Synthesis of chiral β-aminophosphine oxides via novel azaboretidinium bromide salts

Article abstract of DOI:10.1039/a703936k

The enamino(triphenyl)phosphonium salts [Ph₃PCH=CMeNR¹R²]⁺ Br^- [where R¹ = R² = (CH₂)₄, (CH₂)₅; (S)-CHMePh; R¹ = H, R² = (S)-CHMePh; R¹ = H, R² = (S)-(CH₂)₃-CH(CH₂OH)] have been synthesised and have been shown to react with an excess of borane-tetrahydrofuran to give novel azaboretidinium salts - the first examples of four-membered C-B-N-C heterocycles. The structure of [(1S,3R,4S,1'S)-4-methyl-1-(1-phenylethyl)-1,2-azaboretidin-1-ium-2-uid-3-yl] triphenylphosphonium bromide has been established by X-ray crystallography. Borane does not result in any significant stereoselectivity in these reductions and the azaboretidinium salts are mixtures of diastereomers. In contrast, the similar reduction with (R)-(+)-monoisopinocampheylborane or (S)-(-)-monoisopinocampheylborane leads to single diastereomers in high yields when R¹ and R² are non-bulky; with sterically demanding groups the azaboretidinium salts are unstable and decompose on work-up. Heating these azaboretidinium salts with aqueous sodium hydroxide in methanol, or better, aqueous sodium hydroxide alone, results in the direct formation of the phosphine oxides, Ph₂P(O)CH₂CHMeNR¹R² which, in the case of compounds derived from IpC₂BH₂, have an ee value of >75%. In some cases, particularly when R¹ and R² are bulky, the use of sodium hydroxide in methanol results in an appreciable amount of rac-Ph₂PCH₂CHMe(OMe) as a by-product, but this can be avoided by carrying out the reactions in the absence of methanol.

Full text of DOI:10.1039/a703936k

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Synthesis of chiral â-aminophosphine oxides via novel
azaboretidinium bromide salts1
Brian L. Booth,* Nicholas J. Lawrence and Humayan S. Rashid
Department of Chemistry, UMIST, PO Box 88, Manchester, UK M60 1QD
The enamino(triphenyl)phosphonium salts [Ph PCH᎐CMeNR1R2]ϩ BrϪ [where R1 = R2 = (CH ) , (CH ) ;
᎐
3
2
4
2 5
|
|
(S)-CHMePh; R1 = H, R2 = (S)-CHMePh; R1 = H, R2 = (S)-(CH2)3-CH(CH2OH)] have been synthesised
and have been shown to react with an excess of boraneؒtetrahydrofuran to give novel azaboretidinium
salts—the first examples of four-membered C᎐B᎐N᎐C heterocycles. The structure of [(1S,3R,4S,1ЈS)-4-
methyl-1-(1-phenylethyl)-1,2-azaboretidin-1-ium-2-uid-3-yl]triphenylphosphonium bromide has been
established by X-ray crystallography. Borane does not result in any significant stereoselectivity in these
reductions and the azaboretidinium salts are mixtures of diastereomers. In contrast, the similar reduction
with (R)-(ϩ)-monoisopinocampheylborane or (S)-(Ϫ)-monoisopinocampheylborane leads to single
diastereomers in high yields when R1 and R2 are non-bulky; with sterically demanding groups the
azaboretidinium salts are unstable and decompose on work-up. Heating these azaboretidinium salts with
aqueous sodium hydroxide in methanol, or better, aqueous sodium hydroxide alone, results in the direct
formation of the phosphine oxides, Ph2P(O)CH2CHMeNR1R2 which, in the case of compounds derived
from Ipc2BH2, have an ee value of >75%. In some cases, particularly when R1 and R2 are bulky, the use of
sodium hydroxide in methanol results in an appreciable amount of rac-Ph2PCH2CHMe(OMe) as a
by-product, but this can be avoided by carrying out the reactions in the absence of methanol.
Although several methods are described in the literature for
the synthesis of P–N ligands2–8 there are very few reported
examples of chiral P–N compounds.9–15 Transition metal com-
plexes of chiral P–N ligands have recently found application as
catalysts for asymmetric hydrogenation,9 hydrosilylation of
carbonyl compounds,10 palladium-assisted substitution of allyl
acetates11 and conjugate addition of nucleophiles to α,β-
unsaturated carbonyl compounds.12
Compound 2 is easily prepared in good yield (70%) by
reaction between triphenylphosphine and prop-2-ynyl bromide
with hydrogen bromide (48% aq.) in dioxane.21 The known
reaction between 2 and piperidine22 and the new reactions with
pyrrolidine, (S)-(Ϫ)-1-phenylethylamine, (S)-(ϩ)-pyrrolidine-2-
methanol and (S,S)-N,N-bis(1-phenylethyl)amine were carried
out by refluxing the reactants in acetonitrile to give the expected
salts 1a–e (Scheme 1) in the yields shown in Table 1. In each
case the progress of reaction was conveniently followed by 31P
NMR spectroscopy and most of the products were isolated
analytically pure without the need for recrystallisation. The
physical and spectroscopic data for these compounds are given
in Tables 1–3.† Similar reactions, including the reaction with
(R)-(ϩ)-1-phenylethylamine, have recently been reported by
Palacios et al.23
Previous work carried out in our Department suggested the
possibility that chiral β-aminophosphorus ligands may be con-
veniently prepared from enamino(triphenyl)phosphonium salts
of the type [Ph PCR1᎐CR2NR3R4]ϩ XϪ 1 by reduction of the
᎐
3
double bond and modification of the triphenylphosphonium
group. We have shown that trifluoromethanesulfonate (triflate)
salts of type 1 (where R1 = alkyl, aryl or CO2R; R2 = alkyl or
aryl; R3 = H; R4 = Me, X = OSO2CF3) are available from the
reactions of N-methylnitrilium triflate salts with triphenyl-
phosphoranes16,17 or, for R1 = H, with trimethylsilylmethyl-
idenetriphenylphosphorane.18 Compounds where R1 = H, R2 =
Me and X = Br are more conveniently prepared by the method
of Schweizer and co-workers19,20 from the reactions of primary
or secondary amines with triphenyl(prop-2-ynyl)phosphonium
bromide 2.
We now describe the borane reduction of a number of enam-
ino(triphenyl)phosphonium salts and the conversion of some
of the novel azaboretidinium salts produced into enantiomeri-
cally pure β-aminodiphenylphosphine oxides with potential
application as ligands for asymmetric catalysis.
An interesting observation from the 13C NMR spectrum of
1a is that the four C atoms of the pyrrolidine ring (C1Ј and C2Ј)
are non-equivalent. The C1Ј and C2Ј carbon atoms of the
piperidine ring in 1b are broadened suggesting non-equivalence
in this compound also. The source of this non-equivalence is
likely to be restricted rotation around the C2᎐N bond. This is
most clearly shown for the compound 1d which exists as two
rotamers in a 1:2 ratio as demonstrated by the two sets of
bands present in the 1H, 13C and 31P NMR spectra (see Tables 2
and 3). We have not established the structure of the major
rotamer, but it is expected to be 1dY (where R1 = C1ЈH2,
R2 = C4ЈHCH2OH) rather than 1dZ (see Scheme 1) as in the
latter there will be considerable steric interaction between the
CH2OH group and the methyl substituent C3. It is known from
X-ray crystallographic studies17 that enamino(triphenyl)phos-
phonium salts of type 1 have the E-configuration with the PPh3
group anti to the amino substituent. It has also been established
that in the solid state and, presumably, also in solution the
nitrogen lone pair electrons are extensively delocalised so that
the molecule exists predominantly in the zwitterion form shown
in Scheme 1. This strengthens the C2᎐N bond resulting in
Results and discussion
Our initial efforts were directed towards the synthesis of enam-
ino(triphenyl)phosphonium salts of type 1 having a chiral
group on the nitrogen atom, in the expectation that this might
be used to exert stereocontrol in the reduction step. The syn-
thesis from nitrilium triflate salts was clearly not suitable for
this purpose, but Schweizer’s route from 2 could easily be
adapted by suitable choice of a chiral primary or secondary
amine, although the compounds available by this route are
restricted to those where R1 = H and R2 = Me.
† The numbering in the NMR assignments and the discussion is as
shown on the structures. The names in the Experimental section are
given with the systematic IUPAC numbering systems.
J. Chem. Soc., Perkin Trans. 1, 1997
3509

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Table 1 Physical data for enaminophosphonium salts 1a–e
Found (calc.) (%)
Comp.
1a
Yield (%)
Mp (ЊC)
230–231
232–233
251–252
197–198
79–80
Molecular formula
C25H27BrNP
C
H
N
Br
17.5
(17.7)
17.1
(17.2)
16.2
(15.9)
16.6
P
m/z, [(Mϩ Ϫ Br)]
90
75
76
78
88
66.1
(66.4)
66.7
(66.9)
69.4
(69.3)
64.9
(64.6)
73.1
(73.3)
6.1
(6.0)
6.4
(6.2)
6.1
(5.8)
6.0
(6.3)
6.1
(6.1)
3.2
(3.1)
3.0
(3.0)
3.0
(2.8)
2.9
(3.0)
2.4
(2.3)
6.7
(6.8)
6.6
(6.6)
5.9
(6.2)
6.4
372
386
422
402
526
1b
C26H29BrNP
1c
C29H29BrNP
1d
C31H33BrNOP
C37H37BrNP
(15.9)
13.2
(13.2)
(6.2)
1e
showed that a clean reaction occurred over 3 h to give a single
product, and after work-up a pale-yellow oil was isolated in
84% yield. It quickly became apparent from the spectroscopic
evidence that this compound was not the expected reduction
product, (Ph3PCH2CHMeNHCHMePh)ϩ BrϪ. Mass spec-
trometry showed the presence of boron, which was confirmed
by 11B NMR spectroscopy, and the 1H, 13C and 31P NMR
spectra indicated that it was an approximate 1:1 mixture of two
diastereomers. Fortunately, it proved possible to separate these
by recrystallisation from propan-2-ol and good crystals were
obtained of the diastereomer 4cA which was insoluble in
propan-2-ol; the soluble diastereomer 4cB was isolated as a
slightly impure pale-yellow oil. The single crystal X-ray struc-
ture of 4cA established that it was a novel azaboretidinium salt
having the 1S,3R,4S,1ЈS-configuration (see ref. 1). The mole-
cule is associated with half a molecule of propan-2-ol in the
unit cell.‡
The similar reduction of the compounds 1a,b,d and e using a
large excess of BH3ؒTHF in dichloromethane gave the analo-
gous products 4a,b,d and e. The compounds rac-4a and rac-4b,
which have a novel spiro structure, were obtained in good
isolated yields as a racemic mixture in a clean reaction with no
by-products. The reaction of 1d (as a 2:1 mixture of rotamers)
gave, in addition to the diastereomers rac-4dA and rac-4dB,
appreciable amounts of the decomposition products 5 and 6
(see Scheme 2).
Analysis of the product mixtures from the reaction of 1c and
1d showed no evidence that the chiral substituents on the nitro-
gen atom exert any stereocontrol in these reduction reactions
as the diastereomeric products appear to be formed in an
approximate 1:1 ratio in both cases. The salt 1e derived from
the C2-symmetric amine [(S)-CHMePh]2NH25 similarly gave a
1:1 ratio of the diastereomers rac-4eA and rac-4eB upon reduc-
tion. In this last reaction the products 4eA and 4eB were
obtained in very poor overall yield and the major products in
this reaction were the decomposition products 5 and 7. This
implies that when the substituents on the nitrogen atom are
bulky, as in 1d and 1e, the azaboretidinium salts obtained upon
hydroboration are unstable and dissociate readily on work-up.
The physical and spectroscopic data for the compounds rac-4a,
4b, 4cA, 4cB, 4dA, 4dB and 4eA plus 4eB are shown in Tables
4–6. In the case of compounds 4c and 4d the diastereomers
could be separated, but this was not possible in the case of
compound 4e as there was so little compound available.
As the presence of a chiral group on the nitrogen atom of 1 is
insufficient to affect the facial selectivity using a simple borane
complex for the hydroboration, an alternative strategy was to
use a more bulky, chiral borane derivative in the hope that this
would be selective. Attempts to use the bulky achiral borane
Ha
+
X
+
Ph3P
(i)
m
1
2
o
R1R2NH
Br–
3
i
p
PPh2 CH3
H
Br–
2
1a–e
R2
R1
+
+
H
+
N
H
N
R1
–
R2
–
+
CH3
Ph3P
CH3
Ph3P
Z
Y
1′
2′
3′
N
1a X =
1b X =
1c X =
CH3
N
4′
1′
R
2′
CH3
+
3′
N
Ph3P
H
4′
4′
5′
H3C 2′
5′
1′
3′
6′
S
CH3
NH
+
R
N
–
CH3
+
1′
2′
3′
Ph3P
H
N
1d X =
1e X =
4′
3 R = H or CO2Me
S
CH2OH
H
5′
Me
S
Ph
6′
3'
N
1'
5′
S
4′
2′
CH3
Scheme 1 Reagents and conditions: (i) acetonitrile, reflux 1–2 h
restricted rotation around this bond with the possibility of hav-
ing the rotamers Y and Z. A similar observation has been made
previously by Bestmann et al.,24 who showed that for the com-
pound 3 the two N᎐CH3 groups had distinctly different chem-
ical shift values at room temperature. The rotational energy
does depend upon the group bonded to the C1 atom and for the
compounds 3 (R = Me, Et or Prn) only a single methyl signal is
seen in each case.24
Attempts to hydrogenate the salt 1a using 10% palladium on
charcoal as a catalyst in methanol gave only unchanged starting
material after a week at room temperature and 1 atm hydrogen.
The zwitterionic character of 1a–e suggested the possibility that
an electrophilic reducing agent, such as borane, may be more
appropriate for this reduction. Consequently, the reduction of
1c was explored using an excess of BH3ؒTHF in THF solvent
at room temperature. Monitoring by 31P NMR spectroscopy
‡ The crystallographic data for this compound are reported in ref. 1 and
atomic coordinates, bond lengths and angles, and thermal parameters
have been deposited at the Cambridge Crystallographic Data Centre.
See Information for Authors, ref. 1, Issue 1.
3510
J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 1H and 31P chemical shifts for β-enaminophosphonium salts 1a–ea
b
Comp.
1a
δP
δH (J/Hz)
ϩ16.1
ϩ16.1
ϩ15.8
1.85 (s, 3H, H3), 2.05 (m, 4H, H3Ј and H2Ј), 3.40 (t, 2H, 3JH᎐H 6.2, H1Ј or H4Ј), 3.55 (d, 1H, 2JP᎐H 14.6, H1), 3.60 (t, 2H,
3JH᎐H 6.2, H4Ј or H1Ј) and 7.55–7.75 (m, 15H, Ph3P)
1b
1.60 (br s, 6H, H2Ј, H3Ј and H4Ј), 1.80 (s, 3H, H3), 3.45 (br s, 4H, H1Ј and H5Ј), 3.85 (d, 1H, 2JP᎐H 14.1, H1) and 7.45–7.70
(m, 15H, Ph3P)
1c
1.75 (d, 3H, 3JH᎐H 6.8, H2Ј), 1.90 (s, 3H, H3), 3.50 (d, 1H, 2JP᎐H 14.0, H1), 4.55 [apparent quintet (overlapping d of q), 1H,
3JH᎐H 6.8, 3JNH᎐H 4.2, H1], 7.20–7.90 (m, 20H, Ph3P᎐ and Ph) and 9.10 (apparent br t, 1H, 3JNH᎐H 4.2, NH)
1.85 (s, 6H, H3), 1.90 (m, 1H, H3Јa), 1.95 (m, 4H, H2Ј), 2.05 (s, 6H, H3), 2.20 (m, 1H, H3Јb), 3.40 (m, 2H, H1Јa), 3.50–3.65
(m, 2H, H1Јb), 3.60 (d, 2H, 2JP᎐H 14.5, H1), 3.75–3.85 (m, 1H, H5Јa), 4.15–4.30 (m, 1H, H5Јb and H4Ј), 5.10 (t, 1H, 3JH᎐H
6.5, OH), 5.20 (t, 1H, 3JH᎐H 6.5, OH) and 7.55–7.75 (m, 30H, Ph3P)
1d
ϩ16.2
ϩ16.6
1e
ϩ15.8
1.90 (d, 6H, 3JH᎐H 7.1, H2Ј), 2.15 (s, 3H, H3), 3.60 (d, 1H, 2JP᎐H 13.4, H1), 5.25 (br m, 2H, H1Ј), 7.10–7.35 (m, 10H, Ph)
and 7.55–7.75 (m, 15H, Ph3P)
a All spectra were determined in CDCl3. b 85% H3PO4 as external reference.
Table 3 13C chemical shifts and 31P–13C coupling constants for β-enaminophosphonium salts 1a–e
δC(CDCl3) [J(31P᎐13C)/Hz]
Comp.
1
2
3
1Ј
2Ј
i
o
m
p
Other bands
1a
57.5
[122.1]
162.5
[13.7]
22.0
[6.2]
49.0
[0.0]
49.1
[0.0]
48.5
[0.0]
br.
24.4
[0.0]
25.0
[0.0]
25.5
[0.0]
br.
123.5
[92.0]
132.5
[10.6]
130.0
[12.6]
133.5
[3.1]
1b
59.5
[121.5]
163.6
[13.7]
22.4
[6.3]
123.5
[91.2]
133.0
[10.3]
130.5
[12.6]
134.0
[2.1]
23.5 (C3Ј)
[0.0]
55.1
[0.0]
[0.0]
23.6
[0.0]
1c
1d
58.5
[122.0]
165.1
[13.7]
22.0
[6.2]
123.1
[91.0]
132.7
[10.4]
129.7
[12.5]
133.7
[2.8]
143.4 (C3Ј),
126.1 (C4Ј),
128.6 (C5Ј)
22.1 and 23.1
(C3Ј), 61.8
and 61.9
57.2
[121.7]
59.7
162.6
[13.9]
163.5
[13.9]
22.5
[5.9]
49.1
[br.]
50.0
[br.]
27.1
[0.0]
27.8
[0.0]
123.1
[91.4]
123.3
[91.3]
132.8
[9.9]
132.9
[9.8]
129.9
[12.4]
133.5
[2.6]
[122.2]
(C4Ј), 62.6 br.
(C5Ј)
1e
66.0
[118.7]
161.0
[11.8]
23.5
[7.3]
56.1
[br.]
17.5
[0.0]
122.5
[91.5]
132.5
[10.3]
130.0
[12.6]
133.9
[3.0]
138.9 (C3Ј),
128.7 (C4Ј),
127.8 (C5Ј),
132.4 (C6Ј)
Table 4 Physical data for the azaboretidinium bromide salts 4a–e and 8aA, 8bA and 8cA
Found (calc.) (%)
Comp.
4a
Yield (%)
Mp (ЊC)
159–160
154–155
236–237
225–226
173–174
159–160
Oil
Molecular formula
C25H30BBrNPؒ0.5H2O
C35H46BBrNP
C
H
N
Br
P
m/z, [(Mϩ Ϫ Br)]
89
91
78
95
30
86
38
28
22
2.5
63.2
(62.9)
68.2
(67.8)
63.8
(63.8)
71.0
(70.1)
66.6
(66.3)
72.1
(71.8)
68.6
(67.4)
62.5
6.5
(6.1)
8.8
(8.0)
7.1
(6.8)
8.5
(7.8)
6.6
(6.3)
7.8
(7.4)
6.8
(6.2)
6.4
2.9
(3.1)
2.0
(2.3)
2.7
(2.9)
2.0
(2.3)
2.7
(2.7)
2.0
(2.1)
3.1
(2.7)
2.9
16.8
(17.0)
6.5
(6.8)
386
522
401
536
436
572
436
416
416
541
8aA
4b
C26H33BBrNPؒ0.5H2O
C36H48BBrNP
16.0
(16.3)
6.3
(6.3)
8bA
4cA
C29H32BBrNPؒ0.5H2O
C39H48BBrNP
14.9
(15.2)
5.6
(5.9)
8cA
4cB
C29H32BBrNP
16.1
(15.5)
16.0
(16.1)
15.9
6.2
(6.0)
4dA
Foam
C26H32BBrNOP
C26H32BBrNOP
(62.9)
62.0
(62.9)
(6.4)
6.1
(6.4)
(2.8)
2.5
(2.8)
4dB
Oil
5.9
(6.2)
(16.1)
4eA and 4eB
Oil
9-BBN for the hydroboration of 1a and 1c failed to give any of
the expected azaboretidinium salts and the starting materials
were recovered unchanged. It is known that monoisocampheyl-
borane (IpcBH2) is less sterically demanding than either 9-BBN
or (Ipc)2BH and it has been used with some success for the
hydroboration of hindered prochiral trans-alkenes.26 Con-
sequently, (1R)-(ϩ)-monoisopinocampheylborane, prepared in
situ by the slow addition of a cold, dilute solution of (1R)-(ϩ)-
α-pinene in THF to BH3ؒTHF in the same solvent at Ϫ5 ЊC,27
was caused to react with the compounds 1a–c in dichloro-
methane at room temperature and the reactions were moni-
tored by 31P NMR spectroscopy. In all successful reactions
a milky appearance was observed after complete addition of
the IpcBH2 and this is another useful way of monitoring the
J. Chem. Soc., Perkin Trans. 1, 1997
3511

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H
H
–
B
2
H
H
–
B
2
R1
R2
R1
R2
+
Ph2P
+
1N
+
Ph2P
+
1N
3
3
(i)
4
4
Br–
Br–
1a–e
i
i
5
5
o
o
CH3
CH3
p
p
m
m
4A
4B
4a R1 = R2 = –(CH2)4–
4b R1 = R2 = –(CH2)5–
4cA and 4c–B R1 = (S)–CHMePh, R2 = H
4dA and 4dB R1 = R2 = (S)–(CH2)3–CH(CH2OH)
4eA and 4eB R1 = R2 = (S)-CHMePh
Fig.
1
X-Ray crystal structure of rac-2-methoxy-1-(diphenyl-
phosphinoyl)propane 10. The asymmetric unit includes a second, iden-
tical molecule, whose numbering scheme has been incremented by 20
relative to the above molecule. Selected bond lengths (Å) and angles (Њ):
P(1)᎐O(1) 1.480(3)/1.477(3), P(1)᎐C(1) 1.807(4)/1.797(4), P(1)᎐C(5)
1.805(4)/1.810(5), P(1)᎐C(11) 1.798(4)/1.815(4); O(1)᎐P(1)᎐C(1)
114.4(2)/115.2(2), O(1)᎐P(1)᎐C(5) 112.1(2)/111.8(2), O(1)᎐P(1)᎐C(11)
111.2(2)/109.9(2), C(1)᎐P(1)᎐C(5) 105.2(2)/105.3(2), C(1)᎐P(1)᎐C(11)
106.9(2)/106.1(2), C(5)᎐P(1)᎐C(11) 106.6(2)/108.1(2).
CH3
(ii)
H
–
(iii)
B
1
Br–
R1
R2
+
Ph3P
+
N
2
3
4
CH3
H
+
N
5 CH3
Br–
–
B
1
R1
R2
+
Ph3P
8aA R1 = R2 = –(CH2)4–
8bA R1 = R2 = –(CH2)5–
8cA R1 = (S)–CHMePh, R2 = H
2
3
4
4a–c
5
CH3
(i) or (ii)
8cB R1 = (S)-CHMePh, R2 = H
m
m
p
o
i
p
o
R1
Ha
Ha
R1
2
Hb
2
Hb
2
1
i
CH3
Ph
N
N
2
1
3
P
1
R2
P
3
R2
and
1
3
H
CH3
i′
H2B
N
1
2
O
CH3
i′
o′
Hc
O
CH3
Hc
CH3
3
Br–
N
o′
4
H2B
p′
Ph3P
H
p′
m′
m′
5
Ph
OH
rac-9a R1 = R2 = –(CH2)4–
rac-9b R1 = R2 = –(CH2)5–
(+)-9cA R1 = (S)–CHMePh, R2 = H
(–)-9cB R1 = (S)-CHMePh, R2 = H
5
6
7
Scheme 2 Reagents and conditions: (i) BH3ؒTHF (1 ), dry CH2Cl2,
Ϫ1 ЊC for 1 h then room temp. for 20 h; (ii) (1R)-(ϩ)-α-pinene,
BH3ؒTHF (1 ), dry CH2Cl2, Ϫ1 ЊC for 1 h then room temp. for 20 h;
(iii) (1S)-(Ϫ)-α-pinene, BH3ؒTHF (1 ), dry CH2Cl2, Ϫ1 ЊC for 1 h then
room temp. for 20 h
+
m
o
i
p
Ha
Hb
1′
O
OCH3
2
1
P
+
PPh3
3
i′
success of the reaction. Addition proceeded cleanly to give the
expected azaboretidinium products, which are all insoluble in
diethyl ether and can be easily obtained in an analytically pure
state by a simple work-up procedure. The spectroscopic data
and specific rotation values indicate that the compounds 8aA,
8bA and 8cA are single diastereomers within the limits of the
experimental data (see Scheme 2 and Tables 4–6). The similar
reduction of 1d and 1e also gave single diastereomers although
yields were low (<10%) and the major product isolated was
the decomposition product 5 and the corresponding pinene–
boron–amine complexes. When the asymmetric hydroboration
of 1c was repeated using (1S)-(Ϫ)-IpcBH2 the other diastereo-
mer 8cB was obtained in high yield.
Conversion of the azaboretidinium salts rac-4a,b and 4cA to
the phosphine oxides rac-9a,b and cA was initially carried out
by heating the salts in a 30% w/w solution of sodium hydroxide
in aqueous methanol and gave the expected products, together
with rac-2-methoxy-1-(diphenylphosphinoyl)propane 10 and a
small amount of triphenylphosphine oxide (see Scheme 3).
Compound 10 has been fully characterised by spectroscopic
O
CH3
Hc
o′
10
p′
m′
Scheme 3 Reagents and conditions: (i) MeOH, NaOH aq. (30% w/w),
reflux, 3 h; (ii) NaOH aq. (30% w/w), reflux, 3 h
methods and by X-ray crystallography (see Fig. 1). In the unit
cell the molecules are orientated so that they form columns of
approximately parallel P᎐O groups, in which the oxygen of one
᎐
molecule is directed towards the phosphorus of its neighbour.
The two molecules, which comprise the asymmetric unit, alter-
nate within the column so that the alkyl substituent eclipses a
phenyl group of an adjacent molecule. A structural database
survey failed to identify any closely related molecules. This
compound probably arises as a by-product of formation of 9
according to the mechanism proposed in Scheme 4. Its form-
ation can be eliminated by carrying out the above reactions
in aqueous sodium hydroxide alone without addition of
methanol. The azaboretidinium salts are almost insoluble in
cold sodium hydroxide solution, but on heating reaction pro-
3512
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Table 5 1H, 31P and 11B NMR spectroscopic data for the compounds 4a–e, 8aA, 8bA and 8cAa
b
c
Comp.
δP
δB
δH(J/Hz)
3
4a
ϩ30.1
ϩ29.8
ϩ30.2
ϩ30.2
Ϫ7.5
Ϫ8.0
Ϫ7.5
Ϫ8.1
1.60 (d, 3H, JH᎐H 6.7, H5), 1.65–1.75 (m, 2H, H2Ј or H3Ј), 1.80–1.95 (m, 2H, H3Ј or H2Ј), 2.25–2.40 (m,
2H, H1Ј or H4Ј), 2.55–2.70 (overlapping dt, 1H, 2JHa᎐Hb 19.0, 3JHa Hb᎐H 9.1, H4Ј or H1Ј), 2.80–2.95 (over-
or
lapping dt, 1H, 2JHc᎐Hd 18.6, 3JHc Hd᎐H 9.3, H1Ј or H4Ј), 3.10–3.25 (m, 2H, H4 and H3) and 7.55–7.75 (m,
or
15H, Ph3P)
3
8aA
4b
0.65–1.20 [m, 10H, (α-pinene moiety)], 1.50–1.60 [m, 4H, (α-pinene moiety)], 1.65 (d, 3H, JH᎐H 6.7, H9),
1.70–1.80 (m, 2H, H7 or H6), 1.85–1.95 (m, 2H, H6 or H7), 2.20–2.35 (m, 2H, Ha or Hb and Hc or Hd), 2.50–
2.60 (overlapping dt, 1H, 2JHa᎐Hb 19.0, 3JHa or Hb᎐H 9.1, Ha or Hb), 2.80–2.95 (overlapping dt, 1H, 2JHc᎐Hd 18.6,
3JHc or Hd᎐H 9.3, Hc or Hd), 3.00–3.15 (m, 2H, H4 and H3) and 7.50–7.75 (m, 15H, Ph3P)
3
1.05–1.20 (m, 2H, H3Ј), 1.35–1.45 (m, 2H, H2Ј or H4Ј), 1.50 (d, 3H, JP᎐H 6.2, H5), 1.60–1.70 (m, 2H, H4Ј
2
or H2Ј), 1.80–1.95 (m, 1H, H1aЈ), 2.05–2.15 (m, 1H, H1bЈ), 2.45–2.55 (overlapping dt, 1H, JHa᎐Hb 16.4,
3JHa or Hb᎐H 5.3, H1Ј), 2.55–2.65 (overlapping dt, 1H, 2JHc᎐Hd 14.7, 3JHc or Hd᎐H 4.7, H1Ј), 3.00–3.10 (m, 2H, H3
and H4) and 7.55–7.75 (m, 15H, Ph3P)
8bA
0.70–1.20 [m, 10H, (α-pinene moiety)], 1.05–1.20 (m, 2H, H7), 1.35–1.45 (m, 2H, H6 or H8), 1.50 (d, 3H,
3JP᎐H 6.2, H10), 1.55–1.75 [m, 6H, (α-pinene moiety) and H8 or H6], 1.80–1.95 (m, 1H, Hb or Ha), 2.05–2.15
2
3
(m, 1H, Hc or Hd), 2.45–2.55 (overlapping dt, 1H, JHa᎐Hb 16.4, JHa
lapping dt, 1H, 2JHc᎐Hd 14.7, 3JHc or Hd᎐H 4.7, Hc or Hd), 3.05–3.15 (m, 2H,HHb᎐H3 and H4) and 7.50–7.80 (m, 15H,
5.2, Hc or Hd), 2.60–2.70 (over-
or
Ph3P)
4cA
ϩ29.1
Ϫ8.2
1.12 (d, 3H, 3JH᎐H 6.5, H2Ј), 1.40 (d, 3H, 3JH᎐H 6.8, H5), 2.95–3.05 [m (overlapping), 2H, H3 and H4], 3.30–
3.45 (dq, 1H, 3JNH᎐H 4.7, 3JH᎐H 6.5, H1Ј), 7.20–7.45 (m, 5H, Ph), 7.60–7.75 (m, 15H, Ph3P) and 7.90 (d, 1H,
3JNH᎐H 4.7, NH)
4cB
8cA
ϩ28.2
ϩ29.1
Ϫ8.0
Ϫ5.2
1.45 (d, 3H, 3JH᎐H 6.4, H2Ј), 1.80 (d, 3H, 3JH᎐H 6.8, H5), 2.85–3.00 (m, 2H, H3 and H4), 3.15–3.30 (dq, 1H,
3JH᎐H 6.4, 3JNH᎐H 3.1, H1Ј), 7.20–7.45 (m, 5H, Ph), 7.60–7.75 (m, 15H, Ph3P) and 8.65 (br s, 1H, NH)
0.60–1.14 [m, 10H, (α-pinene moiety)], 1.15 (d, 3H, 3JH᎐H 6.5, H11), 1.40 (d, 3H, 3JH᎐H 6.8, H10), 3.00–3.15 [m
(overlapping), 2H, H3 and H4], 3.30–3.45 (dq, 1H, 3JNH᎐H 4.7, 3JH᎐H 6.5, H5), 7.20–7.45 (m, 5H, Ph), 7.60–
7.75 (m, 15H, Ph3P) and 7.85 (d, 1H, 3JNH᎐H 4.7, NH)
4dA
4dB
ϩ29.5
ϩ29.8
Ϫ8.1
Ϫ8.0
Ϫ8.1
1.50 (d, 3H, 3JH᎐H 6.6, H5), 1.85 (m, 2H, H2Ј), 1.90 (m, 1H, H3Јa or b), 2.20 (m, 1H, H3Јb or a), 3.10–3.25 [m
(overlapping), 2H, H4 and H3], 3.50 (m, 1H, H1Јa or b), 3.55 (m, 1H, H1Јa or b), 3.85 (m, 1H, H5a), 4.20–4.35
(m, 2H, H5Јb and H4), 5.15 (t, 1H, 3JH᎐H 6.6, OH) and 7.50–7.80 (m, 15H, Ph3P)
1.10 (d, 3H, 3JH᎐H 6.6, H5), 1.75 (m, 2H, H2Ј), 1.85 (m, 1H, H3Јa or b), 2.10 (m, 1H, H3Јb or a), 3.00–3.15 [m
(overlapping), 2H, H3 and H4], 3.35 (m, 1H, H1Јa or b), 3.45 (m, 1H, H1Јa or b), 3.75 (m, 1H, H5a), 4.10–4.15
(m, 2H, H5b and H4), 5.15 (t, 1H, 3JH᎐H 6.6, OH) and 7.50–7.80 (m, 15H, Ph3P)
4e
(A ϩ B)
ϩ27.4
ϩ29.2
0.75 (d, 3H, 3JH᎐H 6.8, H5A), 1.10 (d, 3H, 3JH᎐H 6.8, H5B), 1.85 (d, 6H, 3JH᎐H 6.8, H2ЈA), 1.95 (d, 6H, 3JH᎐H
6.8, H2ЈB), 3.00–3.20 (m, 4H, H3 and H4), 3.45 (q, 1H, 3JH᎐H 6.8, H1ЈA), 3.70 (q, 1H, 3JH᎐H 6.8, H1ЈB) and
7.10–7.90 (m, 25H, Ph3P and Ph)
a All spectra were determined in CDCl3. b 85% H3PO4 as external reference. c BH3ؒEt2O as external reference.
Table 6 13C chemical shifts and 31P–13C coupling constants for the azaboretidinium bromide salts 4a–e and 8aA, 8bA and 8cA
δC(CDCl3) [J(31P–13C)/Hz]
Comp.
4a
3
4
5
i
o
m
p
Other bands
15.5
[53.2]
14.8
62.5
[1.2]
62.0
(1.2)
17.3
[0.0]
17.1
(0.0)
120.5
[86.9]
120.5
(86.9)
133.8
[9.6]
133.8
(9.6)
130.2
[12.3]
130.2
(12.3)
134.5
[1.5]
134.5
(1.5)
20.5, 59.6, 60.8
8aA
20.2, 20.4, 21.5, 23.5,
23.6, 27.4, 27.5, 29.5,
30.0, 37.4, 47.8, 59.6,
60.7
(54.2)
4b
14.5
[54.1]
14.8
66.4
[br.]
66.2
(br.)
15.9
[0.0]
15.9
(0.0)
121.0
[87.2]
120.5
(87.2)
134.0
[9.6]
133.7
(9.8)
130.4
[12.2]
130.0
(12.1)
134.4
[2.5]
134.4
(1.8)
20.7, 21.7, 22.6, 50.9,
60.0
20.5, 20.6, 21.5, 21.7,
22.5, 23.5, 23.7, 27.5,
27.6, 29.5, 30.0, 37.5,
47.7, 50.7, 59.8
8bA
(54.1)
4cA
4cB
8cA
15.5
[52.8]
26.1
[54.1]
15.1
58.5
[2.5]
47.5
[br.]
58.4
(2.4)
21.5
[1.9]
21.5
[br.]
21.5
(1.9)
121.0
[87.0]
117.1
[87.1]
121.0
(87.0)
133.7
[9.5]
134.0
[10.2]
133.7
(9.6)
130.0
[12.0]
130.8
[12.9]
130.0
(12.0)
134.5
[2.4]
135.8
[br.]
134.5
(1.9)
18.5, 65.7, 128.2, 128.5,
129.0, 139.0
15.5, 56.8, 128.0, 128.4,
129.5, 138.4
18.5, 20.3, 21.1, 23.4,
27.3, 27.4, 29.5, 30.1,
37.5, 47.8, 65.9, 128.1,
128.5, 129.0, 138.7
2.7, 27.6, 50.1, 57.3,
60.8, 61.9
(56.8)
4dA
4dB
17.5
[54.0]
25.5
57.6
[0.0]
57.2
[0.0]
18.5
[br.]
19.5
[0.0]
120.2
[87.3]
120.0
[87.3]
133.9
[9.4]
133.6
[9.4]
130.2
[12.2]
130.0
[12.2]
134.6
[2.4]
134.6
[2.4]
8.7, 23.5, 50.0, 60.0, 69.8
[54.2]
ceeds cleanly to give good yields of the phosphine oxides rac-
9a,b and cB, although some triphenylphosphine oxide is still
produced under these conditions. The physical and spectro-
scopic properties of the compounds rac-9a,b,cA and cB are
given in Tables 7–9. As expected, compound 9cB has similar
spectroscopic properties but the opposite specific rotation to
that of 9cA. Treatment of the pure diastereomers 8aA, 8bA and
8cA obtained by reduction using IpcBH2, with aqueous sodium
hydroxide gave almost quantitative yields of the correspond-
ing phosphine oxides (ϩ)-9aA, (ϩ)-9bA and (Ϫ)-9cA and no
triphenylphosphine oxide formation was observed in these
cases. The specific rotation of 9cA obtained from 8cA is almost
identical to that obtained from the oxidation of 4cA and this
establishes that the hydroboration using (R)-(ϩ)-monoiso-
pinocampheylborane occurs by attack on the si-face of 1c and,
conversely, (S)-(Ϫ)-monoisopinocampheylborane must react
J. Chem. Soc., Perkin Trans. 1, 1997
3513

View Article Online
(85%) as standards respectively. Optical rotations ([α]D) were
H
H
MeO
OMe
measured using an Optical Activity Ltd. AA-1000 polarimeter
and are given in units of 10Ϫ1 deg cm2 gϪ1. Chiral GC analysis
was carried out using a G-TA (trifluoroacetyl γ-cyclodextrin
30 m × 0.25 mm column). Low resolution mass spectra were
recorded on a Kratos MS 45 instrument and fast atom bom-
bardment (FAB) spectra were measured on a VG update AEI-
M5902 instrument using a matrix of p-nitrobenzyl alcohol.
Triphenyl(prop-2-ynyl)phosphonium bromide was prepared
by a previously described method.17,19 Pyrrolidine, piperidine,
(S)-(Ϫ)-1-phenylethylamine (ee 99%), and (S)-(ϩ)-pyrrolidine-
2-methanol (ee, 96%) were commercial samples used without
further purification. (S,SЈ)-N,N-bis(1-phenylethyl)amine was
prepared by the three step procedure reported by Hogeveen
et al.25 (1R)-(ϩ)-Monoisopinocampheylborane was prepared
by the addition of a solution of (1R)-(ϩ)-α-pinene in dry THF
to a cold solution of borane in the same solvent under an
atmosphere of argon followed by stirring at 0 ЊC for 2 h.27
B
B
Me
MeOH
Br–
Ph3P
NH
Ph
NH
Ph
Br–
Ph3P
Me
Me
H2
Me
4cA
Syn
H
MeO
OMe
Ph
E2
B
Me
Br–
Ph3P
NH
Br–
Ph3P
Ph
H
OMe
Me
Me
H
MeO
N
B
MeOH
MeO
Me
Me
Ph3P
Br–
MeO
OMe
Ph
General procedure for reactions of triphenyl(prop-2-ynyl)-
phosphonium bromide 2 with various amines
B
OMe
NH
Triphenyl(prop-2-ynyl)phosphonium bromide 2 (1 mol equiv.)
was dissolved in hot, dry acetonitrile (250 cm3). After cooling
the solution to room temperature, the amine (1 mol equiv.) was
added dropwise to the vigorously stirred solution over a period
of 10–15 min. The mixture was refluxed for 90 min and then
stirred over a period of 70–80 h at room temperature. The
reaction was monitored using 31P NMR spectroscopy and TLC
(hexane–Et2O, 1:3). When no starting material was present, the
white precipitate which had formed was filtered. The filtrate was
concentrated under reduced pressure to give more white pre-
cipitate. The concentrated filtrate, a yellow–brown oil, was then
dissolved in a small amount of hot dichloromethane, then ethyl
acetate was added slowly whilst the mixture was warmed in a
water bath until the solution became cloudy. The solution was
allowed to cool at room temperature, then left in the freezer for
48 h to give a further crop of the white precipitate. The solids
were combined and dried under vacuum to afford the desired
product.
(a) With pyrrolidine. Reaction between 2 (15.0 g, 39.4 mmol)
and pyrrolidine (2.80 g, 3.30 cm3, 39.4 mmol) in acetonitrile
(500 cm3) gave 2-methyl-2-pyrrolidinovinyl(triphenyl)phos-
phonium bromide 1a (16.0 g, 45.4 mmol, 90%); Rf 0.20 (hexane–
Et2O, 1:3).
(b) With piperidine. Compound 2 (7.62 g, 20.0 mmol) and
piperidine (1.70 g, 1.20 cm3, 20.0 mmol) in acetonitrile (250
cm3) afforded 2-methyl-2-piperidinovinyl(triphenyl)phosphon-
ium bromide 1b (6.97 g, 15.0 mmol, 75%); Rf 0.25 (hexane–Et2O,
1:3).
Ph3P
Br–
MeOH
Me
Me
Me
Ph3P
Br–
MeO– [– B(OMe)3]
OMe
H
N
NaOH
Ph
Br–
HO–
Ph3P
Me
OMe
Me
Me
Br–
Ph3P
HO–
H
H
O
H
O
N
Ph
Me
P
P
Ph2
Ph2
Me
Me
PhH
OMe
PhH
Me
H
N
O
Ph
O
P
P
Ph2
Ph2
Me
9cA
Me
OMe
10
Scheme 4 Proposed mechanism for the formation of 10 and 9cA from
4cA
(c) With (S)-(؊)-1-phenylethylamine. Reaction between (S)-
(Ϫ)-1-phenylethylamine (6.35 g, 4.16 cm3, 52.5 mmol) and 2
(20.0 g, 52.5 mmol) in acetonitrile (700 cm3) gave 2-methyl-2-
[N-(S)-(phenylethyl)amino]vinyl(triphenyl)phosphonium brom-
ide 1c (19.95 g, 39.74 mmol, 76%); Rf 0.27 (CHCl3–MeOH, 9:1)
[α]25389 Ϫ42.4 (c 0.5 g in 100 cm3 CH2Cl2).
(d) With (S)-(؉)-pyrrolidine-2-methanol. Reaction between 2
(7.62 g, 20.0 mmol) and (S)-(ϩ)-pyrrolidine-2-methanol (3.30 g,
20.0 mmol) in acetonitrile (250 cm3) with exclusion of light gave
a 1:2 mixture of rotamers of 2-methyl-2-[(S)-2-hydroxymethyl-
with the re-face to give 9cB. Chiral GC analysis of compound
(ϩ)-9bA shows an ee value of 75% and we assume that in this
case, and also the reaction of 1a with (R)-(ϩ)-IpcBH2 the
major product has the S-configuration, but we have been unable
to establish this unequivocally.
In summary, provided that the substituents on nitrogen are
non-bulky, the combination of reduction of an enamino-
(triphenyl)phosphonium salt with either of the antipodes of
IpcBH2, followed by treatment with 30% w/w aqueous sodium
hydroxide provides a rapid and quite versatile method for the
synthesis of optically pure β-aminophosphine oxides in three
steps from readily available triphenyl(prop-2-ynyl)phosphon-
ium bromide.
pyrrolidino]vinyl(triphenyl)phosphonium bromide 1d (7.52 g,
23
15.6 mmol, 78%); Rf 0.32 (CHCl3–MeOH, 9:1); [α] ϩ18.7
589
(c 0.80 g in 100 cm3 CH2Cl2).
(e) With (S,SЈ)-N,N-bis(1-phenylethyl)amine. Compound 2
(0.85 g, 2.23 mmol) and (S,SЈ)-N,N-bis(1-phenylethyl)amine
(0.50 g, 22.2 mmol) in acetonitrile (75 cm3) gave a red oil, which
was chromatographed (SiO2, CHCl3–MeOH, 9:1) to afford 2-
methyl-2-[(S,S)-N,N-bis(1-phenylethyl)amino]vinyl(triphenyl)-
phosphonium bromide 1e, as an off-white foam (1.19 g, 1.96
mmol, 88%); Rf 0.15 (CHCl3–MeOH, 9:1), [α]25389 Ϫ112.0 (c 0.50
g in 100 cm3 CH2Cl2).
Experimental
1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded on a Bruker AC300 spectrometer. J Values are given in
Hz. The 11B (64 MHz) and 31P (81 MHz) spectra were recorded
on a Bruker AC 200 instrument with H3BؒOEt2 and H3PO4
3514
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Table 7 Physical data for phosphine oxides 9a–c
Found (calc.) (%)
Comp.
rac-9a
rac-9b
rac-9cA
Yield (%)
Mp (ЊC)
70–71
Molecular formula
C19H24NPؒ0.5H2O
C20H26NP
C
H
N
P
m/z, [(M Ϫ H)ϩ]
54a
87b
48a
80b
55a
79b
71.1
(70.8)
73.1
(73.4)
75.7
(76.0)
7.7
(7.8)
7.9
(7.9)
7.0
(7.2)
4.4
(4.3)
4.2
(4.3)
3.8
(3.9)
9.5
(9.6)
9.4
(9.5)
8.2
(8.5)
314
328
364
125–126
109–110
C23H26NP
a Using aq. methanolic NaOH. b Using aqueous NaOH.
Table 8 1H and 31P NMR spectroscopic data for the phosphine oxides 9a–ca
b
Comp.
δP
δH(J/Hz)
rac-9a
ϩ30.3
1.14 (d, 3H, 3JH᎐Hc 6.9. H3), 1.55–1.70 (m, 4H, H2Ј and H3Ј), 2.15–2.30 (ddd, 1H, 2JHa᎐Hb 15.4, 3JHa᎐Hc 6.3, 2JP᎐Ha 14.5, H1a),
2.30–2.40 (m, 2H, H1Ј or H4Ј), 2.45–2.50 (m, 2H, H4Ј or H1Ј), 2.60–2.75 (ddd, 1H, 2JHb᎐Ha 15.4, 3JHb᎐Hc 12.5, 2JP᎐Hb 9.5,
H1b), 2.90–3.05 (ddq, 1H, 3JHc᎐H 6.9, 3JHc᎐Ha 6.3, 3JHc᎐Hb 12.5, H2), 7.30–7.45 (m, 6H, Ph) and 7.60–7.75 (m, 4H, Ph)
1.05 (d, 3H, 3JH᎐Hc 6.7, H3), 1.15–1.45 (m, 6H, H2Ј, H3Ј and H4Ј), 2.05–2.20 (ddd, 1H, 2JHa᎐Hb 15.5, 3JHa᎐Hc 6.3, 2JP᎐Ha 14.0,
H1a), 2.20–2.40 (m, 4H, H1Ј and H5Ј), 2.50–2.65 (ddd, 1H, 2JHb᎐Ha 15.5, 3JHb᎐Hc 12.5, 2JP᎐Ha 9.9, H1b), 3.00–3.20 (ddq, 1H,
3JHc᎐H 6.7, 3JHc᎐Ha 6.5, 3JHc᎐Hb 12.5, H2), 7.30–7.50 (m, 6H, Ph) and 7.65–7.80 (m, 4H, Ph)
rac-9b
ϩ30.9
ϩ30.6
rac-9cA
1.10 (d, 3H, 3JH᎐Hc 6.0, H3), 1.22 (d, 3H, 3JH᎐H 6.6, H2Ј), 1.80 (br, s, 1H, NH), 2.30–2.35 (ddd, 1H, 2JHa᎐Hb 15.3, 3JHa᎐Hc 5.8,
2
3
2
3
3
2JP᎐Ha 14.8, H1a), 2.35–2.55 (ddd, 1H, JHb᎐Ha 15.3, JHb᎐Hc 12.1, JP᎐Hb 10.0, H1b), 2.90–3.05 (ddq, 1H, JHc᎐H 6.0, JHc᎐Ha
5.8, 3JHc᎐Hb 12.1, H2), 3.80 (q, 1H, 3JH᎐H 6.6, H4), 7.15–7.25 (m, 5H, Ph), 7.30–7.50 (m, 6H, Ph2P) and 7.55–7.70 (m, 4H,
Ph2P)
3
3
2
3
2
rac-9cB
ϩ31.9
1.12 (d, 3H, JH᎐Hc 6.0, H3), 1.35 (d, 3H, JH᎐H 6.6, H2Ј), 2.35–2.45 (ddd, 1H, JHa᎐Hb 15.3, JHa᎐Hc 5.8, JP᎐Ha 14.8, H1a),
2 3 2 3
2.35–2.55 (ddd, 1H, JHb᎐Ha 15.3, JHb᎐Hc 12.1, JP᎐Hb 10.0, H1b), 2.75 (br, s, 1H, NH), 3.00᎐3.10 (ddq, 1H, JHc᎐H 6.0,
3JHC᎐Ha 5.8, JHc᎐Hb 12.1, H2), 3.85 (q, 1H, JH᎐H 6.6, H4), 7.15–7.25 (m, 5H, H1Ј), 7.30᎐7.50 (m, 6H, Ph) and 7.55–7.70
3
3
(m, 4H, Ph)
a All spectra were determined in CDCl3. b 85% H3PO4 as external reference.
Table 9 13C chemical shifts and 31P–13C coupling constants for phosphine oxides 9a᎐c
δC(CDCl3) [J(31P–13C)/Hz]a
Comp.
1
2
3
i (iЈ)
o (oЈ)
m (mЈ)
p (pЈ)
Other bands
rac-9a
34.3
[70.5]
52.2
[1.9]
19.2
[3.0]
133.2
[98.9]
134.0
[98.9]
133.2
[99.3]
134.5
[98.7]
132.8
[98.7]
134.2
[97.9]
130.3
[9.2]
130.5
[9.3]
130.4
[9.1]
130.7
[8.9]
130.4
[10.2]
130.5
[10.3]
128.3
[11.9]
128.4
[11.6]
128.3
[11.7]
128.4
[11.5]
128.3
[11.5]
128.5
[11.6]
131.3
[2.9]
131.4
[2.9]
131.1
[3.1]
131.2
[2.7]
131.4
[3.2]
131.5
[3.2]
23.1, 23.4, 49.1, 49.4
rac-9b
33.1
[70.5]
54.7
[br.]
16.3
[4.9]
24.7, 25.9 (br), 49.1 (br)
rac-9cA
36.6
[69.5]
46.5
[2.3]
23.3
[7.2]
24.1, 55.4, 126.4, 126.7,
128.0, 146.0
a Shifts for iЈ, oЈ, mЈ and pЈ are given in italics.
Hydroboration of enamino(triphenyl)phosphonium salts with
borane
wise until all the white precipitate had dissolved. The acidic
solution was then neutralised using saturated aqueous sodium
carbonate, and the product was then extracted with chloroform
(3 × 40.0 cm3). The combined extracts were dried over
anhydrous MgSO4, filtered, then concentrated under reduced
pressure to afford an oil. Slow addition of ethyl acetate to the
oil gave the product as a white precipitate, which was filtered.
Synthesis of 4a. Compound 1a (5.0 g, 11.06 mmol) in
dichloromethane (20 cm3) and a 1  solution of borane in
tetrahydrofuran (50.0 cm3, 50.0 mmol) gave [(2R,3S)- and
(2R,3R)-3-methyl-4-azonia-1-boranuidaspiro[3.4]octan-2-yl]-
triphenylphosphonium bromide 4a (4.60 g, 9.87 mmol, 89%) as a
white solid.
Synthesis of 4b. Reaction between 1b (5.0 g, 10.73 mmol) in
dichloromethane (20.0 cm3) and 1  solution of borane in
tetrahydrofuran (50.0 cm3, 50.0 mmol) gave {(2R,3S)- and
(2R,3R)-(3-methyl-4-azonia-1-boranuidaspiro[3.5]nonan-2-yl}-
triphenylphosphonium bromide 4b (4.00 g, 8.33 mmol, 78%).
Synthesis of 4c. Compound 1c (5.0 g, 9.96 mmol) dissolved
in the minimum amount of dichloromethane (20.0 cm3) was
General procedure. A solution of the phosphonium salt in the
minimum amount of anhydrous dichloromethane was cooled in
an ice–salt bath and stirred continuously under an atmosphere
of argon. When the temperature of the solution had reached
Ϫ1 to Ϫ2 ЊC, a cold solution of borane in tetrahydrofuran (1 )
was added dropwise to the vigorously stirred solution over a
period of 25 min. The mixture was stirred at approximately
Ϫ1 ЊC for 1 h, after which, the ice–salt bath was removed and
the mixture was then stirred for a further 2 h at room temper-
ature. The reaction was monitored using 31P NMR spec-
troscopy. When the 31P NMR spectrum showed that the
reaction was complete, the flask was placed in an ice–salt bath,
a condenser was fitted and anhydrous methanol (0.5 cm3) was
added dropwise until vigorous effervescence had stopped.
Deionised water (5.0 cm3) was added, again dropwise, until
no more effervescence was observed. The ice–salt bath was
removed, the mixture was allowed to warm to room temper-
ature and aqueous hydrogen bromide (10%) was added drop-
J. Chem. Soc., Perkin Trans. 1, 1997
3515

View Article Online
caused to react with a 1  solution of borane in tetrahydrofuran
(50.0 cm3, 50.0) to afford, after work-up, a viscous pale yellow
oil which contained a 1:1 mixture of two diastereomers (4cA
and B) (4.32 g, 8.39 mmol, 84%).
133.4 (d, Co, 2JP᎐Co 10.6) and 135.0 (d, Cp, 4JP᎐Cp 3.1); δP(CDCl3,
81 MHz, 85% H3PO4 ref.) ϩ19.2.
The third set of fractions contained a single diastereomer of
{(2R,3S,4S)-5-[(S)-hydroxymethyl]-3-methyl-4-azonia-1-boran-
uidaspiro[3.4]octan-2-yl}triphenylphosphonium bromide 4dA
obtained as a white foam (1.85 g, 3.73 mmol, 28%); Rf 0.45
(CHCl3–MeOH, 8:2 ); [α]25389 Ϫ44.0 (c 0.91 g in 100 cm3 CH2Cl2).
The final set of fractions contained the other diastereoisomer
{(2S,3R,4S)-5-[(S)-hydroxymethyl]-3-methyl-4-azonia-1-boran-
uidaspiro[3.4]octan-2-yl}triphenylphosphonium bromide 4dB
as a pale yellow oil (1.46 g, 2.94 mmol, 22%); Rf 0.30
(CHCl3–MeOH, 8:2); [α]25389 ϩ21.0 (c 0.62 g in 100 cm3 CH2Cl2).
Synthesis of 4e. Reaction between 1e (0.72 g, 1.19 mmol) in
dichloromethane (12 cm3) and 1  borane in tetrahydrofuran
(6.0 cm3, 6.0 mmol) gave a pale yellow oil, which contained a
1:1 mixture of two diastereomers (4eA and B), and two other
products 5 and 7 (0.69 g, 1.11 mmol, 92%).
The oil was first dissolved in the minimum amount of
dichloromethane, then ethyl acetate was added slowly until a
fine white precipitate was formed. The solution was then left in
the freezer for 24 h. The precipitate was filtered under reduced
pressure, and then dried under vacuum. The concentrated fil-
trate was then dissolved in the minimum amount of dichloro-
methane, and ethyl acetate was added slowly until more white
precipitate appeared. The solution was then left in the freezer
for 48 h. The precipitate was filtered under reduced pressure,
then dried under vacuum. This procedure was repeated until no
further precipitate was obtained after leaving the flask in the
1
freezer for six weeks. A H NMR spectrum of the combined
precipitates indicated a 7:3 mixture of diastereomers, about
85% pure. The precipitate was then recrystallised from propan-
2-ol, by carefully dissolving it in the minimum amount of
warm propan-2-ol, keeping the temperature of the propan-2-ol
below 50 ЊC. The flask was left at room temperature for 2 days
during which time small, needle-shaped, white crystals began
to crystallise. The flask was then placed in the freezer and left
undisturbed for another 7 days. The solid was filtered under
reduced pressure to afford crystals suitable for X-ray determin-
ation and finally dried under vacuum to afford a pure
single diastereomer, [(1S,3R,4S,1ЈS)-4-methyl-1-(1-phenylethyl)-
1,2-azaboretidin-1-ium-2-uid-3-yl]triphenylphosphonium brom-
ide 4cA (1.53 g, 2.96 mmol, 30%); [α]25389 Ϫ180.5 (c 0.29 g in 100
cm3 CH2Cl2).
The mixture was impossible to separate by fractional crystal-
lisation using a variety of solvent systems, but separation was
achieved by column chromatography (SiO2, CHCl3–MeOH,
8:2) using an extremely slow rate of solvent flow and collecting
small fractions.
The first compound collected was (S,SЈ)-N,N-bis(1-phenyl-
ethyl)aminoborane 7 (0.192 g, 0.81 mmol, 68%) as an oil; Rf
23
0.82 (CHCl3–MeOH, 8:2); [α] Ϫ29.5 (c 0.15 g in 100 cm3
589
CH2Cl2); νmax(neat)/cmϪ1 2422m (B᎐H, st. vib.), 2346m (B᎐H,
st. vib.) and 1438s (B᎐N, st. vib.); δH(CDCl3, 300 MHz) 1.25 (d,
6H, 3JH᎐H 6.7, H2), 3.50 (q, 2H, 3JH᎐H 6.7, H1) and 7.20–7.80 (m,
10H, Ph); δC(CDCl3, 75 MHz) 25.0 (C2), 55.5 (C1), 126.5 (C4),
126.5 (C3), 128.5 (C5) and 145.9 (C3); δB(CDCl3, 64 MHz,
BH3ؒEt2O ref.) Ϫ7.1; m/z (FAB) 237 [(Mϩ), 50%].
The remaining pale yellow oil was washed several times with
chloroform, then dried under vacuum to afford a 9:1 mixture
of diastereomers as a pale yellow viscous oil containing
predominantly [(1S,3R,4R,1ЈS)-4-methyl-1-(1-phenylethyl)-1,2-
The second set of fractions contained (E)-prop-1-enyl-
(triphenyl)phosphonium bromide 5 (0.42 g, 1.10 mmol, 92%)
and the final set of fractions were a 1:1 mixture of the dia-
azaboretidin-1-ium-2-uid-3-yl]triphenylphosphonium
bromide
stereomers,
{(3R,4S)-4-methyl-1,1-bis[(S)-1-phenylethyl]-1,2-
bromide
4cB (1.95 g, 3.78 mmol, 38%); [α]25389 ϩ100.5 (c 0.31 g in 100 cm3
CH2Cl2).
azaboretidin-1-ium-2-uid-3-yl}triphenylphosphonium
4eA and {(3S,4R)-4-methyl-1,1-bis[(S)-1-phenylethyl]-1,2-aza-
boretidin-1-ium-2-uid-3-yl}triphenylphosphonium bromide 4eB
as a clear viscous oil (0.019 g, 0.030 mmol, 2.5%); Rf 0.24
(CHCl3–MeOH, 8:2).
Synthesis of 4d. A solution of 1d (5.0 g, 13.1 mmol) in the
minimum amount of anhydrous dichloromethane (25.0 cm3),
on reaction with 1  borane in tetrahydrofuran (65.0 cm3, 65.0
mmol) gave, after work-up, a pale yellow oil (5.56 g, 11.2 mmol,
86%), which contained a 1:1 mixture of diastereomers 4dA,
4dB and two other minor products 5 and 6.
Hydroboration of enamino(triphenyl)phosphonium salts with
(1R)-(؉)-monoisopinocampheylborane
It proved impossible to separate the mixture by fractional
crystallisation using a variety of solvent systems, but the use of
column chromatography (SiO2, CHCl3–MeOH, 8:2) and
an extremely slow rate of solvent flow led to the successful
separation of the diastereomers 4dA and 4dB, and 5 and 6.
The first compound collected was (R)-(ϩ)-1-borylpyrrol-
General procedure. A solution of the phosphonium salt in
anhydrous dichloromethane (20.0 cm3) was stirred continuously
in an ice–salt bath under an atmosphere of dry argon. When the
temperature of the solution had reached Ϫ7 to Ϫ5 ЊC, a cold
solution of freshly prepared (1R)-(ϩ)-monoisopinocampheyl-
borane (10.0 mmol) in tetrahydrofuran was added via a narrow
bore steel cannula to the vigorously stirred solution over 15
min. A milky white solution formed and the mixture was ini-
tially stirred at approximately Ϫ1 ЊC for 3 h, and then overnight
at room temperature. The reaction was monitored using 31P
NMR spectroscopy. When the 31P NMR spectrum showed that
the reaction was complete the flask was placed in an ice–salt
bath and bench chloroform (20.0 cm3) was added dropwise
until no effervescence was observed. Diethyl ether (30.0 cm3)
was added slowly to give the product as a white precipitate. The
solvent layer was carefully removed via a narrow bore steel
cannula and the precipitate was washed several times with
diethyl ether (30.0 cm3), then finally dried under vacuum to
afford the product.
Synthesis of 8aA. Reaction between 1a (1.0 g, 2.21 mmol)
in dichloromethane (20 cm3) and (1R)-(ϩ)-monoisopino-
campheylborane (10.0 mmol) in tetrahydrofuran gave, after
work-up, {(2R,3S)-1-[(R)-isopinocampheyl]-3-methyl-4-azonia-
1-boranuidaspiro[3.4]octan-2-yl}triphenylphosphonium bromide
8aA (1.21 g, 2.01 mmol, 91%) as a fine, white solid; [α]25689 Ϫ8.4 (c
0.86 g in 100 cm3 CH2Cl2); νmax(CHBr3 mull)/cmϪ1 2432s (B᎐H,
st. vib.), 2342m (B᎐H, st. vib.) and 1438s (B᎐N, st. vib.).
idine-2-methanol 6 (0.220 g, 1.95 mmol, 15%) as a colourless
23
589
oil; Rf 0.80 (CHCl3–MeOH, 8:2); [α] ϩ10.5 (c 0.84 g in 100
cm3 CH2Cl2); νmax(CHBr3 mull)/cmϪ1 3300m (br sharp, O᎐H,
st. vib.), 2422m (B᎐H, st. vib.), 2346m (B᎐H, st. vib.), 1438s
(B᎐N, st. vib.); δH(CDCl3, 300 MHz) 1.85 (m, 2H, H2), 1.90 (m,
1H, H3a), 2.20 (m, 1H, H3b), 3.50 (m, 1H, H1a), 3.55 (m, 1H,
H1b), 3.85 (m, 1H, H5a), 4.15–4.30 (m, 2H, H5b and H4) and
3
5.00 (t, 1H, JH᎐H 6.6, OH); δC(CDCl3, 75 MHz) 22.5 (C3),
27.6 (C2), 49.5 (C1), 61.5 (C4) and 62.6 (C5); δB(CDCl3, 64
MHz, BH3ؒEt2O ref.) Ϫ7.0; m/z (EI/CI) 130 [(Mϩ ϩ NH3),
100%].
The second set of fractions gave (E)-prop-1-enyl(triphenyl)-
phosphonium bromide 5 (0.85 g, 2.22 mmol, 17%) as a white
solid; Rf 0.70 (CHCl3–MeOH, 8:2); mp 210–211 ЊC [Found: C,
65.5; H, 5.5; Br, 20.9; P, 8.0. m/z (FAB) 303 [(Mϩ Ϫ BrϪ), 100%.
Calc. for C21H20BrP: C, 65.8; H, 5.2; Br, 20.9; P, 8.1%, M, 383];
δH(CDCl3, 300 MHz) 2.25 (dt, 3H, 3JH᎐Hb 6.5, 4JCH ᎐Ha 1.9, H3),
6.50–6.80 [ddq, 2H, 3JH᎐H 16.5 (trans), 3JH᎐H 6.5, 2JP3 ᎐Ha 22.1, H1
and H2] and 7.65–7.90 (m, 15H, Ph3P); δC(CDCl3, 75 MHz)
3
21.5 (d, C3, JP᎐C 20.1), 110.0 (d, C1, JP᎐C 86.4), 159.4 (d, C2,
3
2JP᎐C 2.9), 118.0 (d, Ci, JP᎐Ci 90.7), 130.2 (d, Cm, JP᎐Cm 12.7),
3516
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Synthesis of 8bA. A mixture of compound 1b (1.0 g, 2.16
mmol) in dichloromethane (20.0 cm3) and (1R)-(ϩ)-mono-
isopinocampheylborane (10.0 mmol) in tetrahydrofuran
reacted to afford {(2R,3S)-1-[(R)-isopinocampheyl]-3-methyl-
4-azonia-1-boranuidaspiro[3.5]nonan-2-yl}triphenylphosphon-
ium bromide 8bA (1.26 g, 2.04 mmol, 95%) as a fine white solid;
[α]25489 Ϫ2.1 (c 2.13 g in 100 cm3 CH2Cl2); νmax(CHBr3 mull)/cmϪ1
2432s (B᎐H, st. vib.), 2342m (B᎐H, st. vib.) and 1438s (B᎐N, st.
vib.).
Synthesis of 8cA. Compound 1c (1.0 g, 1.99 mmol) in
dichloromethane (20.0 cm3) was caused to react with (1R)-(ϩ)-
monoisopinocampheylborane (10.0 mmol) in tetrahydrofuran
to give {(3R,4S,1ЈS)-2-[(R)-(ϩ)-isopinocampheyl]-4-methyl-1-
(1-phenylethyl)-1,2-azaboretidin-1-ium-2-uid-3-yl}triphenylphos-
selected for X-ray measurements. Unit cell dimensions were
determined from the setting angle of 25 accurately centred
reflections (6.0 < θ < 11.5Њ). 4583 Independent reflections were
measured on a Siemens R3m/v diffractometer using graphite
monochromated Mo-Kα radiation (λ = 0.710 73 Å, 2θ < 50Њ)
with ω/2θ scans. Data were collected at 233(2) K and the
structure was solved by direct methods using SHELXS-8628
and DIRDIF.29 Refinement was by full-matrix least-squares
methods on F2 for all independent reflections. wR2 =
2
2
2
2
2
¹
²
{[Σw(Fo Ϫ Fc ) /Σw(Fo ) ]} = 0.2997 for all data, where w =
2
1/[σ2(Fo ) ϩ (0.0979p)2 ϩ 0.8577p], where p = (Fo2 ϩ 2Fc2)/3.
Conventional R [on F values for 3016 reflections with
F2 > 2σ(F2)] = 0.067 goodness of fit = 1.082 on F2 for 343
refined parameters. All atoms were refined anisotropically.
Hydrogen atoms were constrained to chemically reasonable
positions.
Atomic coordinates, bond lengths and angles, and thermal
parameters have been deposited at the Cambridge Crystallo-
graphic Data Centre (CCDC). For details of the deposition
scheme, see ‘Instructions for Authors’, J. Chem. Soc., Perkin
Trans. 1, 1997, Issue 1. Any request to the CCDC for this
material should quote the full literature citation and the
reference number 207/155.
(b) Using aqueous sodium hydroxide. A mixture of 4a (1.0 g,
2.15 mmol) and aqueous sodium hydroxide (30%, w/w, 10.0
cm3) was refluxed for 3 h. The mixture was then extracted with
chloroform (3 × 30 cm3) and the combined extracts were dried
under vacuum to afford a white solid, which by 31P NMR
spectroscopy was a mixture of two phosphorus compounds
(δ ϩ30.3 and ϩ29.8). This mixture was successfully separated
by column chromatography (SiO2, CHCl3–MeOH, 9:1) to give
triphenylphosphine oxide (0.07 g, 0.26 mmol, 12%) and 9a
(0.59 g, 1.88 mmol, 87%).
phonium bromide 8cA (1.12 g, 1.72 mmol, 86%) as a white solid;
23
[α] Ϫ100.5 (c 0.39 g in 100 cm3 CH2Cl2); νmax(CHBr3 mull)/
589
cmϪ1 2432s (B᎐H, st. vib.), 2342m (B᎐H, st. vib.) and 1435s
(B᎐N, st. vib.).
Hydrolysis of [(2R,3S)- and (2R,3R)-3-methyl-4-azonia-1-
boranuidaspiro[3.4]octan-2-yl]triphenylphosphonium bromide
4a
(a) Using sodium hydroxide in methanol. A solution of 4a (2.0
g, 4.29 mmol) in methanol (40.0 cm3) was stirred vigorously and
aqueous sodium hydroxide (30%, w/w, 10.0 cm3) was added
slowly. The mixture was stirred at room temperature for 3 h,
then refluxed for 3 h. The reaction was monitored using 31P
NMR spectroscopy. When the 31P NMR spectrum showed that
the reaction was complete, the mixture was cooled to room
temperature before extraction with chloroform (3 × 30 cm3).
The combined extracts were dried over anhydrous MgSO4, then
concentrated under reduced pressure and finally dried under
vacuum to afford a white solid shown by 31P NMR spec-
troscopy to contain three different phosphorus compounds
(δ ϩ30.3, ϩ29.5 and ϩ29.8 ppm). The mixture was successfully
separated by column chromatography (SiO2, EtOAc–CH2Cl2,
4:1).
Hydrolysis of {(2R,3S)-1-[(R)-isopinocampheyl]-3-methyl-4-
azonia-1-boranuidaspiro[3.4]octan-2-yl}triphenylphosphonium
bromide 8aA
The first compound separated was triphenylphosphine oxide
(0.14 g, 0.50 mmol, 12%); Rf 0.40 (EtOAc–CH2Cl2, 4:1); mp
151–152 ЊC followed by rac-2-methoxy-1-(diphenylphosphin-
oyl )propane 10, as a colourless oil (0.38 g, 1.39 mmol, 32%);
Rf 0.20 (EtOAc–CH2Cl2, 4:1). On leaving the colourless oil dis-
solved in small amount of chloroform at room temperature
over several months fine, needle-shaped crystals suitable for
X-ray determination were obtained, mp 65–66 ЊC; [α]25389 ϩ0.4 [c
0.19 g in 100 cm3 CH2Cl2 (AR)] (Found: C, 70.2; H, 6.7; P, 11.2.
C16H19O2P requires C, 70.1; H, 6.9; P, 11.3%); νmax(CHBr3 mull)/
Compound 8aA (0.50 g, 0.830 mmol) in chloroform (1.0 cm3)
and aqueous sodium hydroxide (30%, w/w, 5.0 cm3) were
refluxed for 3 h whilst stirring. The mixture was extracted with
chloroform (3 × 30 cm3) and the combined extracts were dried
over anhydrous MgSO4, filtered, then concentrated under
reduced pressure and finally dried under vacuum to afford a
pale yellow oil, which on treatment with diethyl ether (15.0 cm3)
gave a white precipitate. The precipitate was washed several
times with diethyl ether (10.0 cm3), dried under vacuum to
finally afford (S)-(ϩ)-2-pyrrolidino-1-(diphenylphosphinoyl)-
propane-(ϩ)-9a (0.252 g, 0.805 mmol, 97%) as a white solid; mp
70–71 ЊC; [α]25689 ϩ11.9 (c 2.64 g in 100 cm3 CH2Cl2). The spectro-
scopic data were identical to those of the racemate reported
previously.
cmϪ1 2356w (P᎐H, st. vib.), 2257w (P᎐H, st. vib.), 1181s (P᎐O,
᎐
st. vib.) and 1088s (P᎐O, st. vib.); δ (CDCl , 300 MHz) 1.25 (d,
᎐
H
3
3H, 3JH᎐Hc 6.1, H3), 2.25–2.40 (ddd, 1H, 2JHa᎐Hb 15.3, 3JHa᎐Hc 6.3,
2JP᎐Ha 14.4, H1a), 2.60–2.75 (ddd, 1H, 2JHb᎐Ha 15.3, 3JHb᎐Hc 12.3,
2JP᎐Hb 9.4, H1b), 3.10 (s, 3H, H3), 3.65–3.80 (ddq, 1H, 3JHc᎐H 6.1,
3
3JHc᎐Ha 6.3, JHc᎐Hb 12.3, H2), 7.35–7.50 (m, 6H, Ph) and 7.65–
Hydrolysis of {(2R,3S)- and (2R,3R)-(3-methyl-4-azonia-1-
boranuidaspiro[3.5]nonan-2-yl}triphenylphosphonium bromide
4b
3
7.80 (m, 4H, Ph); δC(CDCl3, 75 MHz) 21.0 (d, C3, JP᎐C 7.2),
37.5 (d, C1, JP᎐C 70.6), 56.0 (C1Ј), 72.0 (br s, C2), 128.2 (d, Cm,
3JP᎐Cm 12.3), 128.9 (d, CmЈ, 3JP᎐CmЈ 12.3), 130.5 (d, Co, 2JP᎐Co 9.4),
131.0 (d, CoЈ, 2JP᎐CoЈ 9.4), 131.5 (d, Cp, 4JP᎐Cp 2.0), 131.7 (d, CpЈ,
4JP᎐CpЈ 2.1), 133.1 (d, Ci, JP᎐Ci 99.8) and 134.3 (d, CiЈ, JP᎐CiЈ 99.3);
δP(CDCl3, 81 MHz, 85% H3PO4 ref.) ϩ29.6; m/z (FAB) 275
[(M ϩ H)ϩ, 100%].
The final compound collected after eluting the column with
a more polar solvent (MeOH–CH2Cl2, 8:2) was rac-2-
pyrrolidino-1-(diphenylphosphinoyl)propane 9a (0.72 g, 2.30
mmol, 54%) as an off-white solid; Rf 0.02 (EtOAc–CH2Cl2,
4:1); [α]25389 ϩ0.2 (c 0.21 g in 100 cm3 CH2Cl2).
(a) With sodium hydroxide in methanol. Following the pro-
cedure described above a solution of 4b (2.0 g, 4.17 mmol)
in methanol (40.0 cm3) was stirred vigorously with aqueous
sodium hydroxide (30%, w/w, 10.0 cm3) and the mixture was
stirred at room temperature for 3 h, then refluxed for 3 h to
afford a white solid after work-up. A 31P NMR spectrum
showed that the white solid contained three different phos-
phorus compounds (δ ϩ30.9, ϩ29.5 and ϩ29.8). This mixture
was successfully separated by column chromatography (SiO2,
EtOAc–CH2Cl2, 4:1) to give triphenylphosphine oxide (0.16 g,
0.575 mmol, 14%) followed by rac-2-methoxy-1-(diphenyl-
phosphinoyl)propane 10 (0.42 g, 1.53 mmol, 37%). The final
compound collected after eluting the column with a more polar
solvent (MeOH–CH2Cl2, 8:2) was rac-2-piperidino-1-(diphenyl-
phosphinoyl)propane 9b (0.66 g, 2.02 mmol, 48%); Rf 0.02
Crystal data for 10. C16H19O2P, M = 274.28, triclinic, space
¯
group P1, a = 8.608(3), b = 11.736(4), c = 15.925(5) Å, α =
76.71(3), β = 85.58(3), γ = 71.34(2)Њ, U = 1483.4(9) Å3, Z = 4,
Dc = 1.228 g cmϪ3, F(000) = 584, µ(Mo-Kα) = 0.181 mmϪ1. A
colourless needle shaped crystal (0.40 × 0.20 × 0.10 mm) was
J. Chem. Soc., Perkin Trans. 1, 1997
3517

View Article Online
(EtOAc–CH2Cl2, 4:1); [α]25389 ϩ0.1 (c 0.20 g in 100 cm3 CH2Cl2)
as an off-white solid.
pounds (δ ϩ30.6 and ϩ29.8). This mixture was successfully
separated by column chromatography (SiO2, CHCl3–MeOH,
9:1) to give triphenylphosphine oxide (0.04 g, 0.14 mmol, 15%)
and [(2R,4S)-(ϩ)-2-methyl-4-phenyl-3-azapentyl]-diphenylphos-
phine oxide (ϩ)-9cB (0.26 g, 0.72 mmol, 74%); Rf 0.35 (CHCl3–
MeOH, 9:1); [α]25689 ϩ98.3 (c 0.15 g in 100 cm3 CH2Cl2).
(b) With aqueous sodium hydroxide. A mixture of 4b (1.0 g,
2.08 mmol) and aqueous sodium hydroxide (30%, w/w, 10.0
cm3) was refluxed for 3 h and then extracted with chloroform
(3 × 30 cm3). The combined extracts were dried over anhydrous
MgSO4, filtered, then concentrated under reduced pressure and
finally dried under vacuum to afford a white solid containing
two phosphorus compounds (δ ϩ30.9 and ϩ29.8). This mixture
was successfully separated by column chromatography (SiO2,
CHCl3–MeOH, 9:1) to give triphenylphosphine oxide (0.07 g,
0.25 mmol, 12%) and rac-2-piperidino-1-(diphenylphosphinoyl)-
propane 9b (0.56 g, 1.71 mmol, 80%).
Acknowledgements
Thanks are due to Dr R. G. Pritchard for the X-ray crystal
structure determinations on compounds 4cA and 10.
References
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Hydrolysis of {(2R,3S)-1-[(R)-isopinocampheyl]-3-methyl-4-
azonia-1-boranuidaspiro[3.5]nonan-2-yl}triphenylphosphonium
bromide 8bA
Reaction between 8bA (0.50 g, 0.812 mmol) in chloroform (1.0
cm3) and aqueous sodium hydroxide (30%, w/w, 5.0 cm3) gave a
pale yellow oil, which on treatment with diethyl ether (15.0 cm3)
gave (R)-(ϩ)-2-piperidino-1-(diphenylphosphinoyl)propane (ϩ)-
9bA (0.260 g, 0.79 mmol, 98%) as a white solid; mp 125–126 ЊC;
[α]25689 ϩ8.6 [c 0.33 g in 100 cm3 CH2Cl2 (AR)]. The spectroscopic
data were identical to those of the racemate 9b reported previ-
ously. Chiral GC analysis of a solution of this compound in
chloroform showed it to be a mixture of enantiomers with an ee
value of 75%.
Hydrolysis of (1S,3R)-4-methyl-1-[(S)-phenylethyl]-1,2-aza-
boretidin-1-ium-2-uid-3-yl]triphenylphosphonium bromide 4cA
(a) With sodium hydroxide in methanol. Under the general
conditions described a solution of 4cA (1.0 g, 1.94 mmol) in
methanol (20.0 cm3) was heated with aqueous sodium hydrox-
ide (30%, w/w, 10.0 cm3) to afford a white solid after work-up.
A
31P NMR spectrum showed that the white solid contained
a mixture of three different phosphorus compounds, having
the following chemical shifts δ ϩ30.6, ϩ29.5 and ϩ29.8. The
mixture was successfully separated by column chromatography
(SiO2, EtOAc–CH2Cl2, 4:1) to give triphenylphosphine oxide
(0.8 g, 0.278 mmol, 14%) followed by rac-2-methoxy-1-
(diphenylphosphinoyl)propane 10 (0.42 g, 1.53 mmol, 37%).
The final compound collected as a colourless oil after eluting
the column with a more polar solvent (MeOH–CH2Cl2, 8:2)
was [(2S,4S)-2-methyl-4-phenyl-3-azapentyl]diphenylphosphine
oxide 9cA (0.39 g, 1.07 mmol, 55%); Rf 0.02 [EtOAc–CH2Cl2,
4:1); [α]25389 Ϫ150.2 (c 0.20 g in 100 cm3 CH2Cl2).
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Hydrolysis of {(3R,4S,1ЈS)-2-[(R)-(؉)-isopinocampheyl]-4-
methyl-1-(1-phenylethyl)-1,2-azaboretidin-1-ium-2-uid-3-yl}-
triphenylphosphonium bromide 8cA
To 8cA (0.50 g, 0.767 mmol) in chloroform (1.0 cm3) was added
aqueous sodium hydroxide (30%, w/w, 5.0 cm3). The mixture
was refluxed for 3 h whilst stirring to give, after work-up,
[(2S,4S)-(Ϫ)-2-methyl-4-phenyl-3-azapentyl]diphenylphosphine
oxide (Ϫ)-9cA (0.27 g, 0.74 mmol, 97%); [α]25689 Ϫ162.3 (c 1.61 g
in 100 cm3 CH2Cl2). The melting point and spectroscopic data
were identical to those of 9cA reported previously.
27 H. C. Brown, N. Inoue, M. W. Rathke and K. R. Varma, J. Am.
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Oxidation of [(1S,3S,4R,1ЈS)-4-methyl-1-(1-phenylethyl)-1,2-
azaboretidin-1-ium-2-uid-3-yl]triphenylphosphonium bromide
4cB
Under similar conditions 4cB (0.50 g, 0.971 mmol) on heating
with aqueous sodium hydroxide (30%, w/w, 10.0 cm3) gave a
white solid, which contained two different phosphorus com-
Paper 7/03936K
Received 5th June 1997
Accepted 4th August 1997
3518
J. Chem. Soc., Perkin Trans. 1, 1997