mother liquors were
concentrated under reduced pressure and the residue was subjected to a column chromatography
on silica gel to give additional 0.22 g (8 %) of 5a. Overall yield: 2.03 g (74 %).
2-(Diphenylphosphoryl)acetaldehyde oxime (5b). Prepared according to general procedure
from 152 mg of diphenylphosphine oxide (0.75 mmol) and 329 mg of enamine 4b (1.5 mmol).
Yield: 164 mg (85 % based on Ph2POH). White crystals. Mp 158 – 161 °C (pentane–Et2O). Rf =
0.17 (EtOAc). Dynamic mixture of E/Z isomers (ratio 9 : 1). 1H NMR (300 MHz, DMSO-d6, E-
isomer) δ 10.88 (br s, 1H), 7.81 (dd, J = 10.9, 8.5 Hz, 4H), 7.62 – 7.47 (m, 6H), 7.23 (q, J = 6.5
Hz, 1H), 3.50 (dd, J = 14.2, 6.5 Hz, 2H). 13C{1H} NMR (75 MHz, DEPT135, DMSO-d6, E-
isomer) δ 141.4 (dd, J = 8.3, 3.5 Hz, C), 133.2 (d, J = 98.4 Hz, 2 C-P), 131.8 (d, J = 2.8 Hz, 2
CH), 130.6 (d, J = 9.4 Hz, 4 CH), 128.7 (d, J = 11.7 Hz, 4 CH), 31.2 (d, J = 68.0 Hz, CH2).
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31P{1H} NMR (121.49 MHz, DMSO-d6, E-isomer) δ = 27.91. 1H NMR (300 MHz, DMSO-d6, Z-
isomer, characteristic signals) δ 11.33 (br s, 1H), 6.70 (q, J = 5.8 Hz, 2H), 3.64 (dd, J = 14.4, 5.8
Hz, 4H). 31P{1H} NMR (121.49 MHz, DMSO-d6, Z-isomer) δ = 27.62. HRMS: m/z [M+H]+
calcd. for [C14H15NO2P]+: 260.0835; found: 260.0832. Anal. Calcd. for C14H14NO2P: C, 64.86
%; H, 5.44 %; N, 5.40 %. Found: C , 64.72 %; H, 5.47 %; N, 5.50 %.
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Methyl 5-(diphenylphosphoryl)-4-(hydroxyimino)pentanoate (5c). Prepared according to
general procedure from 101 mg of diphenylphosphine oxide (0.5 mmol) and 305 mg of enamine
4a (1.0 mmol). Yield: 152 mg (88 % based on Ph2POH). Oil which solidified upon standing. Mp
1
50 – 54 °C. Rf = 0.25 (EtOAc). Dynamic mixture of E/Z isomers (ratio 9 : 1). H NMR (300
MHz, DMSO-d6, E-isomer) δ 10.77 (s, 1H), 7.90 – 7.72 (m, 4H), 7.64 – 7.43 (m, 6H), 3.58 (s,
3H), 3.52 (d, J = 13.8 Hz, 2H), 2.55 (s, 4H). 13C{1H} NMR (75 MHz, DEPT135, DMSO-d6, E-
isomer) δ 172.7 (C), 151.1 (C), 133.6 (d, J = 97.4 Hz, 2 C), 131.6 (d, J = 2.4 Hz, 2 CH), 130.6
(d, J = 9.4 Hz, 4 CH), 128.5 (d, J = 11.6 Hz, 4 CH), 51.3 (CH3), 35.2 (d, J = 67.3 Hz, CH2), 28.7
(CH2), 24.4 (CH2). 31P{1H} NMR (121 MHz, DMSO-d6, E-isomer) δ 27.91. 1H NMR (300 MHz,
31
DMSO-d6, Z-isomer, characteristic signals) δ 10.91 (s, 1H), 3.67 (d, J = 15.1 Hz, 2H). P{1H}
NMR (121 MHz, DMSO-d6, Z-isomer) δ 26.69. HRMS: m/z [M+H]+ calcd. for [C18H21NO4P]+:
346.1203; found: 346.1193.
(2-(Hydroxyimino)-3-phenylpropyl)diphenylphosphine oxide (5d). Prepared according to
general procedure from 51 mg of diphenylphosphine oxide (0.25 mmol) and 155 mg of enamine
4d (0.5 mmol). Yield: 78 mg (90 % based on Ph2POH). White crystals. Mp 128 – 131 °C
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(pentane–Et2O). R = 0.36 (EtOAc). Dynamic mixture of E/Z isomers (ratio 1.4 : 1). H NMR
f
(300 MHz, Chloroform-d, E-isomer) δ 10.1 – 8.3 (br, 1H), 7.77 – 7.68 (m, 4H), 7.55 – 7.33 (m,
6H), 7.29 – 7.18 (m, 5H), 3.87 (s, 2H), 3.20 (d, J = 13.6 Hz, 2H). 13C{1H} NMR (75 MHz,
DEPT135, Chloroform-d, E-isomer) δ 152.0 (d, J = 8.8 Hz, C), 136.4 (C), 132.3 (d, J = 100.7
Hz, 2 C), 131.9 (d, J = 2.8 Hz, 2 CH), 131.0 (d, J = 9.4 Hz, 4 CH), 129.5 (2 CH), 128.7 (2 CH),
128.6 (d, J = 6.1 Hz, 4 CH), 126.5 (CH), 35.0 (d, J = 67.7 Hz, CH2), 34.3 (CH2). 31P{1H} NMR
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(121 MHz, Chloroform-d) δ 30.42. H NMR (300 MHz, Chloroform-d, Z-isomer) δ 10.1 – 8.3
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(br, 1H), 7.88 – 7.78 (m, 4H), 7.55 – 7.33 (m, 6H), 7.29 – 7.18 (m, 5H), 3.66 (d, J = 1.9 Hz, 2H),
3.51 (d, J = 14.9 Hz, 2H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, Z-isomer,
characteristic signals) δ 151.6 (d, J = 8.8 Hz, C), 136.8 (C), 130.9 (d, J = 9.0 Hz, 4 CH), 129.5 (2
CH), 126.6 (CH), 40.9 (CH2), 29.2 (d, J = 65.2 Hz, CH2). 31P{1H} NMR (121.49 MHz,
Chloroform-d) δ = 29.92. FTIR (KBr): 3184 (m, br), 3060 (m, sh), 2879 (m, br), 1968 (w, sh),
1897 (w, sh), 1813 (w, sh), 1720 (w, sh), 1638 (w, sh), 1591 (w, sh), 1494 (m), 1453 (m), 1437
(s), 1390 (w), 1333 (w, sh), 1262 (m), 1184 (s), 1120 (s), 1100 (m), 1073 (w), 1029 (w), 976 (s),
836 (m), 734 (s, sh), 717 (s), 694 (s), 619 (w), 593 (m), 560 (m), 536 (s), 508 (s, sh), 412 (w, sh).
HRMS: m/z [M+H]+ calcd. for [C21H21NO2P]+: 350.1304; found: 350.1303.
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(2-(Hydroxyimino)-2-phenylethyl)diphenylphosphine oxide (5e). Prepared according to
general procedure from 101 mg of diphenylphosphine oxide (0.5 mmol) and 295 mg of enamine
4e (1.0 mmol). Yield: 155 mg (92 % based on Ph2POH). White crystals. Mp 155 –158 °C
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(pentane–Et2O). Rf = 0.31 (EtOAc). Dynamic mixture of E/Z isomers (ratio 1.2 : 1). H NMR
(300 MHz, DMSO-d6, E-isomer) δ 10.93 (br s, 1H), 7.83 – 7.69 (m, 4H), 7.55 – 7.38 (m, 6H),
7.25 (m, 5H), 3.83 (d, J = 13.6 Hz, 2H). 13C{1H} NMR (75 MHz, DEPT135, DMSO-d6, E-
isomer, characteristic signals) δ 148.5 (d, J = 10.0 Hz, C), 133.9 (d, J = 98.4 Hz, 2 C), 131.4 (d, J
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= 1.9 Hz, 2 CH), 130.6 (d, J = 9.2 Hz, 4 CH), 36.4 (d, J = 67.3 Hz, CH2). P{1H} NMR (121
MHz, DMSO-d6, E-isomer) δ 27.04. 1H NMR (300 MHz, DMSO-d6, Z-isomer) δ 11.49 (s, 1H),
7.83 – 7.69 (m, 4H), 7.67 – 7.58 (m, 2H), 7.55 – 7.38 (m, 6H), 7.25 (m, 3H), 4.11 (d, J = 15.4
Hz, 4H). 13C{1H} NMR (75 MHz, DEPT135, DMSO-d6, Z-isomer, characteristic signals) δ
134.0 (d, J = 98.8 Hz, 2 C), 131.6 (d, J = 2.2 Hz, 2 CH), 130.5 (d, J = 9.5 Hz, 4 CH), 29.0 (d, J =
64.3 Hz, CH2). 31P{1H} NMR (121 MHz, DMSO-d6, Z-isomer) δ 26.00. 13C{1H} NMR (75
MHz, DMSO-d6, signals of both isomers): δ 135.8 (C), 133.8 (C), 128.6 (CH), 128.4 (d, J = 11.6
Hz, 4 CH), 128.3 (CH), 128.2 (2 CH), 127.9 (2 CH), 127.4 (2 CH), 126.4 (2 CH). HRMS: m/z
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[M+H]+ calcd. for [C20H19NO2P]+: 336.1148; found: 336.1148. Anal. Calcd. for C20H18NO2P: C,
71.63 %; H, 5.41 %; N, 4.18 %. Found: C, 71.13 %; H, 5.06 %; N, 4.20 %.
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Ethyl 3-(diphenylphosphoryl)-2-(hydroxyimino)propanoate (5f). Prepared according to
general procedure from 76 mg of diphenylphosphine oxide (0.38 mmol) and 218 mg of enamine
4f (0.75 mmol). Yield: 118 mg (89 % based on Ph2POH). White solid. Mp 142 – 145 °C
(pentane–Et2O) (lit.13b 152 – 153 °C). Rf = 0.19 (EtOAc). Single isomer with E-configuration. 1H
NMR (300 MHz, Chloroform-d) δ 12.91 (s, 1H), 7.90 – 7.78 (m, 4H), 7.57 – 7.37 (m, 6H), 4.06
(q, J = 7.1 Hz, 2H), 3.93 (d, J = 14.9 Hz, 2H), 1.14 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (75 MHz,
DEPT135, Chloroform-d) δ 163.9 (C), 142.9 (d, J = 9.6 Hz, C), 132.1 (d, J = 2.5 Hz, 2 CH),
132.0 (d, J = 102.3 Hz, 2 C), 131.3 (d, J = 9.8 Hz, 4 CH), 128.6 (d, J = 12.3 Hz, 4 CH), 61.7
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(CH2), 28.7 (d, J = 64.7 Hz, CH2), 14.1 (CH3). P{1H} NMR (121.49 MHz, Chloroform-d) δ =
30.09. HRMS: m/z [M+H]+ calcd. for [C17H19NO4P]+: 332.1046; found: 332.1049. NMR spectra
are in agreement with literature data.13b
2-(Diphenylphosphoryl)propanal oxime (5g). Prepared according to general procedure from
101 mg of diphenylphosphine oxide (0.5 mmol) and 233 mg of enamine 4g (1.0 mmol). Yield:
122 mg (89 % based on Ph2POH). White crystals. Mp 157 – 159 °C (pentane–Et2O). Rf = 0.22
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(EtOAc). Dynamic mixture of E/Z isomers (ratio 1.1 : 1). H NMR (300 MHz, COSY, HSQC,
Chloroform-d, E-isomer) δ 11.01 – 9.47 (br, 1H, OH), 7.92 – 7.66 (m, 4H, o-C6H4), 7.56 – 7.28
(m, 7H, m,p-C6H5 and =CH), 3.58 – 3.37 (m, 1H, CH-P), 1.30 (dd, J = 15.6, 7.0 Hz, 3H, CH3).
13C{1H} NMR (75 MHz, DEPT135, HSQC, Chloroform-d, E-isomer, characteristic signals) δ
147.4 (С), 36.3 (d, J = 69.1 Hz, CH2), 11.4 (d, J = 3.8 Hz, CH3). 1H NMR (300 MHz, DMSO-d6,
E-isomer) δ 10.89 (br s, 1H, OH), 7.96 – 7.71 (m, 4H, o-C6H4), 7.69 – 7.38 (m, 6H, m,p-C6H5),
7.17 (dd, J = 6.7, 4.4 Hz, 1H, =CH), 4.00 – 3.75 (m, 1H, CH-P), 1.17 (dd, J = 15.3, 7.1 Hz, 3H,
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CH3). H NMR (300 MHz, COSY, HSQC, Chloroform-d, Z-isomer) δ 11.01 – 9.47 (br, 1H,
OH), 7.92 – 7.66 (m, 4H, o-C6H4), 7.56 – 7.28 (m, 6H, m,p-C6H5), 6.84 (dd, J = 8.6, 4.6 Hz, 1H),
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4.49 – 4.32 (m, 1H), 1.27 (dd, J = 15.9, 7.1 Hz, 3H, CH3). C{1H} NMR (75 MHz, DEPT135,
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HSQC, Chloroform-d, Z-isomer, characteristic signals) δ 146.7 (C), 30.2 (d, J = 69.6 Hz, CH2),
11.0 (d, J = 4.9 Hz, CH3). 1H NMR (300 MHz, DMSO-d6, Z-isomer) δ 11.30 (s, 1H, OH), 7.97 –
7.72 (m, 4H, o-C6H4), 7.67 – 7.41 (m, 6H, m,p-C6H5), 6.67 (dd, J = 8.5, 4.6 Hz, 1H, =CH), 4.47
– 4.30 (m, 1H, CH-P), 1.12 (dd, J = 14.8, 6.8 Hz, 3H, CH3). 13C{1H} NMR (75 MHz,
Chloroform-d, signals of both isomers): δ 132.4 – 131.9 (m, 2 p-C6H5), 131.2 (d, J = 99.8 Hz),
131.1 (d, J = 98.4 Hz), 131.0 (d, J = 98.2 Hz), 130.3 (d, J = 98.8 Hz) (2 C-P), 131.6 (d, J = 9.0
Hz), 131.3 (d, J = 9.2 Hz), 131.14 (d, J = 9.1 Hz), 131.10 (d, J = 9.4 Hz), 128.83 (d, J = 11.8
Hz), 128.78 (d, J = 11.7 Hz), 128.5 (d, J = 11.6 Hz) (8 o,m-C6H5). 31P{1H} NMR (121.49 MHz,
Chloroform-d, both isomers) δ = 32.34 and 32.06. HRMS: m/z [M+H]+ calcd. for
[C15H17NO2P]+: 274.0991; found: 274.0993.
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2-(Diphenylphosphoryl)cyclohexanone oxime (5h). Prepared according to general procedure
from 202 mg of diphenylphosphine oxide (1 mmol) and 546 mg of enamine 4h (2.0 mmol).
Yield: 100 mg (32 % based on Ph2POH). White crystals. Mp 79 – 83 °C (pentane–Et2O). Rf =
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0.35 (EtOAc). Dynamic mixture of E/Z isomers (ratio 1.1 : 1). H NMR (300 MHz, HSQC,
DMSO-d6) δ 10.55 – 10.52 and 10.52 – 10.48 (2 br, 1H and 1H, OH, both isomers), 7.97 – 7.69
and 7.65 – 7.34 (2 m, 8H and 12 H, o,m,p-C6H5, both isomers), 4.60 – 4.47 (m, 1H, CH-P, Z-
isomer), 3.79 – 3.65 (m, 1H, CH-P, E-isomer), 2.97 – 2.82 and 2.62 – 2.50 (2 m, 1 H and 1 H,
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both isomers), 2.38 – 1.10 (m, 14H). C{1H} NMR (75 MHz, HSQC, DMSO-d6) δ 154.1 and
153.1 (2 m, 2 C=N, both isomers), 133.4 (d, J = 96.5 Hz), 133.2 (d, J = 93.2 Hz), 133.1 (d, J =
96.7 Hz) and 132.8 (d, J = 94.3 Hz) (4 C of C6H5, both isomers), 131.7 (d, J = 2.0 Hz), 131.5 (d,
J = 2.5 Hz), 131.4 (d, J = 1.6 Hz) and 131.1 (d, J = 1.6 Hz) (4 CH of C6H5, both isomers), 130.9,
130.8, 130.7 and 130.6 (m, 8 CH of C6H5, both isomers), 128.8 (d, J = 11.0 Hz), 128.6 (d, J =
11.2 Hz), 128.2 (d, J = 11.0 Hz) and 127.9 (d, J = 11.6 Hz) (8 CH of C6H5, both isomers), 40.1
(CH-P, E-isomer, overlapped with DMSO-d5), 33.7 (d, J = 65.5 Hz, CH-P, Z-isomer), 30.8, 27.0,
26.9, 26.6 (d, J = 3.8 Hz), 25.0, 23.4 and 22.6 (d, J = 3.2 Hz), 22.1 (8 CH2, both isomers).
31P{1H} NMR (121 MHz, DMSO-d6) δ 32.83 and 32.07 (both isomers). NMR spectra are in
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agreement with literature data.31 HRMS: m/z [M+H]+ calcd. for [C18H21NO2P]+: 314.1304;
found: 314.1302.
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Diisopropyl (2-(hydroxyimino)propyl)phosphonate (6a). Prepared according to general
procedure from 83 mg of diisopropyl phosphite (0.5 mmol) and 233 mg of enamine 4a (1.0
mmol). Yield: 84 mg (71 % based on (iPrO)2POH). Oil. Rf = 0.24 (EtOAc). Dynamic mixture of
E/Z isomers (ratio 9 : 1, changes to 1.5 : 1 upon standing). 1H NMR (300 MHz, Chloroform-d, E-
isomer) δ 9.8  8.9 (br s, 1H), 4.68 (m, 2H), 2.71 (d, J = 21.9 Hz, 2H), 1.96 (d, J = 2.1 Hz, 3H),
1.27 (m, 12H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-isomer) δ 150.8 (d, J = 9.2
Hz, C), 71.1 (d, J = 6.7 Hz, 2 CH), 35.1 (d, J = 140.4 Hz, CH2), 24.1 (d, J = 3.9 Hz, 2 CH3), 24.0
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(d, J = 4.9 Hz, 2 CH3), 14.6 (d, J = 1.4 Hz, CH3). P{1H} NMR (121 MHz, Chloroform-d, E-
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isomer) δ 23.53. H NMR (300 MHz, Chloroform-d, Z-isomer) δ 9.8  8.9 (br s, 1H), 4.68 (m,
2H), 3.01 (d, J = 23.5 Hz, 2H), 1.87 (s, 3H), 1.27 (m, 12H). 13C{1H} NMR (75 MHz, DEPT135,
Chloroform-d, Z-isomer, characteristic signals) δ 28.25 (d, J = 138.1 Hz, CH2), 20.84 (s, CH3).
31P{1H} NMR (121 MHz, Chloroform-d, Z-isomer) δ 22.36. NMR spectra are in accordance
with literature data.32 HRMS: m/z [M+H]+ calcd. for [C9H21NO4P]+: 238.1204; found: 238.1203.
Diisopropyl (2-(hydroxyimino)ethyl)phosphonate (6b). Prepared according to general
procedure from 166 mg of diisopropyl phosphite (1.0 mmol) and 438 mg of enamine 4a (2.0
mmol). Yield: 141 mg (63 % based on (iPrO)2POH). Oil unstable at rt. Rf = 0.29 (EtOAc).
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Dynamic mixture of E/Z isomers (ratio 4 : 1). H NMR (300 MHz, Chloroform-d, E-isomer) δ
9.02 (br m, 1H), 7.38 (q, J = 6.4 Hz, 1H), 4.71 (m, 2H), 2.73 (dd, J = 21.7, 6.5 Hz, 2H), 1.30 (d,
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J = 6.0 Hz, 12H). C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-isomer) δ 143.2 (d, J =
8.8 Hz, C), 71.4 (d, J = 6.6 Hz, 2 CH), 29.4 (d, J = 142.2 Hz, CH2), 24.1 (d, J = 4.1 Hz, 2 CH3),
24.1 (d, J = 4.1 Hz, 2 CH3). 31P{1H} NMR (121 MHz, Chloroform-d, E-isomer) δ 23.17 (d, J =
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11.1 Hz). H NMR (300 MHz, Chloroform-d, Z-isomer) δ 9.45 (br m, 1H), 6.78 (q, J = 5.8 Hz,
1H), 4.71 (m, 2H), 2.99 (dd, J = 21.6, 5.9 Hz, 2H), 1.30 (d, J = 6.0 Hz, 12H). 31P{1H} NMR (121
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MHz, Chloroform-d, Z-isomer) δ 22.45 (d, J = 12.4 Hz). NMR spectra are in accordance with
literature data.33 HRMS: m/z [M+Na]+ calcd. for [C8H18NO4PNa]+: 246.0872; found: 246.0866.
Methyl 5-(diisopropoxyphosphoryl)-4-(hydroxyimino)pentanoate (6c). Prepared according to
general procedure from 165 mg of diisopropyl phosphite (1.0 mmol) and 610 mg of enamine 4c
(2.0 mmol). Yield: 216 mg (70 % based on (iPrO)2POH). Oil. Rf = 0.27 (EtOAc). Dynamic
mixture of E/Z isomers (ratio 25 : 1). 1H NMR (300 MHz, Chloroform-d, E-isomer) δ 8.84 (br s,
1H), 4.82 – 4.65 (m, 2H), 3.68 (s, 3H), 2.81 (d, J = 21.9 Hz, 2H), 2.76 – 2.59 (m, 4H), 1.33 (d, J
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= 6.1 Hz, 6H), 1.31 (d, J = 6.1 Hz, 6H). C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-
isomer) δ 173.2 (C), 152.8 (d, J = 9.9 Hz, C), 71.1 (d, J = 6.6 Hz, 2 CH), 51.7 (CH3), 33.8 (d, J =
140.3 Hz, CH2), 29.6 (CH2), 24.1 (d, J = 1.5 Hz, CH2), 24.0 (d, J = 3.9 Hz, 2 CH3), 23.9 (d, J =
5.0 Hz, 2 CH3). 31P{1H} NMR (121.49 MHz, CDCl3, E-isomer) δ = 23.43. 1H NMR (300 MHz,
Chloroform-d, Z-isomer, characteristic signals) δ 9.25 – 9.13 (br, 1H), 2.98 (d, J = 21.8 Hz, 2H).
31P{1H} NMR (121 MHz, Chloroform-d, Z-isomer) δ 22.9. FTIR (thin layer): 3241 (s), 3093
(m), 2981 (s), 2935 (s), 1739 (s), 1439 (m), 1387 (m, sh), 1224 (s, sh), 1177 (s), 1105 (m), 993
(s), 892 (w), 758 (w), 610 (w). HRMS: m/z [M+H]+ calcd. for [C12H25NO6P]+: 310.1413; found:
310.1414.
Diisopropyl (2-(hydroxyimino)-3-phenylpropyl)phosphonate (6d). Prepared according to
general procedure from 83 mg of diisopropyl phosphite (0.5 mmol) and 464 mg of enamine 4d
(1.5 mmol). Yield: 92 mg (59 % based on (iPrO)2POH). Oil. Rf = 0.46 (EtOAc). Dynamic
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mixture of E/Z isomers (ratio 15 : 1). H NMR (300 MHz, Chloroform-d, E-isomer) δ 9.86 –
9.44 (br m, 1H), 7.40 – 7.11 (m, 5H), 4.84 – 4.67 (m, 2H), 3.96 (s, 2H), 2.67 (d, J = 21.7 Hz,
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2H), 1.34 (d, J = 6.1 Hz, 6H), 1.32 (d, J = 6.1 Hz, 6H). C{1H} NMR (75 MHz, DEPT135,
Chloroform-d, E-isomer) δ 152.1 (d, J = 9.6 Hz, C), 136.4 (C), 129.4 (2 CH), 128.7 (2 CH),
126.6 (CH), 71.1 (d, J = 6.9 Hz, 2 CH), 33.6 (d, J = 1.9 Hz, CH2), 32.3 (d, J = 141.2 Hz, CH2),
24.1 (d, J = 3.8 Hz, 2 CH3), 24.0 (d, J = 4.9 Hz, 2 CH3). 31P{1H} NMR (121 MHz, Chloroform-
d, E-isomer) δ 23.70. 1H NMR (300 MHz, Chloroform-d, Z-isomer, characteristic signals) δ 3.72
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(d, J = 2.4 Hz, 2H), 2.96 (d, J = 23.7 Hz, 2H). 31P{1H} NMR (121 MHz, Chloroform-d, Z-
isomer) δ 22.4. FTIR (KBr): 3239 (s, br), 3065 (s, sh), 2980 (s), 2930 (s), 2246 (w), 1726 (m),
1650 (m), 1602 (m), 1495 (m), 1454 (m), 1376 (m), 1237 (s, sh), 1144 (m), 1104 (m), 993 (s, br),
911 (m), 861 (w), 734 (s), 702 (m), 647 (w), 601 (w), 550 (w), 479 (w). HRMS: m/z [M+H]+
calcd. for [C15H25NO4P]+: 314.1516; found: 314.1518.
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Diisopropyl (2-(hydroxyimino)-2-phenylethyl)phosphonate (6e). Prepared according to
general procedure from 83 mg of diisopropyl phosphite (0.5 mmol) and 443 mg of enamine 4e
(1.5 mmol). Yield: 67 mg (45 % based on (iPrO)2POH). Oil. Rf = 0.22 and 0.34 (2 isomers,
EtOAc). Dynamic mixture of E/Z isomers (ratio 22 : 1, changes to 3 : 1 upon standing). 1H NMR
(300 MHz, Chloroform-d, E-isomer) δ 9.55  9.35 (br s, 1H), 7.52 (d, J = 6.5 Hz, 2H), 7.42 –
7.28 (m, 3H), 4.63 (m, 2H), 3.10 (d, J = 21.5 Hz, 2H), 1.20 (d, J = 6.2 Hz, 6H), 1.14 (d, J = 6.2
Hz, 6H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-isomer) δ 150.0 (d, J = 10.0 Hz,
C), 133.3 (C), 129.0 (CH), 128.5 (2 CH), 128.0 (2 CH), 71.0 (d, J = 6.9 Hz, 2 CH), 34.7 (d, J =
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141.7 Hz, CH2), 24.1 (d, J = 3.7 Hz, 2 CH3), 23.8 (d, J = 5.2 Hz, 2 CH3). P{1H} NMR (121
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MHz, Chloroform-d, E-isomer) δ 23.35. H NMR (300 MHz, Chloroform-d, Z-isomer,
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characteristic signals) δ 3.50 (d, J = 23.5 Hz, 1H). P{1H} NMR (121 MHz, Chloroform-d, Z-
isomer) δ 22.1. HRMS: m/z [M+H]+ calcd. for [C14H23NO4P]+: 300.1359; found: 300.1358.
Diisopropyl (2-(hydroxyimino)butyl)phosphonate (6i). Prepared according to general
procedure from 165 mg of diisopropyl phosphite (1.0 mmol) and 494 mg of enamine 4i (2.0
mmol). Yield: 216 mg (70 % based on (iPrO)2POH). Oil. Rf = 0.29 (EtOAc). Dynamic mixture of
E/Z isomers (ratio 15 : 1, changes to ca. 1 : 1 upon standing). 1H NMR (300 MHz, Chloroform-d,
E-isomer) δ 9.95 – 8.86 (br, 1H), 4.76 – 4.60 (m, 2H), 2.69 (d, J = 21.9 Hz, 2H), 2.47 (q, J = 7.0
Hz, 2H), 1.27 (s, 12H), 1.05 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (75 MHz, DEPT135,
Chloroform-d, E-isomer) δ 155.2 (d, J = 6.9 Hz, C), 71.0 (d, J = 6.8 Hz, 2 CH), 32.7 (d, J =
141.3 Hz, CH2), 24.1 (d, J = 3.8 Hz, 2 CH3), 24.0 (d, J = 5.0 Hz, 2 CH3), 21.5 (d, J = 1.7 Hz,
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CH2), 9.9 (CH3). 31P{1H} NMR (121.49 MHz, Chloroform-d, E-isomer) δ = 23.68. H NMR
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(300 MHz, Chloroform-d, Z-isomer, characteristic signals) δ 3.01 (d, J = 23.6 Hz, 2H), 2.41 –
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2.33 (m, 2H). P{1H} NMR (121 MHz, Chloroform-d, Z-isomer) δ 22.49. HRMS: m/z [M+H]+
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1-(Diphenylphosphino)propan-2-one oxime (7a). In a Schlenk tube was placed 1 mL of 1 M
solution of ene-nitrosoacetal 4a (233 mg, 1 mmol) in CH2Cl2 and solvent was evaporated in
vacuum. To the residue, a solution of diphenyl phosphine (0.26 mL, 1.5 mmol) in DMF (1.6 mL)
was added at 0 C under argon atmosphere. Then, cooling bath was removed and the resulting
solution was allowed to stand for 24 h at rt with occasional shaking. Methanol (ca. 5 mL) was
added and the mixture was stirred for additional 1 h and then concentrated under reduced
pressure (40 – 50 C). The residue was subjected to a column chromatography on silica gel to
give 22 mg (9 % based on 4a) of phosphine 7a as white crystals. Mp 97 – 101 °C. Rf = 0.38
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(EtOAc–hexane, 1:1). Dynamic mixture of E/Z isomers (ratio 20 : 1). H NMR (300 MHz,
Chloroform-d, E-isomer) δ 8.65 – 7.55 (br, 1H), 7.47 – 7.39 (m, 4H), 7.36 – 7.29 (m, 6H), 3.00
(d, J = 1.4 Hz, 2H), 1.97 (s, 3H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-isomer) δ
155.6 (d, J = 8.3 Hz, C), 137.9 (d, J = 13.7 Hz, 2 C-P), 132.9 (d, J = 19.2 Hz, 4 CH), 129.0 (2
CH), 128.6 (d, J = 6.9 Hz, 4 CH), 36.8 (d, J = 16.0 Hz, CH2), 14.9 (d, J = 6.2 Hz, CH3). 31P{1H}
NMR (121.49 MHz, Chloroform-d, E-isomer) δ = -19.63. 1H NMR (300 MHz, Chloroform-d, Z-
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isomer, characteristic signals) δ 3.22 (d, J = 2.0 Hz, 2H), 1.73 (s, 3H). P{1H} NMR (121.49
MHz, Chloroform-d, Z-isomer) δ = -16.18. HRMS: m/z [M+H]+ calcd. for [C15H17NOP]+:
258.1048; found: 258.1071.
(2-(Hydroxyimino)propyl)triphenylphosphonium bromide (8a). In a Schlenk tube was placed
1 mL of 1 M solution of ene-nitrosoacetal 4a (233 mg, 1 mmol) in CH2Cl2 and solvent was
evaporated in vacuum. To the residue, a solution of triphenylphosphonium bromide (214 mg, 80
% purity, 0.5 mmol) in DMF (0.8 mL) was added at 0 C under argon atmosphere. Then, cooling
bath was removed and the resulting solution was allowed to stand for 24 h at rt with occasional
shaking. Methanol (ca. 5 mL) was added and the mixture was stirred for additional 1 h and then
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concentrated under reduced pressure (40 – 50 C). The residue was treated with water (ca. 3
mL), the precipitate was filtered off, washed with diethyl ether and dried to give 91 mg of salt
8a. Second crystallization from mother liquor gave addition 74 mg of 8a. Yield: 165 mg (80 %
based on triphenylphosphonium bromide). White crystals. Mp 195 – 199 °C (H2O). Single
isomer with unknown configuration. 1H NMR (300 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.94 – 7.62
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(m, 15H), 4.94 (d, J = 14.4 Hz, 2H), 1.82 (s, 3H). C{1H} NMR (75 MHz, DEPT135, DMSO-
d6) δ 147.6 (d, J = 9.1 Hz, C), 134.4 (d, J = 3.1 Hz, 3 CH), 133.7 (d, J = 10.4 Hz, 6 CH), 129.8
(d, J = 12.7 Hz, 6 CH), 119.7 (d, J = 88.0 Hz, 3 C-P), 28.4 (d, J = 54.6 Hz, CH2), 15.1 (d, J = 8.0
Hz, CH3). 31P{1H} NMR (121.49 MHz, DMSO-d6) δ = 22.32. FTIR (KBr): 3490 (m), 3422 (w),
3134 (s, br), 3060 (s), 2901 (m), 2866 (m), 2207 (w), 2034 (w), 1727 (w, sh), 1663 (w, sh), 1586
(m), 1482 (m), 1436 (s), 1369 (m), 1340 (m), 1315 (m, sh), 1183 (w, sh), 1107 (s), 997 (m, sh),
971 (m), 846 (w), 814 (m), 776 (w), 750 (s), 715 (s), 687 (s), 615 (w), 511 (s, sh), 491 (s), 442
(m). HRMS: m/z [M-Br]+ calcd. for [C21H21NOP]+: 334.1355; found: 334.1359.
General procedure for the addition of Ph2PHBH3 complex to N,N-bis(oxy)enamines 4.
Preparation of diphenylphosphine-borane complex:34 in a Schlenk tube with anhydrous THF
(3.5 mL) was added Ph2PH (304 L, 1.75 mmol) followed by Me2SBH3 (166 L, 1.75 mmol)
complex at 0 C under argon atmosphere. The mixture was stirred for 1 h to give a 0.5 M
solution of Ph2PHBH3 complex in THF (1H NMR spectrum matched with literature data35).
Reaction with enamines 4: 1.5 mL of the obtained 0.5 M solution of Ph2PHBH3 in THF was
mixed with DMF (1.2 mL). The resulting solution was added to ene-nitrosoacetal 4 (1.5 mmol)
at 0 C under argon atmosphere. Then, cooling bath was removed and the resulting solution was
allowed to stand for 24 h at rt with occasional shaking. Methanol (ca. 5 mL) was added and the
mixture was stirred for additional 1 h and then concentrated under reduced pressure (40 – 50 C).
The residue was subjected to column chromatography on silica gel to give Michael adduct 9.
1-(Diphenylphosphino)propan-2-one oxime borane complex (9a). Prepared according to
general procedure from 1.5 mL of 0.5 M solution of Ph2PHBH3 (0.75 mmol) in THF and 350
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mg of enamine 4a (1.5 mmol). Yield: 146 mg (72 % based on phosphine complex). Oil. Rf = 0.5
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(EtOAc–hexane, 1:1). Dynamic mixture of E/Z isomers (ratio 1.7 : 1). H NMR (300 MHz,
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(d, J = 12.5 Hz, 2H), 1.90 (d, J = 2.3 Hz, 3H), 1.67 – 0.50 (m, 3H). C{1H} NMR (75 MHz,
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DEPT135, Chloroform-d, E-isomer) δ 152.4 (d, J = 4.4 Hz, C), 132.4 (d, J = 9.4 Hz, 4 CH),
131.5 (2 CH), 128.9 (d, J = 9.9 Hz, 4 CH), 128.4 (d, J = 66.9 Hz, 2 C), 34.2 (d, J = 33.0 Hz,
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CH2), 15.8 (CH3). H NMR (300 MHz, Chloroform-d, Z-isomer) δ 8.62 – 8.08 (br, 1H), 7.84 –
7.65 (m, 4H), 7.56 – 7.39 (m, 6H), 3.51 (d, J = 13.4 Hz, 2H), 1.89 (d, J = 1.9 Hz, 3H), 1.67 –
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0.50 (m, 3H). C{1H} NMR (75 MHz, DEPT135, Chloroform-d, Z-isomer) δ 151.2 (d, J = 4.1
Hz, C), 132.4 (d, J = 9.8 Hz, 4 CH), 131.5 (2 CH), 129.0 (d, J = 54.6 Hz, 2 C), 128.8 (d, J = 9.8
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Hz, 4 CH), 27.2 (d, J = 31.9 Hz, CH2), 21.5 (CH3). P{1H} NMR (121 MHz, Chloroform-d,
both isomers) δ 15.05 (br m). 11B{1H} NMR (96 MHz, Chloroform-d, both isomers) δ -36.38 – -
40.64 (br m). HRMS: m/z [M+H]+ calcd. for [C15H20BNOP]+: 272.1373; found: 272.1369; m/z
[M-H]+ calcd. for [C15H18BNOP]+: 270.1216; found: 270.1213.
Methyl 5-(diphenylphosphanyl)-4-(hydroxyimino)pentanoate borane complex (9c).
Prepared according to general procedure from 2 mL of 0.5 M solution of Ph2PHBH3 (1 mmol)
in THF and 610 mg of enamine 4c (2 mmol). Yield: 226 mg (66 % based on phosphine
complex). Oil. Rf = 0.45 (EtOAc–hexane, 1:1). Dynamic mixture of E/Z isomers (ratio 2.6 : 1).
1H NMR (300 MHz, Chloroform-d, E-isomer) δ 8.66 – 7.93 (br, 1H), 7.83 – 7.64 (m, 4H), 7.57 –
7.37 (m, 6H), 3.66 (s, 3H), 3.35 (d, J = 12.5 Hz, 2H), 2.65 – 2.52 (m, 4H), 1.70 – 0.46 (m, 3H).
13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-isomer) δ 173.3 (C), 154.2 (d, J = 4.4 Hz,
C), 132.4 (d, J = 9.4 Hz, 4 CH), 131.5 (d, J = 2.8 Hz, 2 CH), 128.9 (d, J = 9.9 Hz, 4 CH), 128.6
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(d, J = 55 Hz, 2 C), 51.8 (CH3), 32.8 (d, J = 33.0 Hz, CH2), 29.8 (CH2), 25.1 (CH2). H NMR
(300 MHz, Chloroform-d, Z-isomer) δ 8.66 – 7.93 (br, 1H), 7.83 – 7.64 (m, 4H), 7.57 – 7.37 (m,
6H), 3.61 (s, 3H), 3.50 (d, J = 13.3 Hz, 2H), 2.65 – 2.52 (m, 2H), 2.47 (t, J = 7.0 Hz, 2H), 1.70 –
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0.46 (m, 3H). C{1H} NMR (75 MHz, DEPT135, Chloroform-d, Z-isomer) δ 173.1 (C), 152.2
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(d, J = 4.8 Hz, C), 132.4 (d, J = 9.4 Hz, 4 CH), 131.5 (d, J = 2.8 Hz, 2 CH), 129.0 (d, J = 55 Hz,
2 C), 128.7 (d, J = 9.4 Hz, 4 CH), 51.7 (CH3), 30.2 (CH2), 30.1 (CH2), 26.5 (d, J = 31.9 Hz,
CH2). 31P{1H} NMR (121 MHz, Chloroform-d, both isomers) δ 16.46 – 14.28 (m). 11B{1H}
NMR (96 MHz, Chloroform-d) δ -35.16 – -41.17 (m). FTIR (KBr): 3418 (br, s), 3060 (s, sh),
2952 (s, sh), 2388 (s, sh), 2260 (m), 1644 (m), 1485 (m), 1437 (s), 1361 (m), 1311 (s), 1258 (s,
sh), 1200 (s), 1173 (s), 1108 (s), 1062 (s), 1028 (m), 965 (s), 906 (m, sh), 839 (m), 738 (s), 694
(s), 593 (m), 497 (m), 471 (m), 434 (m). HRMS: m/z [M+Na]+ calcd. for [C18H23BNO3PNa]+:
366.1406; found: 366.1404; m/z [M-H]+ calcd. for [C18H22BNO3P]+: 342.1430; found: 342.1437.
1-(Diphenylphosphanyl)-3-phenylpropan-2-one oxime borane complex (9d). Prepared
according to general procedure from 1.5 mL of 0.5 M solution of Ph2PHBH3 (0.75 mmol) in
THF and 464 mg of enamine 4d (1.5 mmol). Yield: 174 mg (67 % based on phosphine
complex). Oil. Rf = 0.63 (EtOAc–hexane, 1:1). E-isomer, which isomerizes upon standing in
solution to give 2.3 : 1 mixture of E/Z isomers. 1H NMR (300 MHz, Chloroform-d, E-isomer) δ
7.85 – 7.62 (m, 4H), 7.59 – 7.38 (m, 6H), 7.37 – 7.09 (m, 6H), 3.85 (s, 2H), 3.15 (d, J = 12.4 Hz,
2H), 1.84 – 0.48 (m, 3H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, E-isomer) δ 153.8
(d, J = 3.9 Hz, C), 136.0 (C), 132.4 (d, J = 9.4 Hz, 4 CH), 131.5 (d, J = 2.2 Hz, 2 C), 129.3 (2
CH), 128.9 (d, J = 9.9 Hz, 4 CH), 128.7 (2 CH), 128.6 (d, J = 55.2 Hz, 2 C), 126.7 (CH), 34.2
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(CH2), 31.0 (d, J = 32.5 Hz, CH2). H NMR (300 MHz, Chloroform-d, Z-isomer, characteristic
signals) δ 3.62 (s, 2H), 3.38 (d, J = 13.4 Hz, 2H). 31P{1H} NMR (121 MHz, Chloroform-d, both
isomers) δ 15.41 (br m). 11B{1H} NMR (96 MHz, Chloroform-d, both isomers) δ -35.74 – -40.90
(br m). HRMS: m/z [M+Na]+ calcd. for [C21H23BNOPNa]+: 370.1506; found: 370.1502; m/z [M-
H]+ calcd. for [C21H22BNOP]+: 346.1530; found: 346.1525.
1,1'-(Phenylphosphanediyl)bis(propan-2-one) dioxime borane complex (10a). Preparation of
phenylphosphine-borane complex: in a Schlenk tube with anhydrous THF (2 mL) was added a
solution of PhPH2 in hexane (1.6 mL, 1.0 mmol) followed by Me2SBH3 (0.095 mL, 1.0 mmol)
complex at 0 C under argon atmosphere. The mixture was stirred for 1 h to give a solution of
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PhPH2BH3 complex (1H NMR spectrum matched with literature data35). Reaction with enamine
4a: 2.8 mL of the obtained solution of PhPH2BH3 (0.75 mmol) was mixed with DMF (1.2 mL).
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The resulting solution was added to ene-nitrosoacetal 4a (699 mg, 3.0 mmol) at 0 C under argon
atmosphere. Then, cooling bath was removed and the resulting solution was allowed to stand for
24 h at rt with occasional shaking. Methanol (ca. 5 mL) was added and the mixture was stirred
for additional 1 h and then concentrated under reduced pressure (40 – 50 C). The residue was
subjected to column chromatography on silica gel to give 102 mg (51 % based on phosphine
complex) of Michael adduct 10a as colorless oil. Rf = 0.38 (EtOAc–hexane, 1:1). Dynamic
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mixture of isomers. H NMR (300 MHz, Chloroform-d, all isomers) δ 8.98 – 8.07 (br, 2H, 2
OH), 7.94 – 7.70 (m, 2H), 7.60 – 7.40 (m, 3H), 3.41 – 2.89 (m, 4H), 1.84 (s, 6H), 1.49 – 0.41 (m,
3H). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, signals of E-fragments) δ 152.7 (d, J =
5.0 Hz, 2 C), 152.5 (d, J = 5.7 Hz, 2 C), 34.0 (d, J = 31.4 Hz, 2 CH2), 33.1 (d, J = 31.4 Hz, 2
CH2), 16.0 (2 CH3), 15.8 (2 CH3). 13C{1H} NMR (75 MHz, DEPT135, Chloroform-d, signals of
Z-fragments) δ 151.5 (d, J = 6.0 Hz, 2 C), 151.4 (d, J = 5.3 Hz, 2C), 27.8 (d, J = 30.0 Hz, 2
CH2), 27.5 (d, J = 30.3 Hz, 2 CH2), 21.6 (2 CH3), 21.5 (2 CH3). Other signals: 132.5 (d, J = 9.4
Hz, 2 CH), 132.1 (CH), 128.94 (d, J = 9.8 Hz) and 128.88 (d, J = 10.1 Hz) (2 CH), 127.1 (d, J =
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50.6 Hz, C), 126.6 (d, J = 51.4 Hz, C). P{1H} NMR (121 MHz, Chloroform-d, all isomers) δ
16.21 – 12.13 (br m). 11B{1H} NMR (96 MHz, Chloroform-d, all isomers) δ -36.09 – -42.11 (br
m). FTIR (KBr): 3241 (s br, OH), 2920 (m), 2400 (s), 1654 (m), 1438 (m), 1400 (m), 1373 (m),
1275 (s), 1112 (s), 1020 (m), 820 (s), 882 (m), 749 (s), 610 (s). HRMS: m/z [M+H]+ calcd. for
[C12H21BN2O2P]+: 267.1430; found: 267.1433; m/z [M-H]+ [C12H19BN2O2P]+: 265.1274; found:
265.1277.
Conversion of borane complex 9a into free phosphine 7a. To a solution of phosphine-borane
complex 9a (113 mg, 0.42 mmol) in toluene (0.5 mL) was added DABCO (50 mg, 0.45 mmol)
under argon atmosphere. The mixture was stirred at 40 C for 24 h (within 3 days), and then
concentrated in vacuum. The residue was subjected to a column chromatography on silica gel
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