Synthesis, structure and comparative stability of β-hydrazono, oximino methyl ether and imino boronates

Article abstract of DOI:10.1039/b004573j

β-Hydrazono and oximino ether boronates have been prepared by the sequential lithiation of the corresponding methyl hydrazone or oxirhe methyl ether, followed by reaction with an iodomethylboronate ester, typically in the form of the pinacol ester. The resulting products have contrasting hydrolytic stabilities. β-Hydrazono boronates are highly sensitive to intramolecularly catalysed hydrolysis, providing the corresponding β-keto boronates in generally high yields; β-oximino ether boronates are stable to silica gel chromatography and show evidence of E-Z-isomerisation. Stable homochiral boronate ester derivatives of β-oximino ethers can be readily prepared by a double transesterification process, via a diethanolamine-mediated pinacol ester exchange, followed by diethanolamine ester hydrolysis-reesterification process with a homochiral diol. β-Imino boronates can be generated in situ by condensation of the corresponding β-keto boronate with a primary amine, however the resulting imine function is highly hydrolytically unstable and cannot be isolated in a pure form. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b004573j

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Synthesis, structure and comparative stability of ꢀ-hydrazono,
oximino methyl ether and imino boronates
Richard J. Mears,a Helen E. Sailes,a John P. Wattsb and Andrew Whiting*a
1
a Department of Chemistry, Faraday Building, U.M.I.S.T., P.O. Box 88, Manchester,
UK M60 1QD
b Knoll Pharmaceuticals, Pennyfoot Street, Nottingham, UK NG1 1GF
Received (in Cambridge, UK) 7th June 2000, Accepted 4th August 2000
First published as an Advance Article on the web 18th September 2000
β-Hydrazono and oximino ether boronates have been prepared by the sequential lithiation of the corresponding
methyl hydrazone or oxime methyl ether, followed by reaction with an iodomethylboronate ester, typically in the form
of the pinacol ester. The resulting products have contrasting hydrolytic stabilities. β-Hydrazono boronates are highly
sensitive to intramolecularly catalysed hydrolysis, providing the corresponding β-keto boronates in generally high
yields; β-oximino ether boronates are stable to silica gel chromatography and show evidence of E–Z-isomerisation.
Stable homochiral boronate ester derivatives of β-oximino ethers can be readily prepared by a double transesterifi-
cation process, via a diethanolamine-mediated pinacol ester exchange, followed by diethanolamine ester hydrolysis–
reesterification process with a homochiral diol. β-Imino boronates can be generated in situ by condensation of the
corresponding β-keto boronate with a primary amine, however the resulting imine function is highly hydrolytically
unstable and cannot be isolated in a pure form.
Introduction
Chiral boronate esters have been demonstrated to be useful for
controlling the remote asymmetric reduction of carbonyl func-
tions in γ-keto boronate substrates 11 and β-keto boronate sys-
tems 2,2 to provide the corresponding chiral secondary alcohols
with high asymmetric induction. In both cases, intramolecular
boronate–ketone complexes are implicated in controlling the
asymmetric reduction process.3 By direct analogy with this
method, we proposed that the 1,6-diastereoselective reduction
of imine derivatives 3 (Scheme 1), could have potential appli-
cation in the enantioselective synthesis of β-amino acids 4.4
Fig. 1
due to enhanced boron–nitrogen chelation (Fig. 1), resulting
from the increased lone pair basicity of nitrogen versus oxygen.
We therefore examined the suitability of different C᎐N
equivalents for directed asymmetric reduction by means of a
remote chiral boronate ester group and recently reported our
preliminary results in this area.5 In this paper, we report the full
details about the synthesis and structure of different β-boronate
᎐
C᎐N derivatives.
᎐
Results and discussion
ꢀ-Hydrazono boronates
In earlier work, we had prepared various β-boronate carbonyl
systems via the alkylation of an enolate with an α-haloboronate
ester6 for application in stereocontrolled aldol reactions.7 Dur-
ing this work, the application of hydrazone-stabilised anions
was also developed in order to improve certain β-keto boronate
syntheses.6 However, such substrates are also potentially suit-
able for the reduction process proposed in Scheme 1, if the
hydrazones were sufficiently stable. Thus we prepared a series of
hydrazones 7 according to Scheme 2 and Table 1.
In all cases, the hydrazones 7 could not be isolated in a pure
form direct from Scheme 2; complete or partial hydrolysis
always occurred during the aqueous work-up of the reaction
mixture, with further hydrolysis occurring upon silica gel
chromatography. Presumably the hydrolysis is catalysed by the
presence of the intramolecular boronate function assisting with
the hydrolysis process, as shown in Fig. 2, involving chelation
Scheme 1
Thus, an enantiomerically pure boronate system such as 3,
would be expected to react with hydride equivalents via an
activated intramolecular B–N complex as shown in Fig. 1. Sub-
sequent oxidative cleavage of the boronate directly to the carb-
oxylic acid and removal of the nitrogen substituent (if not
removed under the C᎐N reduction conditions) would provide
᎐
an asymmetric route to β-amino acids 4. Indeed, β-imino bor-
onate ester compounds of general type 3 could reasonably be
expected to be equal to, or more efficient than, their ketone
counterparts 1 and 2 in directing remote asymmetric reduction
of the dimethylamino function (binding to the C᎐N function
᎐
cannot be ruled out as an alternative mode of hydrazone
3250
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
DOI: 10.1039/b004573j
This journal is © The Royal Society of Chemistry 2000

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Table 1
Table 2
Yield
Cu(OAc)2
required
E:Z ratio Yield of E:Z ratio Yield of
Entry
R
of 8 (%)a
Entry
R
of 10a
10 (%)b
of 11a
11 (%)b
1
2
3
4
5
Me
Et
59
66
75
51
35
No
No
Yes
No
Yes
1
2
3
4
5
6
7
Ph
Me
Et
1:0
—
3:1
3:1
7.8:1
1:0
96
29
79
62
44
67
56
1:0
1:3
0:1
1:0
1:0
1:0
1:0
82
80
79
64
48
79
61
Ph
iPr
nPr
iPr
tBu
C8H17
a Isolated yield after silica gel chromatography.
CH3(CH2)3- 6:1
CHCH3
8
nC8H17
2.7:1
54
1:0
48
a Determined by 1H NMR. b Isolated yield after silica gel chromato-
graphy.
Table 3 Selected analytical data for oxime ethers 10a–h
Oxime
ether
Entry 10
δH (ppm)a
δC
(ppm)b
C᎐N
᎐
c
R
Isomer CH3C᎐Nc OCH3
᎐
1
2
a
b
Ph
Me
E
—
2.2
3.9
149.7
154.6
1.84 (syn) 3.82
1.87 (anti)
3
4
5
6
7
8
9
10
c
d
e
Et
Pr
iPr
E
Z
E
Z
E
Z
E
E
1.82
1.85
1.81
1.84
1.76
1.77
1.79
1.73
3.83
3.81
3.83
3.80
3.82
3.80
3.82
3.82
158.6
159.3
157.6
158.0
161.5
162.4
163.2
161.2
f
g
tBu
CH3(CH2)3-
CHCH3
11
12
13
Z
E
Z
1.75
1.81
1.84
3.79
3.84
3.80
162.0
157.8
158.4
h
C8H17
a 300 MHz, CDCl3. b 75.5 MHz, CDCl3. c Singlet.
Scheme 2
activation). The intramolecular intervention of the boronate
moiety is reinforced by the 11B NMR studies on crude system
7a (after a non-aqueous work-up), which exhibited a resonance
at δ 5; clearly indicative of a boronate “ate”-complex of the
type suggested in Fig. 2.
Fig. 2
was determined by 1H NMR and the assignment of C᎐N bond
᎐
geometry was consistent with extensive structural studies
reported by Karabatsos.9 The α-methyl group chemical shifts
for the Z-isomers were found to be consistently downfield com-
pared to those for the corresponding E-oxime ether isomers
(Table 3, entries 3–8 and 10–13). The thermodynamically
favoured E-oxime isomer, in which the small α-methyl and
oxime methoxy functions are cis, was observed predominantly
in all cases (Table 3).
Regioselective alkylation of the lithiated anions derived from
oxime ethers 10c–h with iodomethylboronate ester 6, yielded
β-boronate oximes 11c–h as single stereoisomers in modest to
good yields after a swift acidic work-up (Scheme 2) (Table 2).
Similar chemical shifts were observed for the oxime methoxy
The hydrolytic sensitivity of the hydrazone systems 7 meant
that it was necessary to examine the preparation of alternative
C᎐N derivatives, in which the C᎐N bond was stable in the pres-
᎐
᎐
ence of the boronate function. Such stability was essential, if we
were to access chiral boronate analogues of type 3. The use of
oxime methyl ethers was therefore examined.
ꢀ-Oximino methyl ether boronates
The synthesis of various β-boronate oxime methyl ethers 11
was undertaken via alkylation of the corresponding methyl
O-methyloximes8 10, as shown in Scheme 3 and Table 2.
1
Comparison of the H NMR spectrum of the oxime ether
product 10a with that reported,8 confirmed the presence of
a single stereoisomer, the thermodynamically favoured anti-
oxime (E) (Table 2, entry 1). Subsequent deprotonation of
oxime ether 10a with LDA at Ϫ78 ЊC and subsequent treatment
with iodomethylboronate 6, successfully provided oxime ether
11a as a single E-stereoisomer. The synthesis of a series of
aliphatic β-boronate oxime ethers 11 was similarly achieved
(Table 2). In the aliphatic cases, mixtures of E- and Z-
stereoisomers were obtained for products 10, except for oxime
ethers 10b and f. The ratio of cis- and trans-isomers (Z to E)
groups in the H NMR of the boronates 11 compared to sys-
1
tems 10. In addition, the 11B NMR spectra of systems 11 in
CDCl3 at room temperature did not show any evidence for
boron chelation, showing the presence of an uncoordinated
boron atom in each of the cases 11a–h.
Attempts to elucidate the geometry of the oxime ether C᎐N
᎐
bonds in compounds 11 by NOE experiments were universally
unsuccessful. Therefore, the oxime ether stereochemistry was
initially assigned by assuming kinetic deprotonation of the
parent oxime ether 10 α-methyl group, followed by alkylation
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
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Scheme 3
Scheme 4
of the preferred syn-oxime ether anion with iodide 6. Retention
bond, even at low temperatures, ensuring conversion to the syn-
of C᎐N geometry was presumed providing the corresponding
monoanion11 12 (Scheme 4), which is more stabilised than
the corresponding anion 14. Extensive theoretical studies on the
structure of metalated oximes and oxime ethers, have confirmed
the stability of the syn-anion isomer 12.12 Therefore, alkylation
of 12 with iodomethylboronate ester 6 (Scheme 4), via complex
13, would provide boronate 11 with the methoxy and R groups
in the trans-configuration, as shown in Scheme 4. Lithiated
acetone O-methyloxime anion 12 (R = Me) has been reported13
to form a Z-bromomethyl-oxime ether, which readily isomerises
to the thermodynamically favoured E-form in the presence
of HBr. Thus, it is expected that O-methyloxime 11b (where
R = Me), will isomerise readily upon aqueous acidic work-up.
The remaining β-boronate oxime ethers prepared, i.e. 11a and
c–h, are all conformationally stable under the reaction and
work-up conditions described (Scheme 4).
᎐
β-boronate ester product 11, in which the oxime methoxy and
boron-containing substituent possess a cis-relationship. How-
ever, later studies revealed that treatment of acetone O-methyl-
oxime 10b with LDA and quenching with iodide 6, yielded a
3:1 mixture of Z- to E-stereoisomers (Table 2). However,
standing in CDCl3 overnight caused a reversal in the Z:E ratio,
to give a 1:3 mixture. Isomerisation of the substrate 11b is
presumably catalysed by the residual acid in the solvent. Such
an effect was not observed for β-oxime boronate esters 11a and
c–h. This suggests that, under the reaction conditions described
for the alkylation of 10 to give 11, R groups larger than methyl
produce a syn-relationship between the oxime methoxy func-
tion and boronate unit. It was also found that isomerisation of
substrates 11b–d could also occur on silica gel during chrom-
atography. Attempted purification by flash column chromato-
graphy of α-ethyl- and α-propyl-substituted oxime ethers, 11c
and 11d, furnished mixtures of stereoisomers, i.e. 1:1 and 2:1
respectively.
Having successfully prepared a range of stable, achiral
pinacol-based β-boronate O-methyloximes 11, routes for the
preparation of the required chiral β-boronate oxime ether sub-
strates 16 were investigated, as summarised in Scheme 5. Thus,
using the deprotonation–alkylation sequence used for the prep-
aration of boronates 11, using iodide 15 in place of achiral
iodide 6, would furnish chiral ester 16. Whereas transesterifi-
cation of the pinacol ester of 11 with chiral diol 17 would also
provide boronate 16.
It has been reported10 that acyclic ketone N,N-dimethyl-
hydrazones show little preference for syn- or anti-deprotonation
of otherwise equivalent methylene groups, however syn-anions
are more thermodynamically stable and equilibration does
occur.10 In comparison, it has been reported that oxime ethers
favour formation of a syn-oxime anion 12 upon deprotonation
of E–Z-isomers 10, with rapid isomerisation about the C–N
The C2-symmetric chiral auxiliary (S,S)-17 was achieved
using
a simple four-step procedure developed in our
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J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263

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Scheme 5
laboratories3a starting from (Ϫ)-dimethyl -tartrate. However,
(1)
high-pressure (1000 psi) catalytic hydrogenation at room tem-
perature using an autoclave was found to be more reliable for
the deprotection of benzylidene derivative 18. Similarly, the
could be isolated in excellent yields (90%) by transesterification
of the corresponding diethanolamine derivative 24 with the
appropriate diols 17 or 19 (Scheme 7), i.e. using a method which
antipode of 17, i.e. (R,R)-19 was prepared from (ϩ)-dimethyl
-tartrate.3a The preparation of iodomethylboronate 15 was
subsequently investigated, as outlined in Scheme 6.
Scheme 7
Scheme 6
is directly analogous to the chiral β-ketoboronate system 2 pre-
viously reported.3a It is again noteworthy that esters 23 and 25
showed no evidence of boron chelation (either by nitrogen or
oxygen) by 11B NMR in CDCl3 at room temperature.
The enantiomerically pure chloromethylboronate ester 20
was synthesised using an analogous method to that developed
for the synthesis of chloromethylboronate pinacol ester6
(Scheme 6). The corresponding iodomethylboronate 15 was
subsequently accessed in quantitative yield by treatment of
chloride 20 with sodium iodide in acetone. An identical strategy
was used to prepare the corresponding enantiomers 21 and 22.
ꢀ-Imino boronates
Having discovered that β-hydrazone boronates 7 were hydro-
lytically unstable, efforts were directed towards the preparation
of the β-imino boronate esters of type 3, where R2 = alkyl or
aryl. It was envisaged that such species may be prepared via
the condensation of the corresponding β-keto boronate ester,
such as 2, by condensation with a primary amine (eqn. (2)). The
(2)
Deprotonation of acetophenone O-methyloxime 10a with
LDA at Ϫ78 ЊC, followed by alkylation with iodomethylbor-
onate 15, afforded chiral β-boronate O-methyloxime (S,S)-23
as a single diastereoisomer, albeit in low yield (eqn. (1)).
In contrast, using a transesterification route (see Scheme 5) to
the chiral boronate oxime systems proved much more efficient.
Thus, both antipodes of the β-oxime boronate ester 23 and 25
required β-keto boronates 8 were prepared either via the
hydrazone route (Scheme 2) or by hydrolysis of the oxime ether
derivatives 11, as shown in Scheme 8.14 Subsequent transesteri-
fication to provide the chiral boronates 26 was carried out by
reaction with diethanolamine followed by diethanolamine ester
displacement with the chiral diol 19.
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
3253

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Scheme 8
Having accessed chiral ketones 26, conversion to the corre-
presence of a 3:5 mixture of diastereoisomers in CDCl3
solution at room temperature.
sponding imine derivatives 3 (R2 = alkyl or aryl) was examined.
Ketimines are frequently prepared by azeotropic distillation of
a mixture of ketone and amine with benzene or toluene to
remove the water formed in the reaction, or by directly distilling
water as it is produced. The condensation reaction is acid
catalysed, and catalysts such as TiCl4,15 ZnCl2,16 and toluene-
p-sulfonic acid,17 have been successfully used. Reaction of a
ketone with an amine in the presence of a drying agent such as
magnesium sulfate18 or molecular sieves,19 is also a convenient
method for imine preparation. Indeed, Westheimer reported
that molecular sieves serve as both a catalyst and a dehydrating
agent in the preparation of imines.20 It was therefore necessary
to determine whether such methods could be used to derive
β-imino boronates 3.
Presumably, the major diastereoisomer present in solution
is the thermodynamically favoured E-isomer, in which the
phenyl substituent and the N-benzyl substituent are anti, thus
minimising unfavourable steric interactions. Accordingly, it was
observed that chemical shift values for protons corresponding
to the CH B and CH C᎐N methylene groups, as well as the
᎐
2
2
boronate ester methoxy and CHO methine units, were consist-
ently upfield in the major diastereomer E-isomer, in which the
N-benzyl and boron-containing substituents are syn, compared
to those values for the minor Z-isomer.
It was also found that direct reaction of homochiral ketone
26g with excess benzylamine, with removal of water by distil-
lation of the excess benzylamine under reduced pressure, gave
the desired β-imino boronate ester 27a (Conditions c, Scheme
9), unfortunately however, this material was contaminated by
the presence of traces of various contaminants, including start-
ing materials and ketone 26g, amongst others. It was not pos-
sible to obtain an analytically pure sample of imine 27a by any
of these methods.
As a preliminary study, imine derivatives of β-keto boronate
ester (R,R)-26g were prepared from the corresponding pinacol-
derived ketone 8c by transesterification with diol (R,R)-19 via
the diethanolamine derivative (Scheme 9). Initial attempts to
Conclusions
Having accessed various C᎐N boronate systems 3, it is possible
᎐
clearly to compare the relative stability of each of the three
systems derived. β-Hydrazono boronate systems 7 are not suf-
ficiently stable to allow isolation, due to the internal activation
of the boronate function. In contrast, β-oximino ether boron-
ates 11 behave quite differently. In parallel with their carbonyl
counterparts, there is no evidence of internal boronate–
nitrogen or oxygen chelation as shown by 11B NMR. In
addition, these systems are readily manipulated to access the
desired chiral boronate esters, typified by structures 23 and 25.
The β-imino boronates, such as 27, appear to have similar
instability to the hydrazone systems and these findings strongly
suggested that any attempts to derive β-amino acids 4 via imine
derivatives 3 (R = alkyl) would require in situ generation of the
imine, such as 27, due to their high sensitivity to hydrolysis,
which can largely be attributed to presence of the boronate
function.
Scheme 9 Conditions: a, BnNH2, ∆ or PhH, or PhMe, ∆; b, BnNH2,
4 Å molecular sieves, CDCl3; c, neat BnNH2, ∆.
Experimental
isolate enantiomerically pure β-imino boronate ester 27a either
by treatment of chiral β-boronate ketone 26g by azeotropic
distillation with benzene or toluene (Conditions a, Scheme 9)
gave no evidence for imine formation (1H NMR, IR, or MS),
due to the extreme sensitivity towards hydrolysis of the imine
product 27a formed. However, when the condensation reaction
of β-keto boronate ester 26g with benzylamine, was directly
Hydroxyacetone was purchased from Fluka. All other reagents
were obtained from Acros, Aldrich or Lancaster. Dimethyl
sulfoxide and ethanolamine were stored under argon, over
activated 3 Å molecular sieves. Dry tetrahydrofuran was freshly
distilled from sodium and benzophenone immediately prior to
use. Dry dichloromethane was distilled from calcium hydride.
Bromochloromethane and diisopropylamine were distilled
from calcium hydride before use under an argon atmosphere.
Flash column chromatography was achieved using Acros silica
gel, pore size 60 Å, or Lancaster silica gel 60, 0.060–0.2 mm
(70–230 mesh). Thin layer chromatography was performed on
1
monitored by H NMR under strictly anhydrous conditions
(Conditions b, Scheme 9), the formation of imine 27a could
1
be observed directly to be occuring. Examination of the H
NMR spectrum of the β-imino boronate ester 27a revealed the
3254
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263

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Merck plastic or aluminium sheets coated with silica gel 60 F254
(Art. 5735). Chromatograms were initially examined under UV
light and then developed by spraying with either phospho-
molybdic acid (6 g in 125 ml of ethanol) or aqueous potassium
permanganate, followed by heating. All anhydrous reactions
were carried out in oven-dried (120 ЊC) glassware which was
cooled under a stream of argon. Organic extracts were dried
over MgSO4 before evaporation. Evaporations were achieved
using a Büchi rotary evaporator followed by drying at ca. 5
mmHg using a vacuum pump. Bulb-to-bulb distillations were
carried out using a Büchi GKR-51 Kugelrohr apparatus. Melt-
ing points were determined using an Electrothermal melting
point apparatus and are uncorrected. NMR spectra were
dropwise to neat butan-2-one (10 ml, 0.112 mol) at room tem-
perature and the solution stirred for 12 hours. After refluxing
for an hour, the resulting water layer was removed and refluxing
continued for a further hour. The reaction mixture was dried
with calcium hydride after removal of any residual water by
pipette. Fractional distillation from calcium hydride through
a Vigreux column, furnished the hydrazone 5b (12.07 g,
0.106 mol, 95%) as a colourless liquid; νmax (film) inter alia
1635 (C᎐N) cmϪ1; δC (CDCl3) (E)-isomer, 11.2 (CH3CH2), 15.7
᎐
(CH C᎐N), 31.9 (CH C᎐N), 46.7 ((CH ) N), 168.3 (C᎐N);
᎐
᎐
᎐
3
2
3 2
(Z)-isomer, 10.8 (CH CH ), 21.8 (CH C᎐N), 24.2 (CH C᎐N),
᎐
᎐
2
3
2
3
47.3 ((CH ) N), 170.0 (C᎐N). Anal. Calculated for C H N : C,
᎐
3
2
6
14
2
63.1; H, 12.4; N, 24.5. Found: C, 62.8; H, 12.7; N, 24.8%.
1
recorded using Bruker NMR spectrometers. H NMR and 13C
NMR spectra were recorded using CHCl3 and CDCl3 respect-
ively, as internal standards. Resonances for 11B NMR spectra
are quoted relative to BF3ؒEt2O (δ 11B = 0.00 ppm) as external
standard. Chemical shift values (δ) are given in ppm, coupling
constants (J) are given in Hz, and NMR peaks are described as
singlet (s), doublet (d), triplet (t), quartet (q) and multiplet (m).
Infrared (IR) spectra were recorded on a Perkin-Elmer 298
spectrophotometer or a Matson Unicam FTIR spectrometer.
Electron impact (EI) (70 eV) and chemical ionisation (CI) were
recorded with a Kratos MS50 or a Finnigan MAT 95S
spectrometer. Fast atom bombardment (FAB) spectra were
recorded on a Kratos MS50 using a m-nitrobenzyl alcohol
matrix. Accurate mass determinations were carried out on a
Kratos Concept IS spectrometer. Microanalyses were per-
formed using a Carlo-Erba 1106 elemental analyser. Optical
rotations were determined using a Perkin-Elmer Model 241 or
an Optical Activity AA-1000 polarimeter and are given in units
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pentan-3-one 8b
To a vigorously stirred solution of diisopropylamine (1.43 ml,
10.2 mmol) in THF (30 ml) at 0 ЊC was added butyllithium (4.1
ml, 2.5 M in hexanes, 10.2 mmol) under argon. After 20 min-
utes butanone N,N-dimethylhydrazone 5b (1.07 g, 9.3 mmol)
was introduced and the temperature maintained at 0 ЊC for a
further 30 minutes, resulting in a white suspended precipitate.
Cooling the solution to Ϫ78 ЊC, followed by addition of iodo-
methylboronate ester 6 (2.50 g, 9.3 mmol) and warming to
room temperature after 10 minutes gave a clear, pale yellow
solution which was quenched with saturated ammonium
chloride after 12 hours. Partitioning between ethyl acetate and
saturated ammonium chloride (two extractions), and an addi-
tional extraction of the combined aqueous phase with ethyl
acetate, was followed by drying of the combined organic
phase (MgSO4). Removal of the solvent by rotary evaporation
and high vacuum, and subsequent Kugelrohr distillation (90–
100 ЊC, 0.1 mmHg), furnished the boronate ester 8b (1.28 g,
6.1 mmol, 66%) as a pale yellow oil; νmax (film) inter alia 1718
of 10Ϫ1 deg cm2 gϪ1
.
Acetone N,N-dimethylhydrazone 5a
(C᎐O) cmϪ1; δB (CDCl3) ϩ33.1; δH (CDCl3) 0.90 (2 H, t, J = 7.2
᎐
This compound was prepared according to the procedure of
Eliel21 on a 0.395 mol scale, and furnished hydrazone 5a (21.40
g, 0.214 mol, 54%) as a colourless liquid after distillation.
IR and NMR spectra were as reported. Additional data:
δ (13C, CDCl ) 17.39 and 24.5 [E- and Z-((CH ) C᎐N)], 46.4
Hz, CH2B), 1.04 (3 H, t, J = 7.4 Hz, CH3CH2), 1.22 (12 H,
s, 2 × (CH3)2CO), 2.40 (2 H, q, J = 7.2 Hz, CH3CH2), 2.55
(2 H, t, J = 7.1 Hz, C᎐OCH CH ); δ (CDCl3) ~5 (br, CH2B),
᎐
2
2
C
8.1 (CH CH ), 24.7 ((CH ) CO), 35.2 (C᎐OCH CH B), 36.7
᎐
3
2
3
2
2
2
᎐
3
3
2
(CH CH ), 83.0 ((CH ) CO), 212.6 (C᎐O); m/z (FAB) 213
᎐
3 2 3 2
3
2
5
12
2
(M ϩ H)ϩ, 154 (M Ϫ C3H6O)ϩ; high resolution mass spectrum,
calculated for C11H22BO3 (M ϩ H)ϩ 213.1662, found 213.1662.
((CH ) N), 163.9 (C᎐N). Anal. Calculated for C H N : C, 60.0;
᎐
H, 12.0; N, 28.0. Found: C, 59.7; H, 12.3; N, 28.3%.
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-one 8a
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)propiophenone
8c
To a vigorously stirred solution of diisopropylamine (0.30 ml,
4.1 mmol) in tetrahydrofuran (10 ml) at 0 ЊC was added butyl-
lithium (1.65 ml, 2.5 M in hexanes, 4.1 mmol). After 20 minutes,
hydrazone 5a (0.37 g, 3.7 mmol) was added dropwise and the
temperature maintained at 0 ЊC for a further 20 minutes, the
formation of a fine, cloudy precipitate occurring after 5–10
minutes. Cooling the solution to Ϫ78 ЊC, followed by addition
of iodomethylboronate ester 6 (1.00 g, 3.7 mmol) resulted in a
homogeneous solution which was allowed to warm to room
temperature after 10 minutes. The reaction was quenched
after 4 hours at room temperature with saturated ammonium
chloride. Partitioning between ethyl acetate and saturated
ammonium chloride was followed by drying of the organic phase
(MgSO4). Removing the solvent by rotary evaporation and high
vacuum furnished a pale yellow oil, which after Kugelrohr dis-
tillation (75 ЊC, 0.5 mmHg) yielded the boronate ester 8a (0.44
To a vigorously stirred solution of diisopropylamine (4.76 ml,
40.0 mmol) in tetrahydrofuran (160 ml) at 0 ЊC under argon was
added butyllithium (16.56 ml, 2.5 M in hexanes, 41.4 mmol).
After 20 minutes hydrazone 5c22 (5.00 g, 30.9 mmol) was intro-
duced and the temperature maintained at 0 ЊC for a further 2
hours, resulting in a thick yellow suspension. Cooling the solu-
tion to Ϫ78 ЊC, followed by addition of iodomethylboronate
ester 6 (8.26 g, 30.7 mmol) and warming to room temperature
after 5 minutes, gave a clear pale orange solution which was
stirred for a further 12 hours. The reaction was quenched
with saturated ammonium chloride followed by partitioning
between ethyl acetate (400 ml) and saturated ammonium chlor-
ide (2 × 100 ml). Drying the combined organic phases (MgSO4)
and removal of solvent by rotary evaporation and high vacuum
gave a viscous, pale yellow oil, of which the hydrazone 7c was
found to be the major component by 1H NMR. Dissolving the
oil in tetrahydrofuran (300 ml) at room temperature was fol-
lowed by addition of aqueous copper() acetate (300 ml of a
0.2 M solution, 62 mmol) and the solution stirred for 12 hours.
The tetrahydrofuran was removed by rotary evaporation and
saturated ammonium chloride added to the aqueous solution.
Partitioning the solution between ethyl acetate and saturated
ammonium chloride, and washing the organic phase with a sat-
urated sodium bicarbonate solution, gave a dark brown oil after
drying the organic phase (MgSO4) and rotary evaporation.
g, 2.2 mmol, 59%) as a pale yellow oil; νmax inter alia 1716 (C᎐O)
᎐
cmϪ1; δ (11B, CDCl3) ϩ33.8; δH (CDCl3) 0.90 (2 H, t,
J = 7.4 Hz, CH2B), 1.23 (12 H, s, 2 × (CH3)2CO), 2.13 (3 H, s,
CH C᎐O), 2.59 (2 H, t, J = 7.1 Hz, CH C᎐O); δ (CDCl3) ~5
᎐
᎐
3
2
C
(br, CH B), 24.8 ((CH ) CO), 28.9 (CH C᎐O), 38.4 (CH C᎐O),
᎐
᎐
2
2
3
2
3
83.0 ((CH ) CO), 209.2 (C᎐O); m/z (FAB), CsI additive,
᎐
3
2
(M ϩ Cs)ϩ.
Butan-2-one N,N-dimethylhydrazone 5b
N,N-Dimethylhydrazine (10 ml, 0.132 mol) was introduced
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
3255

View Article Online
Kugelrohr distillation (120 ЊC, 0.5 mmHg) of this residue fur-
nished the boronate ester 8c (6.05 g, 23.2 mmol, 75%) as a pale
yellow oil, which was identical to that previously reported.6
m, (CH ) ), 1.45 (2 H, m, CH ), 1.92 (3 H, s, CH C᎐N), 2.17 (2
᎐
2 5 2 3
H, t, J = 7.6 Hz, CH C᎐N), 2.41 (6 H, s, (CH ) N); (Z)-isomer,
᎐
2
3 2
all signals coincident with (E)-isomer except 1.89 (3 H, s,
CH C᎐N), 2.38 (6 H, s, (CH ) N); δ (CDCl3) (E)-isomer,
᎐
3
3
2
C
14.1 and 16.4 (CH C᎐N and CH CH ), 22.7, 27.1, 29.1, 29.2,
᎐
3-Methylbutan-2-one N,N-dimethylhydrazone 5d
3
3
2
29.3, 31.9 and 39.1 ((CH ) ), 47.0 ((CH ) N), 168.1 (C᎐N); (Z)-
᎐
2
7
3 2
N,N-Dimethylhydrazine (39 ml, 0.513 mol) was slowly intro-
duced to neat 3-methylbutan-2-one (50 ml, 0.467 mol), and the
stirred solution refluxed for 6 hours. After cooling, the reaction
mixture was partitioned between diethyl ether and water,
and the organic phase dried (MgSO4). Rotary evaporation and
fractional distillation at water aspirator vacuum (74 ЊC)
through a Vigreux column, furnished the hydrazone 5d (43.71 g,
0.341 mol, 73%) as a colourless liquid; νmax (film) inter alia 1630
isomer, only signals at 16.4 (CH C᎐N), 26.5, 29.8 and 31.5
᎐
3
(CH ), 47.5 ((CH ) N), 169.7 (C᎐N) identifiable as (Z)-isomer;
᎐
2
3 2
m/z (FAB) 199 (M ϩ H)ϩ. Anal. Calculated for C12H26N2:
C, 72.7; H, 13.2: N, 14.1. Found: C, 72.4; H, 13.5; N, 14.4%.
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)undecan-3-one
8e
(C᎐N) cmϪ1; δH (CDCl3), E:Z ratio 92:8, (E)-isomer 1.04
The alkylation of hydrazone 5e by iodomethylboronate ester 6,
was carried out by the procedure described for the preparation
of boronate ester 8d on a 28 mmol scale with respect to the
hydrazone component. Dissolving the crude hydrazone 7e in
tetrahydrofuran (150 ml) at room temperature was followed by
addition of aqueous copper() acetate (10 ml of 5.0 M solution,
50 mmol) and the solution was stirred for 12 hours. The tetra-
hydrofuran was removed by rotary evaporation and saturated
ammonium chloride was added to the aqueous solution.
Partitioning the solution between chloroform and saturated
ammonium chloride, and washing the organic phase with a
saturated sodium bicarbonate solution, gave a dark brown oil
after drying the organic phase (MgSO4) and rotary evapor-
ation. Kugelrohr distillation (120 ЊC, 0.5 mmHg) of this residue
removed unreacted iodomethylboronate ester 6 and decan-2-
one. The residue was further purified by flash chromatography
(neat chloroform as eluant) to furnish the boronate ester
8e (2.56 g, 8.6 mmol, 35%) as an orange oil that solidified to a
waxy solid on standing; mp 35 ЊC; νmax (film) inter alia 1715
᎐
(6 H, d, J = 6.9 Hz, (CH ) CH), 1.86 (3 H, s, CH C᎐N), 2.40
᎐
3
3
2
(6 H, s, (CH3)2N), 2.49 (1 H, septet, J = 6.9 Hz, (CH3)2CH);
(Z)-isomer 1.03 (6 H, d, J = 7.2 Hz, (CH3)2CH), 1.82 (3 H, s,
CH C᎐N), 2.39 (6 H, s, (CH ) N), (CH ) CH coincident with
᎐
3
3
2
3 2
(E)-isomer signal; δ (CDCl ) (E)-isomer, 12.5 (CH C᎐N), 19.7
᎐
3
C
3
((CH ) CH), 36.6 ((CH ) CH), 46.6 ((CH ) N), 171.4 (C᎐N);
᎐
3
2
3
2
3 2
(Z)-isomer, 17.5 (CH C᎐N), 19.4 ((CH ) CH), 28.1 ((CH ) -
᎐
3
3
2
3 2
CH), 47.5 ((CH ) N), 174.1 (C᎐N); m/z (EI) 128 (Mϩ), 84
᎐
3
2
(M Ϫ C2H6N)ϩ, 44 (C2H6N) base peak. Anal. Calculated for
C7H16N2: C, 65.6; H, 12.6; N, 21.8. Found: C, 65.5; H, 12.9; N,
22.0%.
4-Methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
pentan-3-one 8d
To a vigorously stirred solution of diisopropylamine (2.38 ml,
17.0 mmol) in tetrahydrofuran (50 ml) at 0 ЊC under argon was
added butyllithium (6.78 ml, 2.5 M in hexanes, 17.0 mmol).
After 20 minutes, hydrazone 5d (1.98 g, 15.4 mmol) was added
dropwise and the temperature maintained at 0 ЊC for a further
hour, the formation of a yellow–cream precipitate occurred
over 20 to 30 minutes. Cooling the solution to Ϫ78 ЊC, was
followed by addition of iodomethylboronate ester 6 (4.13 g,
15.4 mmol), warming to room temperature after 5 minutes gave
a pale yellow precipitous solution. Quenching the reaction
after 4 hours at room temperature with saturated ammonium
chloride was followed by partition between ethyl acetate and
consecutively, saturated ammonium chloride and aqueous
hydrochloric acid (30 ml of a 0.5 M solution, 15 mmol). The
organic phase was dried (MgSO4), and the solvent removed
by rotary evaporation to effect a pale yellow oil; Kugelrohr
distillation of this residue (0.5 mmHg, 90 ЊC) furnished the
boronate ester 8d (1.78 g, 7.9 mmol, 51%) as a colourless oil;
(C᎐O) cmϪ1; δH (CDCl3) 0.87 (3 H, t, J = 7.0 Hz, CH2CH3), 0.90
᎐
(2 H, t, J = 7.1, CH2B), 1.23 (12 H, s, 2 × (CH3)2CO), 1.26 (12
H, br s, (CH ) ), 2.37 (2H, t, J = 7.4 Hz, n-heptCH C᎐O), 2.55
᎐
2
2
6
(2 H, t, J = 7.1 Hz, CH BCH C᎐O); δ (CDCl ) ~5 (br, CH B),
᎐
2
2
C
3
2
14.0 (CH3CH2), 24.7 ((CH3)2CO), 22.6, 24.1, 29.1, 29.2, 29.3,
31.8, 37.4 and 42.2 (CH ), 82.96 ((CH ) CO), 211.6 (C᎐O);
᎐
2
3 2
m/z (FAB) 297 (M ϩ H)ϩ, 197 (M Ϫ C6H11O)ϩ base peak; high
resolution mass spectrum, calculated for C17H34BO3 (M ϩ H)ϩ
297.2601, found 297.2595. Anal. Calculated for C17H33BO3:
C, 68.9; H, 11.2: B, 3.6. Found: C, 69.2; H, 11.5; B, 4.0%.
Acetophenone O-methyloxime 10a
The procedure of Beak et al.8 was followed on a 0.080 mol scale,
affording acetophenone O-methyloxime 10a (11.40 g, 0.076
mol, 96%) as a colourless liquid upon distillation from calcium
hydride; bp 118 ЊC, 20 mmHg (lit.,23 73–73 ЊC, 2.2 mmHg); 1H
NMR and IR spectral data were as reported in the literature;8
νmax (film) inter alia 1718 (C᎐O) cmϪ1; δB (CDCl3) ϩ33.7;
᎐
δH (CDCl3) 0.90 (2 H, t, J = 7.1 Hz, CH2B), 1.08 (6 H, d,
J = 6.9 Hz, (CH3)2CH), 1.23 (12 H, s, 2 × (CH3)2CO), 2.60 (3 H,
septet/triplet exactly superimposed, J = 7.0 Hz, CH(CH3)2
δC (75.5 MHz; CDCl ) 12.5 (CH C᎐N), 61.8 (OCH ), 125.9,
᎐
3
3
3
and CH C᎐O); δ (CDCl3) ~5 (br, CH2B), 18.4 ((CH3)2CH),
128.5, 128.9, 135.8 (C aromatic), 149.7 (C᎐N); m/z (FAB)
᎐
᎐
2
C
24.7 ((CH ) CO), 35.1 (CH C᎐O), 40.3 ((CH ) CHC᎐O), 83.0
149 Mϩ.
᎐
᎐
3
2
2
3 2
((CH ) CO), 215.2 (C᎐O); m/z (CI) 244 (M ϩ NH )ϩ, 227
᎐
3
2
4
(M ϩ H)ϩ; high resolution mass spectrum, calculated for
C12H23BO3 (M ϩ H)ϩ 227.1819, found 227.1822.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)propiophenone
O-methyloxime 11a
To a vigorously stirred solution of diisopropylamine (3.34 ml,
23.70 mmol) in dry THF (50 ml) at 0 ЊC under argon, butyl-
lithium (9.60 ml of a 2.5 M solution in hexanes, 24.00 mmol)
was slowly added. The solution was stirred at 0 ЊC for 45 min-
utes, then cooled to Ϫ78 ЊC. Acetophenone O-methyloxime 10a
(2.88 ml, 19.70 mmol) was added dropwise and the solution
stirred at Ϫ78 ЊC for 3 hours. 2-(Iodomethyl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane 6 (5.36 g, 20.00 mmol) was then
slowly added to the resulting bright yellow solution. The reac-
tion was allowed to warm to room temperature after 2 hours
and stirred overnight. A clear, pale yellow solution was formed
to which 1% HCl (aq) (50 ml) was added. The solution was
quickly extracted with ethyl acetate (3 × 25 ml). The combined
Decan-2-one N,N-dimethylhydrazone 5e
Glacial acetic acid (~0.1 ml) was introduced to a stirred solu-
tion of N,N-dimethylhydrazine (30 ml, 0.395 mol) and decan-2-
one (17.00 g, 0.109 mol), and refluxed for an hour. After remov-
ing the aqueous layer, the solution was refluxed for a further 11
hours, whereupon the cooled solution was partitioned between
diethyl ether and water. Drying the organic phase (MgSO4) gave
a pale yellow oil after rotary evaporation. Distillation under
vacuum (114 ЊC at 0.5 mmHg) through a Vigreux column
furnished the pure hydrazone 5e (18.25 g, 0.092 mol, 84%) as
colourless oil; νmax (film) inter alia 1640 (C᎐N) cmϪ1; δH (CD-
Cl3), E:Z 81:19, (E)-isomer, 0.86 (3 H, t, CH3CH2), 1.25 (10 H,
᎐
3256
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263

View Article Online
organic phases were washed with water (50 ml), dried and
evaporated, yielding boronate ester 11a (4.67 g, 16.00 mmol,
82%) as a very pale yellow oil, after distillation using a Kugel-
rohr apparatus (100 ЊC, 0.5 mmHg) (Found: C, 66.4; H, 8.4;
B, 3.7; N, 4.9. C16H24BNO3 requires C, 66.5; H, 8.4; B, 3.7;
N, 4.8%); νmax (film)/cmϪ1 3000, 2800, 1370, 1320, 1140, 1040;
δH (300 MHz; CDCl3) 0.99–1.05 (2 H, m, CH2B), 1.22 [12 H,
ml), then brine (50 ml), and dried. The solvent was carefully
removed by rotary evaporation under atmospheric pressure.
The colourless liquid residue was fractionally distilled from
calcium hydride. Butan-2-one O-methyloxime 10c (3.53 g, 0.035
mol, 79%) was collected as a colourless liquid; bp 90–94 ЊC, 760
mmHg (lit.,23 66.2 ЊC, 301 mmHg); νmax (film)/cmϪ1 2900, 2800,
1640 (m), 1450, 1350, 1050; δH (300 MHz; CDCl3) E:Z, 3:1,
s, 2 × (CH ) C], 2.77–2.82 (2 H, m, CH C᎐N), 3.96 (3 H, s,
E-isomer: 1.08 (3 H, t, J 7.6, CH CH ), 1.82 (3 H, s, CH C᎐N),
᎐
3 2 3
᎐
3
2
2
OCH3), 7.30–7.39 (3 H, m, H meta, H para), 7.59–7.64 (2 H, m,
H ortho); δC (75.5 MHz; CDCl3) 8.0–8.6 (br, CH2B), 20.8
2.19 (2 H, q, J 7.5, CH C᎐N), 3.83 (3 H, s, OCH ); Z-isomer:
᎐
2 3
1.04 (3 H, t, J 7.7, CH CH ), 1.85 (3 H, s, CH C᎐N), 2.32 (2 H,
᎐
3
3
2
(CH C᎐N), 24.6 [(CH ) C], 61.6 (OCH ), 82.5 [(CH ) C], 126.3,
q, J 7.6, CH C᎐N), 3.81 (3 H, s, OCH ); δ (75.5 MHz; CDCl ),
᎐
2 3 C 3
᎐
2
3
2
3
3
2
128.1, 128.6, 135.4 (C aromatic), 160.0 (C᎐N); δ (64.2 MHz;
E-isomer: 11.0 (CH CH ), 13.3 (CH C᎐N), 29.0 (CH C᎐N),
᎐ ᎐
3 2 3 2
60.9 (OCH ), 158.6 (C᎐N); Z-isomer: 10.0 (CH CH ), 19.1
᎐
3 3 2
᎐
B
CDCl3) ϩ33.6; m/z (FAB) 290 (M ϩ H)ϩ [Found (HRMS): m/z
289.1851. C16H24BNO3 requires Mϩ 289.1849].
(CH C᎐N), 22.2 (CH C᎐N), 60.9 (OCH ), 159.3 (C᎐N); m/z
᎐
᎐
᎐
3
2
3
(EI) 101 Mϩ [Found (HRMS): m/z 101.0838. C5H11NO requires
Mϩ 101.0840].
Acetone O-methyloxime 10b
Acetone (4.19 ml, 0.057 mol) was added to methoxylamine
hydrochloride (4.00 g, 0.048 mol) in pyridine (5 ml) and
dichloromethane (20 ml). The solution was heated at reflux
overnight, then partitioned between dichloromethane and sat-
urated NaCl (aq). The combined organic extracts were washed
with 10% HCl (aq) (50 ml), saturated NaHCO3 (aq) (50 ml),
then brine (50 ml), and dried. Careful evaporation of the
solvent and fractional distillation, under argon, from calcium
hydride of the residue, furnished acetone O-methyloxime 10b
(1.20 g, 0.014 mol, 29%) as a colourless liquid; bp 64–66 ЊC,
760 mmHg (lit.,24 60–65 ЊC, 760 mmHg); νmax (film)/cmϪ1 2925,
2880, 1610 (w), 1410, 1360, 1040, 1020; 1H NMR was identical
to that reported in the literature;24 δC (75.5 MHz; CDCl3) 15.3
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pentan-3-one
O-methyloxime 11c
To a vigorously stirred solution of diisopropylamine (2.10 ml,
14.90 mmol) in dry THF (20 ml) at 0 ЊC under an argon atmos-
phere, butyllithium (6.00 ml of a 2.5 M solution in hexanes,
15.00 mmol) was slowly introduced. The solution was stirred
for 45 minutes and then cooled to Ϫ40 ЊC. Addition of butan-2-
one O-methyloxime 10c (1.48 ml, 12.30 mmol) and stirring for a
further 90 minutes afforded a yellow solution. The reaction was
then cooled to Ϫ78 ЊC and 2-(iodomethyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane 6 (4.96 g, 18.50 mmol) added dropwise.
After 1 hour the reaction was allowed to warm to room tem-
perature and stirred overnight. Addition of 1% HCl (aq) (20
ml) to the pale yellow solution formed was rapidly followed by
extraction with ethyl acetate (3 × 20 ml). The combined organic
phases were washed with water (50 ml) and dried. Evaporation
of the solvent afforded a dark orange oil which was purified
by distillation using a Kugelrohr apparatus (100 ЊC, 0.5
mmHg), furnishing 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)pentan-3-one O-methyloxime 11c (2.35 g, 9.75 mmol, 79%)
as a colourless oil; νmax (film)/cmϪ1 2900, 2800, 1380, 1330,
1160, 1060; δH (300 MHz; CDCl3) 0.94–0.99 (2 H, m, CH2B),
1.07 (3 H, t, J 7.4, CH3CH2), 1.25 [12 H, s, 2 × (CH3)2C], 2.20
(2 H, q, J 7.5, CH3CH2), 2.32–2.37 (2 H, m, CH2CH2B), 3.79
(3 H, s, OCH3); δC (75.5 MHz; CDCl3) 6.8–8.0 (br, CH2B), 11.2
(CH3CH2), 21.9 (CH2CH2B), 24.8 [(CH3)2C], 26.9 (CH3CH2),
(syn CH ), 21.8 (anti CH ), 61.0 (OCH ), 154.6 (C᎐N); m/z (CI,
᎐
3
3
3
NH3) 88 (M ϩ H)ϩ.
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-one
O-methyloxime 11b
To a stirred solution of diisopropylamine (0.18 ml, 1.27 mmol)
in dry THF (15 ml) at 0 ЊC under argon, butyllithium (0.51 ml
of a 2.5 M solution in hexanes, 1.275 mmol) was added slowly.
After 30 minutes the solution was cooled to Ϫ40 ЊC and treated
with acetone O-methyloxime 10b (0.10 g, 1.15 mmol). The reac-
tion was cooled to Ϫ78 ЊC after 90 minutes and 2-(iodomethyl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane 6 (0.46 g, 1.73 mmol)
was added dropwise. The reaction was allowed to warm to
room temperature after 1 hour and stirred overnight. A pale
yellow solution was formed to which 1% HCl (aq) (10 ml) was
added. The mixture was then quickly extracted with ethyl acet-
ate (3 × 10 ml). The combined organic extracts were washed
with water (50 ml), dried and evaporated to yield the crude title
compound 11b (0.21 g, 0.92 mmol, 80%) as a yellow oil; νmax
(film)/cmϪ1 2970, 1370, 1310, 1140, 1050; δH (300 MHz; CDCl3)
1:3, mixture of stereoisomers, major stereoisomer: 0.92–0.98
(2 H, m, CH2B), 1.25 [12 H, s, 2 × (CH3)2C], 1.85 (3 H, s,
60.9 (OCH ), 83.1 [(CH ) C], 163.6 (C᎐N); δ (64.2 MHz;
᎐
3
3
2
B
CDCl3) ϩ33.0; m/z (FAB) 242 (M ϩ H)ϩ [Found (HRMS):
m/z 241.1846. C12H24BNO3 requires Mϩ 241.1849].
Pentan-2-one O-methyloxime 10d
Pentan-2-one (4.68 ml, 0.044 mol) was added to methoxylamine
hydrochloride (4.00 g, 0.048 mol) in pyridine (5 ml) and
dichloromethane (20 ml). The mixture was refluxed overnight,
then partitioned between dichloromethane and saturated NaCl
(aq). The combined organic extracts were washed with 10%
HCl (aq) (50 ml), saturated NaHCO3 (aq) (50 ml), then brine
(50 ml), and dried. Careful evaporation of the solvent and
distillation, under Ar, over calcium hydride, of the residue, fur-
nished pentan-2-one O-methyloxime 10d (3.13 g, 0.027 mmol,
62%) as a colourless liquid; bp 118 ЊC, 760 mmHg (lit.,25 118–
120 ЊC, 760 mmHg); νmax (film)/cmϪ1 2900, 2800, 1630 (m),
1460, 1360, 1050; δH (300 MHz; CDCl3) E:Z, 3:1, E-isomer:
0.92 (3 H, t, J 7.4, CH3CH2), 1.53 (2 H, sextet, J 7.6, CH3CH2),
CH C᎐N), 2.35–2.41 (2 H, m, CH C᎐N), 3.79 (3 H, s, OCH );
᎐
᎐
3
2
3
minor stereoisomer: 0.92–0.98 (2 H, m, CH2B), 1.24 [12 H, s,
2 × (CH ) C], 1.81 (3 H, s, CH C᎐N), 2.25–2.31 (2 H, m,
᎐
3
3
2
CH C᎐N), 3.81 (3 H, s, OCH ); δ (100.6 MHz; CDCl ) 7.4 (br,
᎐
2
3
C
3
CH B), 19.3 (CH C᎐N), 23.2 (CH C᎐N), 24.7 [(CH ) C], 60.8
᎐
᎐
2
3
2
3 2
(OCH ), 82.9 [(CH ) C], 159.6 (C᎐N); δ (64.2 MHz; CDCl3)
᎐
3
3
2
B
ϩ33.7; m/z (CI, NH3) 228 (M ϩ H)ϩ [Found (HRMS): m/z
228.1775. C11H22BNO3 requires (M ϩ H)ϩ 228.1771].
Butan-2-one O-methyloxime 10c
1.81 (3 H, s, CH C᎐N), 2.10–2.16 (2 H, m, CH C᎐N), 3.83 (3 H,
᎐
᎐
2
3
Butan-2-one (3.94 ml, 0.044 mol) was added to methoxyl-
amine hydrochloride (4.00 g, 0.048 mol) in pyridine (5 ml) and
dichloromethane (20 ml), and the solution heated at reflux for
16 hours. A biphasic mixture was formed which was diluted
with saturated NaCl (aq) (50 ml), and extracted with dichloro-
methane (3 × 20 ml). The combined organic extracts were
washed with 10% HCl (aq) (50 ml), saturated NaHCO3 (aq) (50
s, OCH3); Z-isomer: 0.93 (3 H, t, J 7.4, CH3CH2), 1.53 (2 H,
sextet, J 7.6, CH CH ), 1.84 (3 H, s, CH C᎐N), 2.26–2.31 (2 H,
᎐
3
3
2
m, CH C᎐N), 3.80 (3 H, s, OCH ); δ (75.5 MHz, CDCl3)
᎐
2
3
C
E-isomer: 13.5 (CH C᎐N), 19.8 (CH CH ), 31.0 (CH C᎐N),
᎐
᎐
2
3
3
2
37.6 (CH CH ), 60.9 (OCH ), 157.6 (C᎐N); Z-isomer: 14.0
᎐
3
2
3
(CH C᎐N), 19.0 (CH CH ), 31.0 (CH C᎐N), 37.6 (CH CH ),
᎐
᎐
3
3
2
2
3
2
60.9 (OCH ), 158.0 (C᎐N); m/z (CI, NH ) 116 (M ϩ H)ϩ.
᎐
3
3
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
3257

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1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-3-one
O-methyloxime 11d
and the combined organic extracts washed with water (50 ml),
then dried. Evaporation of the solvent and distillation of the
residue using a Kugelrohr apparatus (100 ЊC, 0.5 mmHg),
yielded the title compound 11e (1.50 g, 5.88 mmol, 48%) as a
colourless oil; νmax (film)/cmϪ1 3050, 2980, 1370, 1265, 1145,
1050; δH (300 MHz; CDCl3) 0.97–1.02 (2 H, m, CH2B), 1.08
[6 H, d, J 6.9, (CH3)2CH], 1.25 [12 H, s, 2 × (CH3)2CO], 2.24–
Butyllithium (0.60 ml of a 2.5 M solution in hexanes, 1.50
mmol) was added to a vigorously stirred solution of diiso-
propylamine (0.21 ml, 1.49 mmol) in THF (20 ml) at 0 ЊC under
an argon atmosphere. After 45 minutes the reaction was cooled
to Ϫ40 ЊC, and pentan-2-one O-methyloxime 10d (0.14 g, 1.22
mmol) was slowly introduced. The solution was stirred for a
further 2.5 hours yielding a pale yellow solution. The reaction
was then cooled to Ϫ78 ЊC and 2-(iodomethyl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane 6 (0.50 g, 1.87 mmol) was slowly
added. After 2 hours the reaction was left to warm to room
temperature overnight. 1% HCl (aq) (20 ml) was added to the
yellow solution formed, and the mixture extracted with ethyl
acetate (3 × 20 ml). The combined organic phases were washed
with water (50 ml) and dried. Evaporation of the solvent
yielded an orange oil. Distillation using a Kugelrohr apparatus
(100 ЊC, 0.5 mmHg) furnished the β-boronate oxime ether
derivative 11d (0.20 g, 0.78 mmol, 64%) as a colourless oil;
νmax (film)/cmϪ1 2900, 2800, 1625 (w), 1360, 1320, 1140, 1040;
δH (300 MHz; CDCl3) 0.91 (3 H, t, J 7.4, CH3CH2), 0.93–0.98
(2 H, m, CH2B), 1.24 [12 H, s, 2 × (CH3)2C], 1.52 (2 H, sextet,
J 7.5, CH3CH2), 2.11–2.16 (2 H, m, CH3CH2CH2), 2.30–2.36
(2 H, m, CH2CH2B), 3.80 (3 H, s, OCH3); δC (75.5 MHz;
CDCl3) 7.5–7.7 (br, CH2B), 13.6 (CH3CH2), 19.8 (CH3CH2),
2.30 (2 H, m, CH C᎐N), 2.49 [1 H, septet, J 6.9, (CH ) CH],
᎐
2
3 2
3.79 (3 H, s, OCH3); δC (75.5 MHz; CDCl3) 8.3 (br, CH2B), 20.1
[(CH ) CH], 20.8 (CH C᎐N), 24.8 [(CH ) CO], 33.3 [(CH ) -
᎐
3
2
2
3
2
3 2
CH], 60.9 (OCH ), 83.1 [(CH ) CO], 166.5 (C᎐N); δ (64.2
᎐
3
3
2
B
MHz; CDCl3) ϩ33.9; m/z (FAB) 256 (M ϩ H)ϩ [Found
(HRMS): m/z 255.2005. C13H26BNO3 requires Mϩ 255.2006].
3,3-Dimethylbutan-2-one O-methyloxime 10f
To a stirred solution of methoxylamine hydrochloride (8.00 g,
0.096 mol) in pyridine (10 ml) and dichloromethane (40 ml),
3,3-dimethylbutan-2-one (13.18 ml, 0.11 mol) was added. The
mixture was refluxed for 16 hours. Saturated NaCl (aq) (50 ml)
was then added and the solution extracted with dichloro-
methane (3 × 25 ml). The combined organic extracts were
washed with 10% HCl (aq) (50 ml), saturated NaHCO3 (aq) (50
ml), then brine (50 ml), and dried. Evaporation of the solvent
and distillation, under Ar, over calcium hydride, of the residue,
yielded the title compound 10f (8.26 g, 0.064 mol, 67%) as a
colourless liquid; bp 122–124 ЊC, 760 mmHg (lit.,23 52.5 ЊC,
56 mmHg); νmax (film)/cmϪ1 2900, 2800, 1625 (m), 1460, 1370,
1050; δH (300 MHz; CDCl3) 1.11 [9 H, s, (CH3)3C], 1.79 (3 H, s,
21.8 (CH2CH2B), 24.4 [(CH3)2C], 35.4 (CH C᎐N), 60.7
᎐
2
(OCH ), 82.9 [(CH ) C], 162.4 (C᎐N); δ (64.2 MHz; CDCl3)
᎐
3
3
2
B
ϩ33.9; m/z (FAB) 256 (M ϩ H)ϩ [Found (HRMS): m/z
256.2084. C13H26BNO3 requires (M ϩ H)ϩ 256.2073].
CH C᎐N), 3.82 (3 H, s, OCH ); δ (75.5 MHz; CDCl3) 10.3
᎐
3
3
C
(CH C᎐N), 27.6 [(CH ) C], 36.9 [(CH ) C], 61.0 (OCH ), 163.2
᎐
3
3
3
3
3
3
(C᎐N); m/z (EI) 129 Mϩ [Found (HRMS): m/z 129.1147.
3-Methylbutan-2-one O-methyloxime 10e
᎐
C7H15NO requires Mϩ 129.1153].
3-Methylbutan-2-one (4.60 ml, 0.043 mol) was added to a solu-
tion of methoxylamine hydrochloride (4.00 g, 0.048 mol) in
pyridine (5 ml) and dichloromethane (20 ml). Refluxing the
solution overnight yielded a biphasic solution. This solution
was partitioned between saturated NaCl (aq) and dichloro-
methane. The combined organic extracts were washed with 10%
HCl (aq) (50 ml), saturated NaHCO3 (aq) (50 ml) and brine (50
ml), then dried. The solvent was carefully removed by rotary
evaporation, and the residue fractionally distilled under atmos-
pheric pressure from calcium hydride, furnishing 3-methyl-
butan-2-one O-methyloxime 10e (2.17 g, 0.019 mol, 44%) as a
colourless liquid; bp 112 ЊC, 760 mmHg; νmax (film)/cmϪ1 2900,
2800, 1635 (m), 1440, 1340, 1060, 1030; δH (300 MHz; CDCl3)
E:Z, 7.8:1, E-isomer: 1.07 [6 H, d, J 6.9, (CH3)2CH], 1.76 (3 H,
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4,4-dimethyl-
pentan-3-one O-methyloxime 11f
To a vigorously stirred solution of diisopropylamine (3.31 ml,
23.49 mmol) in THF (40 ml) at 0 ЊC under Ar, butyllithium
(9.60 ml of a 2.5 M solution in hexanes, 24.00 mmol) was slowly
added. Stirring for 30 minutes yielded a pale yellow solution.
The reaction was then cooled to Ϫ40 ЊC and 3,3-dimethyl-
butan-2-one O-methyloxime 10f (2.54 g, 19.66 mmol) was
introduced. After 3 hours the reaction temperature was lowered
to Ϫ78 ЊC and 2-(iodomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane 6 (6.32 g, 23.59 mmol) was added dropwise. The mix-
ture was allowed to warm to room temperature after 1 hour,
then stirred overnight, yielding a pale yellow solution. 1% HCl
(aq) (50 ml) was added and the solution extracted with ethyl
acetate (3 × 20 ml). Drying the combined organic extracts and
evaporation of the solvent afforded a yellow oil. Distillation of
this oil using a Kugelrohr apparatus (100 ЊC, 0.5 mmHg)
furnished 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4,4-
dimethylpentan-3-one O-methyloxime 11f (4.20 g, 15.60 mmol,
79%) as a colourless oil; νmax (film)/cmϪ1 2900, 2800, 1360, 1310,
1140, 1040; δH (300 MHz; CDCl3) 0.98–1.04 (2 H, m, CH2B),
s, CH C᎐N), 2.50 [1 H, septet, J 6.9, (CH ) CH], 3.82 (3 H, s,
᎐
3
3 2
OCH3); Z-isomer: 1.01 [6 H, d, J 7.0, (CH3)2CH], 1.77 (3 H,
s, CH C᎐N), 3.35 [1 H, septet, J 7.0, (CH ) CH], 3.80 (3 H, s,
᎐
3
3 2
OCH ); δ (75.5 MHz; CDCl ) E-isomer: 10.5 (CH C᎐N), 19.5
᎐
3
3
C
3
[(CH ) CH], 33.9 [(CH ) CH], 60.7 (OCH ), 161.5 (C᎐N);
᎐
3
2
3
2
3
Z-isomer: 15.0 (CH C᎐N), 18.7 [(CH ) CH], 26.1 [(CH ) CH],
᎐
᎐
3
3
2
3 2
60.7 (OCH ), 162.4 (C᎐N); m/z (EI) 115 Mϩ [Found (HRMS):
3
m/z 115.0988. C6H13NO requires Mϩ 115.0997].
1.10 [9 H, s, (CH ) CC᎐N], 1.25 [12 H, s, 2 × (CH ) CO], 2.24–
᎐
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyl-
pentan-3-one O-methyloxime 11e
3
3
3 2
2.30 (2 H, m, CH C᎐N), 3.79 (3 H, s, OCH ); δ (75.5 MHz;
᎐
2
3
C
CDCl ) 9.2 (br, CH B), 20.1 (CH C᎐N), 24.8 [(CH ) CO], 27.7
᎐
3
2
2
3 2
To a stirred solution of diisopropylamine (2.10 ml, 14.90 mmol)
in THF (20 ml) at 0 ЊC under argon, butyllithium (6.00 ml of a
2.5 M solution in hexanes, 15.00 mmol) was slowly added. After
30 minutes the reaction was cooled to Ϫ40 ЊC and 3-methyl-
butan-2-one O-methyloxime 10e (1.40 g, 12.16 mmol) was
added. The reaction was stirred for 3.5 hours, then cooled to
Ϫ78 ЊC before adding 2-(iodomethyl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane 6 (4.20 g, 15.68 mmol) to the orange solution
formed. After 2 hours, the reaction was allowed to warm to
room temperature, and stirred overnight. A clear yellow solu-
tion was formed to which 1% HCl (aq) (20 ml) was added. The
solution was quickly extracted with ethyl acetate (3 × 20 ml)
[(CH ) C], 37.2 [(CH ) CC᎐N], 59.9 (OCH ), 83.0 [(CH ) CO],
᎐
3
3
3
3
3
3 2
168.1 (C᎐N); δ (64.2 MHz; CDCl3) ϩ33.5; m/z (FAB) 270
᎐
B
(M ϩ H)ϩ [Found (HRMS): m/z 269.2169. C14H28BNO3
requires Mϩ 269.2162].
3-Methylheptan-2-one O-methyloxime 10g
3-Methylheptan-2-one (6.82 ml, 0.044 mol) was added to a
solution of methoxylamine hydrochloride (4.00 g, 0.048 mol) in
pyridine (5 ml) and dichloromethane. The solution was refluxed
overnight. A yellow solution was formed which was diluted
with saturated NaCl (aq) (50 ml) and extracted with dichloro-
3258
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263

View Article Online
methane (3 × 20 ml). The combined organic phases were
washed with 10% HCl (aq) (50 ml), saturated NaHCO3 (aq) (50
ml), then brine (50 ml), and dried. The solvent was evaporated
and the residue distilled under water aspirator vacuum, from
calcium hydride, furnishing the O-methyloxime 10g (3.87 g,
0.025 mol, 56%) as a colourless liquid; bp 28 ЊC, 20 mmHg; νmax
(film)/cmϪ1 2900, 2800, 1630 (m), 1440, 1360, 1340, 1070, 1040;
δH (300 MHz; CDCl3) E:Z, 6:1, E-isomer: 0.88 (3 H, t, J 7.1,
CH3CH2), 1.05 (3 H, d, J 6.9, CH3CH), 1.14–1.51 [6 H, m,
CH C᎐N), 2.26–2.31 (2 H, m, CH C᎐N), 3.80 (3 H, s, OCH );
᎐
᎐
3
2
3
δC (75.5 MHz; CDCl ) E-isomer: 13.6 (CH C᎐N), 14.1
᎐
3
3
(CH3CH2), 22.6, 26.6, 29.2, 31.8, 35.8 (CH2), 61.0 (OCH3),
157.8 (C᎐N); Z-isomer: 14.1 (CH CH ), 19.9 (CH C᎐N), 22.6,
᎐
᎐
2
3
2
25.7, 29.2, 29.6, 31.8 (CH ), 59.9 (OCH ), 158.4 (C᎐N); m/z (EI)
᎐
2
3
185 Mϩ [Found (HRMS): m/z 185.1783. C11H23NO requires Mϩ
185.1780].
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)undecan-3-one
(CH ) CH ], 1.73 (3 H, s, CH C᎐N), 2.35 (1 H, sextet, J 6.9,
O-methyloxime 11h
᎐
3
2
3
3
CH3CH), 3.82 (3 H, s, OCH3); Z-isomer: 0.91 (3 H, t, J 7.2,
CH3CH2), 0.99 (3 H, d, J 7.0, CH3CH), 1.14–1.51 [6 H, m,
To a stirred solution of diisopropylamine (1.24 ml, 8.80 mmol)
in dry THF (40 ml) at 0 ЊC under Ar, butyllithium (3.60 ml of a
2.5 M solution in hexanes, 9.00 mmol) was added dropwise.
After 30 minutes the solution was cooled to Ϫ40 ЊC and decan-
2-one O-methyloxime 10h (1.34 g, 7.23 mmol) was slowly
added. After 2 hours, the bright yellow solution was cooled to
Ϫ78 ЊC, before dropwise addition of 2-(iodomethyl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane 6 (2.40 g, 8.96 mmol). The
reaction was allowed to warm to room temperature overnight.
A clear pale yellow solution was formed to which 1% HCl (aq)
(50 ml) was added. The solution was quickly extracted with
ethyl acetate (3 × 30 ml), and the combined organic phases were
washed with water (50 ml), and dried. Evaporation afforded a
pale orange liquid which was purified by flash chromatography
[1:20, ethyl acetate–petroleum ether (40–60 ЊC) as eluent],
furnishing title compound 11h (1.12 g, 3.44 mmol, 48%) as a
pale yellow oil; νmax (film)/cmϪ1 2990–2860, 1470, 1380, 1320,
1150, 1050; δH (300 MHz; CDCl3) 0.87 (3 H, t, J 6.7, CH3CH2),
0.93–0.99 (2 H, m, CH2B), 1.25 [12 H, s, 2 × (CH3)2C], 1.23–
1.50 [12 H, m, CH3(CH2)6], 2.12–2.17 [2 H, m, (CH2)6-
(CH ) CH ], 1.75 (3 H, s, CH C᎐N), 3.28 (1 H, sextet, J 7.2,
᎐
3
2
3
3
CH3CH), 3.79 (3 H, s, OCH3); δC (75.5 MHz; CDCl3)
E-isomer: 10.2 (CH C᎐N), 13.9 (CH CH ), 18.0 (CH CH),
᎐
3
3
2
3
22.5 (CH3CH2), 29.5 (CH3CH2CH2CH2), 33.6 (CH3CH2-
CH ), 39.2 (CH CH), 60.9 (OCH ), 161.2 (C᎐N); Z-isomer:
᎐
2
3
3
15.2 (CH C᎐N), 17.1 (CH CH ), 18.0 (CH CH), 25.5 (CH -
᎐
3
3
2
3
3
CH2), 26.3 (CH3CH2CH2CH2), 31.5 (CH3CH), 33.3 (CH3CH2-
CH ), 60.9 (OCH ), 162.0 (C᎐N); m/z (CI, NH ) 158 (M ϩ
᎐
2
3
3
H)ϩ [Found (HRMS): m/z 157.1472. C9H19NO requires Mϩ
157.1467].
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyloctan-
3-one O-methyloxime 11g
To a vigorously stirred solution of diisopropylamine (1.24 ml,
8.80 mmol) in dry THF (20 ml) at 0 ЊC under argon, butyl-
lithium (3.60 ml of a 2.5 M solution in hexanes, 9.00 mmol)
was slowly added. After 30 minutes stirring, the reaction was
cooled to Ϫ40 ЊC and 3-methylheptan-2-one O-methyloxime
10g (1.16 g, 7.38 mmol) was introduced dropwise. The reaction
was cooled to Ϫ78 ЊC after 3.5 hours, and 2-(iodomethyl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane 6 (2.40 g, 8.96 mmol)
was added. The yellow solution was allowed to warm to room
temperature after 2 hours. A clear, yellow solution was formed
to which 1% HCl (aq) (20 ml) was added. The solution was
quickly extracted with ethyl acetate (3 × 20 ml) and the com-
bined organic phases washed with water (50 ml), then dried.
Evaporation of the solvent afforded a dark orange oil which
was purified by flash chromatography [1:20, ethyl acetate–
petroleum ether (40–60 ЊC) as eluent], furnishing 1-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyloctan-3-one O-
methyloxime 11g (1.35 g, 4.53 mmol, 61%) as a pale yellow
oil; νmax (film)/cmϪ1 2900, 2800, 1625 (w), 1430, 1350, 1300,
1120, 1030; δH (300 MHz; CDCl3) 0.85–0.89 (2 H, m, CH2B),
1.06 (3 H, d, J 7.0, CH3CH), 1.15–1.36 [18 H, m, 2 × (CH3)2-
CO, CH3(CH2)3], 2.14–2.35 (3 H, m, CH3CH, CH2CH2B), 3.79
(3 H, s, OCH3); δC (75.5 MHz; CDCl3) 7.8–9.3 (br, CH2B), 14.1
(CH3CH2), 18.2 (CH3CH), 20.6 (CH2CH2B), 22.7 (CH3CH2),
24.8 [(CH3)2CO], 29.6 (CH3CH2CH2), 33.8 (CH2CH), 38.9
CH C᎐N], 2.30–2.36 (2 H, m, CH CH B), 3.79 (3 H, s, OCH );
᎐
2
2
2
3
δC (75.5 MHz; CDCl3) 7.4 (br, CH2B), 14.1 (CH3CH2), 22.0
(CH2CH2B), 22.6 (CH3CH2), 24.7 [(CH3)2CO], 26.7, 29.2, 29.3,
29.4, 31.8, 33.7 [(CH ) C᎐N], 60.9 (OCH ), 83.1 [(CH ) CO],
᎐
2
6
3
3 2
162.8 (C᎐N); δ (64.2 MHz; CDCl3) ϩ33.9; m/z (FAB)
᎐
B
326 (M ϩ H)ϩ [Found (HRMS): m/z 325.2785. C18H36BNO3
requires Mϩ 325.2788].
(1S,2S)-1,2-Bis(1-methoxycyclopentyl)ethane-1,2-diol (S,S)-17
10% Palladium-on-charcoal (0.64 g, 0.61 mmol) was added to
a solution of (4S,5S)-4,5-bis(1-methoxycyclopentyl)-2-phenyl-
1,3-dioxolane (S,S)-183a (4.00 g, 0.012 mol) in methanol (250
ml). The mixture was stirred in an autoclave at room temper-
ature under an atmosphere of H2 (1000 psi) for 24 hours. The
solution was then evaporated, the residue redissolved in ethyl
acetate (200 ml), and filtered through a pad of magnesium sul-
fate. Evaporation afforded the title compound (S,S)-17 (2.93 g,
0.011 mol, 95%) as a white solid, which was identical to that
previously reported.3a
(CH CH), 61.0 (OCH ), 83.1 [(CH ) CO], 166.1 (C᎐N); δ (64.2
᎐
3
3
3
2
B
(1R,2R)-1,2-Bis(1-methoxycyclopentyl)ethane-1,2-diol (R,R)-19
MHz; CDCl3) ϩ33.5; m/z (FAB) 298 (M ϩ H)ϩ [Found
(HRMS): m/z 298.2552. C16H33BNO3 requires (M ϩ H)ϩ
298.2553].
The procedure described above was followed on a 0.012 mol
scale using (4R,5R)-4,5-bis(1-methoxycyclopentyl)-2-phenyl-
1,3-dioxolane3a to yield the title compound (R,R)-19 (2.82 g,
0.011 mol, 91%) as a white solid, which was identical to that
previously reported.3a
Decan-2-one O-methyloxime 10h
A solution of decan-2-one (7.58 ml, 0.040 mol) and methoxyl-
amine hydrochloride (4.00 g, 0.048 mol) in pyridine (15 ml)
and methanol (100 ml) was heated at reflux for 24 hours. The
solvent was removed by rotary evaporation and the residue par-
titioned between water and diethyl ether. The combined organic
phases were dried and evaporated. Distillation yielded decan-2-
one O-methyloxime 10h (4.01 g, 0.022 mol, 54%) as a colourless
liquid; bp 138–140 ЊC, 20 mmHg; νmax (film)/cmϪ1 2995, 2927,
2856, 2815, 1466, 1440, 1115, 1057; δH (300 MHz; CDCl3) E:Z,
2.7:1, E-isomer: 0.87 (3 H, t, J 6.7, CH3CH2), 1.27–1.50 (12 H,
(4S,5S)-2-Chloromethyl-4,5-bis(1-methoxycyclopentyl)-1,3,2-
dioxaborolane (S,S)-20
To a stirred solution of bromochloromethane (0.19 ml, 2.84
mmol) and trimethyl borate (0.27 ml, 2.38 mmol) in THF (10
ml) at Ϫ78 ЊC under argon, butyllithium (0.96 ml of a 2.5 M
solution in hexanes, 2.40 mmol) was added dropwise. After two
hours the reaction was quenched with chlorotrimethylsilane
(0.34 ml, 2.68 mmol) and allowed to warm to room temperature
overnight. A colourless solution and white precipitate were
formed, to which diol (S,S)-17 (0.31 g, 1.20 mmol) dissolved in
diethyl ether (5 ml) was added. After stirring the solution for 90
m, (CH ) CH ), 1.81 (3 H, s, CH C᎐N), 2.12–2.17 (2 H, m,
᎐
3
2
6
3
CH C᎐N), 3.84 (3 H, s, OCH ); Z-isomer: 0.87 (3 H, t, J 6.7,
᎐
2
3
CH3CH2), 1.27–1.50 [12 H, m, (CH2)6CH3], 1.84 (3 H, s,
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
3259

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minutes, the mixture was partitioned between water and diethyl
ether. The organic phases were dried, filtered and evaporated to
yield a pale yellow oil. Impurities were removed by distillation
using a Kugelrohr apparatus (100 ЊC, 0.5 mmHg,), yielding the
title compound (S,S)-20 (0.36 g, 1.14 mmol, 95%) as a pale
yellow oil; [α]D26 ϩ56 (c 1.075, CHCl3); νmax (film)/cmϪ1 3000–
2820, 1390, 1355, 1090–1070, 901; δH (300 MHz; CDCl3) 1.57–
1.80 (16 H, m, CH2 cyclopentyl), 3.01 (2 H, s, CH2Cl), 3.25
(6 H, s, 2 × OCH3), 4.40 (2 H, s, 2 × CHO); δC (75.5 MHz;
CDCl3) 24.5, 30.6, 31.3 (CH2 cyclopentyl), 50.4 (OCH3),
82.0 (CHO), 87.6 (COCH3); δB (64.2 MHz; CDCl3) ϩ32.1;
m/z (FAB) 317 (M ϩ H)ϩ [Found (HRMS): m/z 317.1691.
C15H26BClO4 requires (M ϩ H)ϩ 317.1690].
ethyl acetate–petroleum ether (40–60 ЊC) as eluent] yielded the
title compound (S,S)-23 (0.040 g, 0.093 mmol, 21%) as a col-
ourless oil; [α]D24 ϩ33.0 (c 0.0485, MeOH); νmax (film)/cmϪ1 3050,
2990–2920, 1420, 1360, 1050; δH (300 MHz; CDCl3) 1.06–1.11
(2 H, m, CH2B), 1.53–1.82 (16 H, m, CH2 cyclopentyl), 2.77–
2.83 (2 H, m, CH2CH2B), 3.24 (6 H, s, 2 × COCH3), 3.96 (3 H,
s, NOCH3), 4.31 (2 H, s, 2 × CHO), 7.32–7.37 (3 H, m, H meta,
H para) and 7.58–7.62 (2 H, m, H ortho); δC (75.5 MHz; CDCl3)
7.6 (br, CH2B), 20.7 (CH2CH2B), 24.4, 24.6, 30.6, 31.2 (CH2
cyclopentyl), 50.3 (COCH3), 61.7 (NOCH3), 80.7 (CHO),
87.7 (COCH3), 126.2, 128.2, 128.7, 135.4 (C aromatic), 159.9
(C᎐N); δ (64.2 MHz; CDCl3) ϩ33.1; m/z (FAB) 430 (M ϩ
᎐
B
H)ϩ [Found (HRMS): m/z 430.2775. C24H36BNO5 requires
(M ϩ H)ϩ 430.2765].
(4S,5S)-2-Iodomethyl-4,5-bis(1-methoxycyclopentyl)-1,3,2-
dioxaborolane (S,S)-15
3-(1,3,6,2-Dioxazaborocan-2-yl)propiophenone O-methyloxime
24
To a stirred solution of chloromethylboronate ester (S,S)-20
(0.13 g, 0.41 mmol) in acetone (2 ml), sodium iodide (0.070 g,
0.47 mmol) in acetone (3 ml) was added. A creamy yellow solu-
tion was formed which was stirred at ambient temperature for
24 hours. The solution was filtered through a glass sinter, and
the solvent evaporated. Petroleum ether (40–60 ЊC) (10 ml) was
added to the orange residue. Additional filtration yielded the
title compound (S,S)-15 (0.16 g, 0.39 mmol, 96%) as an orange
oil after evaporation; [α]D26 ϩ41 (c 1.91, CHCl3); νmax (film)/cmϪ1
3000–2820, 1410, 1385, 1340, 1090–1070, 920; δH (300 MHz;
CDCl3) 1.64–1.82 (16 H, m, CH2 cyclopentyl), 2.22 (2 H,
s, CH2I), 3.24 (6 H, s, 2 × OCH3), 4.39 (2 H, s, 2 × CHO);
δC (75.5 MHz; CDCl3) 8.9–9.3 (br, CH2B), 24.6, 30.7, 31.2
(CH2 cyclopentyl), 50.3 (OCH3), 81.4 (CHO), 87.9 (COCH3);
δB (64.2 MHz; CDCl3) ϩ31.9; m/z (FAB) 409 (M ϩ H)ϩ
[Found (HRMS): m/z 409.1048. C15H26BIO4 requires (M ϩ H)ϩ
409.1049].
To a solution of boronate ester 11a (4.67 g, 0.016 mol) in diethyl
ether (30 ml), diethanolamine (8.00 ml of a 2.0 M solution in
propan-2-ol, 0.016 mol) was added dropwise. Refrigeration of
the resulting milky solution yielded the title compound 24 (2.67
g, 9.67 mmol, 60%) as a white amorphous solid, after filtration
and drying under vacuum over P2O5; mp 175–176 ЊC; νmax
(KBr)/cmϪ1 3050, 2980, 1420, 1365; δH (300 MHz; CDCl3) 0.76
(2 H, t, J 7.8, CH2B), 2.65 (2 H, t, J 7.8, CH2CH2B), 2.79–2.82
(2 H, m, CH2NH), 3.21–3.30 (2 H, m, CH2NH), 3.87–3.91 (2 H,
m, CH2O), 4.00 (3 H, s, OCH3), 3.98–4.06 (2 H, m, CH2O), 4.89
(1 H, br s, NH), 7.32–7.37 (3 H, m, H meta, H para), 7.66–7.70
(2 H, m, H ortho) [After treatment with D2O, 1.4:1 mixture of
stereoisomers, major diastereomer: 0.65–0.70 (2 H, m, CH2B),
2.60–2.65 (2 H, m, CH2CH2B), 2.69–2.76 (2 H, m, CH2ND),
3.14–3.23 (2 H, m, CH2ND), 3.78–3.85 (2 H, m, CH2O), 3.90–
3.98 (2 H, m, CH2O), 3.95 (3 H, s, OCH3), 7.31–7.37 (3 H, m, H
meta, H para), 7.60–7.68 (2 H, m, H ortho); minor diastereo-
mer: 1.05 (2 H, t, J 7.6, CH2B), 2.69–2.76 (2 H, m, CH2ND),
2.82 (2 H, t, J 7.6, CH2CH2B), 3.14–3.23 (2 H, m, CH2ND),
3.78–3.85 (2 H, m, CH2O), 3.90–3.98 (2 H, m, CH2O), 4.00
(3 H, s, OCH3), 7.31–7.37 (3 H, m, H meta, H para), 7.60–7.68
(2 H, m, H ortho)]; δC (75.5 MHz; CDCl3) 15.0 (br, CH2B), 22.3
(CH2CH2B), 51.4 (CH2NH), 61.5 (OCH3), 62.6 (CH2O), 126.5,
(4R,5R)-2-Chloromethyl-4,5-bis(1-methoxycyclopentyl)-1,3,2-
dioxaborolane (R,R)-21
The procedure described for 20 was followed on a 1.20 mmol
scale using diol (R,R)-19, affording chloromethylboronate ester
(R,R)-21 (0.344 g, 1.09 mmol, 91%); [α]D26 Ϫ50 (c 0.82, CHCl3);
all other spectrometric data were identical to those reported for
compound (S,S)-20.
128.2, 128.7, 135.7 (C aromatic), 162.8 (C᎐N); δ (64.2 MHz;
᎐
B
CDCl3) ϩ12.5; m/z (FAB) 277 (M ϩ H)ϩ [Found (HRMS): m/z
276.1637. C14H21BN2O3 requires Mϩ 276.1645].
(4R,5R)-2-Iodomethyl-4,5-bis(1-methoxycyclopentyl)-1,3,2-
dioxaborolane (R,R)-22
3-[(4R,5R)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-
2-yl]propiophenone O-methyloxime (R,R)-25
The procedure used was identical to that used for 15, on a 0.80
mmol scale using chloromethylboronate ester (R,R)-21, yield-
ing iodide (R,R)-22 (0.32 g, 0.78 mmol, 98%); [α]D26 Ϫ37 (c 0.96,
CHCl3); all other spectrometric data were identical to those
reported for compound (S,S)-15.
To a solution of diethanolamine derivative 24 (0.96 g, 3.48
mmol) and diol (R,R)-19 (0.90 g, 3.48 mmol) in chloroform (50
ml), HCl (aq) (87.00 ml of a 0.040 M solution, 3.48 mmol) was
added. The biphasic solution was stirred vigorously for 1 hour
at room temperature. The organic layer was separated,
washed with water (50 ml) and dried. Filtration and evaporation
yielded the title compound (R,R)-25 (1.35 g, 3.14 mmol, 90%)
as a colourless oil; [α]D24 Ϫ33.4 (c 0.8615, MeOH); all other
spectroscopic and analytical properties were identical to those
obtained for compound (S,S)-23.
3-[(4S,5S)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-
2-yl]propiophenone O-methyloxime (S,S)-23
To a stirred solution of diisopropylamine (0.070 ml, 0.50 mmol)
at 0 ЊC in dry THF (5 ml), butyllithium (0.24 ml of a 2.5 M
solution in hexanes, 0.60 mmol) was slowly added. After 30
minutes the pale yellow solution was cooled to Ϫ78 ЊC and
acetophenone O-methyloxime 10a (0.066 ml, 0.45 mmol) was
added dropwise. A bright yellow solution was formed which
was stirred for a further 2.5 hours, after which time, a solution
of (4S,5S)-2-iodomethyl-4,5-bis(1-methoxycyclopentyl)-1,3,2-
dioxaborolane (S,S)-15 (0.20 g, 0.49 mmol) in THF (0.50 ml)
was slowly added. The reaction was maintained at Ϫ78 ЊC for a
further 1 hour. The solution was then allowed to warm to room
temperature overnight. A clear yellow solution was formed to
which 1% HCl (aq) (5 ml) was added. The solution was quickly
extracted with ethyl acetate (3 × 10 ml). The combined organic
phases were washed with water (20 ml), dried and evaporated to
furnish a pale orange oil. Flash column chromatography [1:25,
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4,4-dimethyl-
pentan-3-one 8f
To a solution of 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-4,4-dimethylpentan-3-one O-methyloxime 11f (0.086 g, 0.32
mmol) in acetone (3 ml) and water (0.3 ml), paraformaldehyde
(0.15 g) and Amberlyst 15 (0.10 g) were added. The mixture was
stirred at room temperature for 24 hours, then the insoluble
materials were removed by filtration. The solvent was removed
and the resulting cloudy residue was dissolved in diethyl ether
(10 ml), washed with saturated NaCl (aq) (20 ml), dried and
evaporated to yield the title compound 8f (0.072 g, 0.30 mmol,
3260
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263

View Article Online
94%) as a very pale yellow oil; νmax (film)/cmϪ1 3000–2850, 1695,
1380–1360, 1140, 1070; δH (300 MHz; CDCl3) 0.88 (2 H, t, J 6.9,
CH2B), 1.13 [9 H, s, (CH3)3C], 1.23 [12 H, s, 2 × (CH3)2CO],
3-[(4S,5S)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-2-
yl]propiophenone 2
The procedure outlined for the conversion of 11f to 8f was
followed on a 2.20 mmol scale using 3-[(4S,5S)-4,5-bis(1-
methoxycyclopentyl)-1,3,2-dioxaborolan-2-yl]propiophenone
O-methyloxime (S,S)-23 to afford the title compound ketone
(S,S)-2 (0.331 g, 0.83 mmol, 37%) as a colourless oil after
column chromatography [1:20, ethyl acetate–petroleum ether
(40–60 ЊC) as eluent], which was identical to that reported
previously.3a
2.65 (2 H, t, J 7.0, CH C᎐O); δ (75.5 MHz; CDCl3) 24.7
᎐
2
C
[(CH ) CO], 26.6 [(CH ) C], 31.7 (CH C᎐O), 43.6 [(CH ) C],
᎐
3
2
3
3
2
3 3
82.9 [(CH ) CO], 216.6 (C᎐O); δ (64.2 MHz; CDCl3) ϩ33.5;
᎐
3
2
B
m/z (FAB) 241 (M ϩ H)ϩ [Found (HRMS): m/z 241.1971.
C13H25BO3 requires (M ϩ H)ϩ 241.1975].
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pentan-3-one 8b
The procedure outlined for the conversion of 11f to 8f was
followed on a 1.20 mmol scale using 1-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)pentan-3-one O-methyloxime 11c to
yield ketone 8b (0.20 g, 0.94 mmol, 79%) as a colourless oil; all
spectroscopic and analytical properties were identical to those
reported above.
1-(1,3,6,2-Dioxazaborocan-2-yl)pentan-3-one
To a solution of boronate ester 8b (1.02 g, 4.81 mmol) in diethyl
ether (10 ml), diethanolamine (2.40 ml of a 2.0 M solution
in isopropanol, 4.80 mmol) was added dropwise. Refrigeration
of the resulting milky solution, yielded the title compound
1-(1,3,6,2-dioxazaborocan-2-yl)pentan-3-one (0.266 g, 1.34
mmol, 28%) as a white, hygroscopic, amorphous solid, after
filtration and drying under vacuum, over P2O5; δH (400 MHz;
CDCl3) 0.62–0.65 (2 H, m, CH2B), 1.03 (3 H, t, J 7.5, CH3), 2.46
(2 H, q, J 7.5, CH3CH2), 2.64–2.67 (2 H, m, CH2CH2B), 2.75–
2.81 (2 H, m, CH2N), 3.12–3.21 (2 H, m, CH2N), 3.81–3.86
(2 H, m, CH2O), 3.95–4.01 (2 H, m, CH2O), 6.39 (1 H, br s,
NH) (addition of D2O caused peak at δ 6.39 to disappear);
δC (100.6 MHz; CDCl3) 8.0 (CH3), 10.9 (br, CH2B), 36.0
(CH2CH2B), 38.6 (CH3CH2), 51.1 (CH2N), 63.2 (CH2O),
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-3-one 8g
The procedure outlined for the conversion of 11f to 8f was
followed on a 0.32 mmol scale using 1-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)hexan-3-one O-methyloxime 11d, to
afford the title compound 8g (0.047 g, 0.21 mmol, 65%) as a
colourless oil; νmax (film)/cmϪ1 3000–2880, 1710–1695, 1140,
1010; δH (300 MHz; CDCl3) 0.90 (3 H, t, J 7.3, CH3CH2), 0.89–
0.96 (2 H, m, CH2B), 1.23 [12 H, s, 2 × (CH3)2C], 1.58 (2 H,
sextet, J 7.3, CH3CH2), 2.37 (2 H, t, J 7.3, CH3CH2CH2), 2.56
(2 H, t, J 7.2, CH2CH2B); δC (75.5 MHz; CDCl3) 13.7 (CH3-
CH2), 17.5 (CH3CH2), 24.7 [(CH3)2C], 37.5 (CH2CH2B), 44.1
219.5 (C᎐O); δ (64.2 MHz; CDCl3) ϩ12.0; m/z (FAB) 200
᎐
B
(M ϩ H)ϩ [Found (HRMS): m/z 200.1465. C9H18BNO3
requires (M ϩ H)ϩ 200.1458].
(CH CH CH ), 83.0 [(CH ) C], 211.6 (C᎐O); δ (64.2 MHz;
᎐
3
2
2
3
2
B
CDCl3) ϩ33.9; m/z (CI, NH3) 227 (M ϩ H)ϩ, 244 (M ϩ NH4)ϩ
[Found (HRMS): m/z 227.1812. C12H23BO3 requires (M ϩ H)ϩ
227.1818].
1-[(4R,5R)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-
2-yl]pentan-3-one 26b
To a solution of diethanolamine derivative 1-(1,3,6,2-dioxaza-
borocan-2-yl)pentan-3-one (0.016 g, 0.080 mmol) and diol
(R,R)-19 (0.015 g, 0.058 mmol) in chloroform (1 ml), 10% HCl
(aq) (1 ml) was added. The biphasic solution was stirred at
room temperature for 1 hour then separated. The combined
organic layers were dried and evaporated to yield product 26b
(0.016 g, 0.045 mmol, 78%) as a colourless oil; [α]D27 Ϫ32.5 (c
0.75, CHCl3); δH (400 MHz; CDCl3) 0.95–1.09 (2 H, m, CH2B),
1.04 (3 H, t, J 7.5, CH3CH2), 1.56–1.82 (16 H, m, CH2
cyclopentyl), 2.41 (2 H, q, J 7.5, CH3CH2), 2.49–2.56 (2 H, m,
CH2CH2B), 3.23 (6 H, s, 2 × OCH3), 4.29 (2 H, s, 2 × CH);
δC (100.6 MHz; CDCl3) 8.0 (CH3CH2), 24.5, 24.6, 30.7,
31.3 (CH2 cyclopentyl), 35.4 (CH2CH2B), 36.7 (CH3CH2),
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyl-
pentan-3-one 8d
The procedure outlined for the conversion of 11f to 8f was
followed on a 4.39 mmol scale using 1-(4,4,5,5-tetrameth-
yl-1,3,2-dioxaborolan-2-yl)-4-methylpentan-3-one O-methyl-
oxime 11e, to yield the title compound 8d (0.33 g, 1.46 mmol,
33%) as a colourless oil, which was identical to that reported
above.
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyloctan-
3-one 8h
The procedure outlined for the conversion of 11f to 8f was
followed on a 1.14 mmol scale using 1-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)-4-methyloctan-3-one O-methyloxime
11g, to afford the title compound 8h (0.21 g, 0.78 mmol, 69%)
as a colourless oil; νmax (film)/cmϪ1 3000–2850, 1705, 1380,
1320, 1140; δH (300 MHz; CDCl3) 0.88 (3 H, t, J 7.0, CH3CH2),
0.89 (2 H, t, J 6.8, CH2B), 1.05 (3 H, d, J 6.9, CH3CH), 1.23
[12 H, s, 2 × (CH3)2C], 1.17–1.32 [6 H, m, CH3(CH2)3], 2.48–2.54
50.3 (OCH ), 80.8 (CHO), 87.9 (COCH ), 211.6 (C᎐O);
᎐
3
3
δB (62.4 MHz; CDCl3) ϩ35.2; m/z (FAB) 370 (M ϩ NH4)ϩ
[Found (HRMS): m/z 370.2766. C19H33BO5 requires (M ϩ
NH4)ϩ 370.2765].
1-(1,3,6,2-Dioxazaborocan-2-yl)-4-methylpentan-3-one
To a solution of boronate ester 8d (0.24 g, 1.06 mmol) in diethyl
ether (5 ml), diethanolamine (0.53 ml of a 2.0 M solution
in propan-2-ol, 1.06 mmol) was added dropwise. Refrigeration
of the resulting milky solution yielded the title compound
1-(1,3,6,2-dioxazaborocan-2-yl)-4-methylpentan-3-one (0.10 g,
0.47 mmol, 44%) as a white hygroscopic amorphous solid, after
filtration and drying under vacuum over P2O5; νmax (KBr)/cmϪ1
3050, 2980, 1690, 1420, 1265, 1070; δH (300 MHz; CDCl3) 0.62–
0.66 (2 H, m, CH2B), 1.07 [6 H, d, J 7.0, (CH3)2CH], 2.61–2.78
(1 H, m, CH CH), 2.57–2.62 (2 H, m, CH C᎐O); δ (75.5 MHz;
᎐
3
2
C
CDCl3) 5.1 (br, CH2B), 13.9 (CH3CH2), 16.6 (CH3CH), 22.7
(CH3CH2), 24.7 [(CH3)2C], 29.4 (CH3CH2CH2), 33.0 (CH2CH),
36.2 (CH C᎐O), 45.7 (CH CH), 83.0 [(CH ) C], 215.3 (C᎐O);
᎐
᎐
2
3
3 2
δB (64.2 MHz; CDCl3) ϩ33.6; m/z (FAB) 269 (M ϩ H)ϩ
[Found (HRMS): m/z 269.2290. C15H29BO3 requires (M ϩ H)ϩ
269.2288].
[5 H, m, CH C᎐O, CH N, (CH ) CH], 3.09–3.21 (2 H, m,
᎐
2
2
3 2
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)undecan-3-one
8e
CH2N), 3.80–3.86 (2 H, m, CH2O), 3.93–4.02 (2 H, m, CH2O),
6.41 (1 H, br s, NH) (addition of D2O causes peak at δ 6.41 to
disappear); δC (75.5 MHz; CDCl3) 10.7–11.8 (br, CH2B), 18.5
The procedure outlined for the conversion of 11f to 8f was
followed on a 1.14 mmol scale using 1-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)undecan-3-one O-methyloxime 11h, to
furnish the title compound 8e (0.30 g, 1.01 mmol, 89%) as a
colourless oil, which was identical to that reported above.
[(CH ) C], 37.0 (CH C᎐O), 40.9 [(CH ) C], 51.1 (CH N), 60.6
᎐
3
2
2
3
2
2
(CH O), 218.0 (C᎐O); δ (64.2 MHz; CDCl ) ϩ12.2; m/z (FAB)
᎐
2
B
3
214 (M ϩ H)ϩ [Found (HRMS): m/z 213.1541. C10H20BNO3
requires Mϩ 213.1536].
J. Chem. Soc., Perkin Trans. 1, 2000, 3250–3263
3261

View Article Online
1-[(4R,5R)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-
2-yl]-4-methylpentan-3-one 26d
1.26–1.53 [12 H, m, CH3(CH2)6], 2.42 [2 H, t, J 7.3, (CH2)6-
CH C᎐O], 2.63–2.67 (2 H, m, CH CH B), 2.75–2.80 (2 H, m,
CH2N), 3.12–3.20 (2 H, m, CH2N), 3.81–3.86 (2 H, m, CH2O),
3.91–4.01 (2 H, m, CH2O), 6.39 (1 H, br s, NH) (addition of
D2O caused peak at δ 6.39 to disappear); δC (100.6 MHz;
CDCl3) 14.1 (CH3CH2), 22.6, 24.2, 29.1, 29.2, 29.3, 31.8
᎐
2
2
2
To a solution of diethanolamine derivative 1-(1,3,6,2-dioxaza-
borocan-2-yl)-4-methylpentan-3-one (0.031 g, 0.145 mmol) and
diol (R,R)-19 (0.031 g, 0.12 mmol) in chloroform (1 ml), 10%
HCl (aq) (1 ml) was added. The biphasic solution was stirred at
room temperature for 1 hour then separated. The combined
organic layers were dried and evaporated to yield product 26d
(0.026 g, 0.071 mmol, 59%) after column chromatography
[1:10, ethyl acetate–petroleum ether (40–60 ЊC) as eluent]; [α]D27
Ϫ45 (c 1.0, CHCl3); δH (300 MHz; CDCl3) 0.96–1.03 (2 H, m,
CH2B), 1.08 [6 H, d, J 7.1, (CH3)2C], 1.59–1.78 (16 H, m, CH2
[CH (CH ) ], 39.2 (CH CH B), 43.1 [(CH ) CH C᎐O], 51.1
᎐
2
3
2
6
2
2
2
6
(CH N), 63.2 (CH O), 219.6 (C᎐O); δ (62.4 MHz; CDCl3)
᎐
2
2
B
ϩ12.1; m/z (FAB) 284 (M ϩ H)ϩ [Found (HRMS): m/z
284.2402. C15H30BNO3 requires (M ϩ H)ϩ 284.2397].
1-[(4R,5R)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-
2-yl]undecan-3-one 26e
cyclopentyl), 2.59 (2 H, t, J 7.2, CH C᎐O), 2.59 [1 H, septet,
᎐
2
J 7.0, (CH3)2CH], 3.22 (6 H, s, 2 × OCH3), 4.29 (2 H, s,
2 × CHO); m/z (CI, NH3) 384 (M ϩ NH4)ϩ [Found (HRMS):
m/z 384.2923. C20H35BO5 requires (M ϩ NH4)ϩ 384.2921].
To a solution of diethanolamine derivative 1-(1,3,6,2-dioxaza-
borocan-2-yl)undecan-3-one (0.025 g, 0.088 mmol) and diol
(R,R)-19 (0.023 g, 0.089 mmol) in chloroform (1 ml), 10% HCl
(aq) (1 ml) was added. The biphasic solution was stirred at
room temperature for 1 hour then separated. The combined
organic layers were dried and evaporated to yield product 26e
(0.029 g, 0.066 mmol, 76%) after column chromatography
[1:10, ethyl acetate–petroleum ether (40–60 ЊC) as eluent]; [α]D22
Ϫ21.5 (c 0.95, CHCl3); νmax (film)/cmϪ1 2980–2810, 1710, 1460–
1450, 1390–1360, 1240, 1140, 1075; 1H NMR was as reported;25
δC (75.5 MHz; CDCl3) 4.4 (br, CH2B), 14.1 (CH3CH2), 22.6,
24.2, 24.6, 24.8, 29.1, 29.3, 29.4, 31.3, 31.8 [CH3(CH2)6, CH2
1-(1,3,6,2-Dioxazaborocan-2-yl)-4,4-dimethylpentan-3-one
To a solution of boronate ester 8f (2.00 g, 8.33 mmol) in diethyl
ether (10 ml), diethanolamine (4.15 ml of a 2.0 M solution
in isopropanol, 8.30 mmol) was added dropwise. Refrigeration
of the resulting milky solution yielded the title compound 1-
(1,3,6,2-dioxazaborocan-2-yl)-4,4-dimethylpentan-3-one (0.80
g, 3.52 mmol, 43%) as a white amorphous solid, after filtration
and drying under vacuum over P2O5; mp 148 ЊC (Found: C,
58.1; H, 10.0; N, 6.1; B, 4.8. C11H22NO3 requires C, 58.2; H, 9.8;
N, 6.2; B, 4.8%); νmax (KBr)/cmϪ1 3050, 2980–2860, 1680, 1420,
1265, 1070; δH (300 MHz; CDCl3) 0.61–0.65 (2 H, m, CH2B),
cyclopentyl)], 37.2 (CH CH B), 42.3 [(CH ) CH C᎐O], 50.3
᎐
2
2
2
2
6
(OCH ), 80.8 (CHO), 87.9 (COCH ), 211.3 (C᎐O); δ (64.2
᎐
3
3
B
MHz; CDCl3) ϩ33.6; m/z (CI, NH3) 437 (M ϩ H)ϩ, 454 (M ϩ
NH4)ϩ [Found (HRMS): m/z 454.3708. C25H45BO5 requires
(M ϩ NH4)ϩ 454.3703].
1.13 [9 H, s, (CH ) C], 2.70–2.74 (2 H, m, CH C᎐O), 2.75–2.81
᎐
2
3
3
(2 H, m, CH2N), 3.09–3.20 (2 H, m, CH2N), 3.80–3.86 (2 H, m,
CH2O), 3.93–4.02 (2 H, m, CH2O), 6.42 (1 H, br s, NH) (addi-
tion of D2O caused peak at δ 6.42 to disappear); δC (75.5 MHz;
Monitoring of benzyl{3-[(4R,5R)-4,5-bis(1-methoxycyclo-
pentyl)-1,3,2-dioxaborolan-2-yl]-1-phenylpropylidene}amine 27
formation by 1H NMR
CDCl ) 26.8 [(CH ) C], 33.2 (CH C᎐O), 44.4 [(CH ) C], 51.1
᎐
3
3
3
2
3 3
(CH N), 63.2 (CH O), 216.4 (C᎐O); δ (128.3 MHz; CDCl3)
᎐
2
2
B
ϩ12.0; m/z (FAB) 228 (M ϩ H)ϩ [Found (HRMS): m/z
227.1692. C11H22BNO3 requires Mϩ 227.1693].
Method A. Activated granular molecular sieves (4 Å) were
added to a stirred solution of β-keto boronate ester 26g (0.10 g,
0.25 mmol) and benzylamine (0.055 ml, 0.50 mmol) in CDCl3
(4 ml). The solution was stirred under a nitrogen atmosphere
for 36 hours at room temperature. A sample was removed and
examined by 1H NMR, which showed the presence of title
compound 27 (1:8, starting material ketone 26g:product imine
27); δH (360 MHz; CDCl3) 3:5, mixture of diastereoisomers,
major diastereoisomer: 1.01 (2 H, t, J 7.3, CH2B), 1.54–1.76
1-[(4R,5R)-4,5-Bis(1-methoxycyclopentyl)-1,3,2-dioxaborolan-
2-yl]-4,4-dimethylpentan-3-one 26f
A solution of diethanolamine derivative 1-(1,3,6,2-dioxaza-
borocan-2-yl)-4,4-dimethylpentan-3-one (0.227 g, 1.00 mmol)
and diol (R,R)-19 (0.30 g, 1.16 mmol) in chloroform (30 ml)
and HCl (aq) (30 ml of a 0.04 M solution, 1.20 mmol) was
stirred at room temperature for 2 hours, then separated. The
organic phases were washed with water. Evaporation yielded a
colourless oil which was purified by flash chromatography
[1:10, ethyl acetate–petroleum ether (40–60 ЊC) as eluent]
affording the title compound 26f (0.34 g, 0.89 mmol, 89%); [α]D22
Ϫ46.5 (c 0.946, MeOH); νmax (film)/cmϪ1 2800–2828, 1707,
1392, 1366, 1240, 1076; δH (250 MHz; CDCl3) 0.92–0.98 (2 H,
m, CH2B), 1.12 [9 H, s, (CH3)3C], 1.58–1.78 (16 H, m, CH2
(16 H, m, CH cyclopentyl), 2.79–2.83 (2 H, m, CH C᎐N), 3.14
᎐
2
2
(6 H, s, 2 × OCH3), 4.21 (2 H, s, 2 × CHO), 4.67 (2 H, ABq,
J 14.9, separation 98.3, CH2Ph), 7.05–7.83 (10 H, m, H
aromatic); minor diastereoisomer: 1.04–1.09 (2 H, m, CH2B),
1.54–1.76 (16 H, m, CH2 cyclopentyl), 2.82–2.88 (2 H, m,
CH C᎐N), 3.24 (6 H, s, 2 × OCH ), 4.31 (2 H, s, 2 × CHO), 4.81
᎐
2
3
(2 H, s, CH2Ph), 7.05–7.83 (10 H, m, H aromatic).
Method B. β-Keto boronate ester 26g (0.13 g, 0.32 mmol) was
dissolved in benzylamine (8 ml). A Kugelrohr apparatus (50 ЊC,
2.0 mmHg) was used to distil excess benzylamine and water,
leaving an orange oil residue. A sample was removed from the
reaction and examined by 1H NMR, which showed the presence
of imine 27 (1:1, starting material ketone 26g:product imine
27): 1H NMR was as reported in Method A for imine 27.
cyclopentyl), 2.60–2.66 (2 H, m, CH C᎐O), 3.21 (6 H, s,
2 × OCH3), 4.28 (2 H, s, 2 × CHO); δC (62.9 MHz; CDCl3)
24.5, 24.6 (CH2 cyclopentyl), 26.7 [(CH3)3C], 30.8, 31.2 (CH2
᎐
2
cyclopentyl), 31.3 (CH C᎐O), 43.7 [(CH ) C], 50.3 (OCH ),
᎐
2
3
3
3
80.7 (CHO), 88.0 (COCH ), 215.9 (C᎐O); δ (128.3 MHz;
᎐
3
B
CDCl3) ϩ33.9; m/z (FAB) 381 (M ϩ H)ϩ [Found (HRMS): m/z
381.2800. C21H37BO5 requires (M ϩ H)ϩ 381.2812].
1-(1,3,6,2-Dioxazaborocan-2-yl)undecan-3-one
Acknowledgements
To a solution of boronate ester 8e (0.162 g, 0.55 mmol) in
diethyl ether (5 ml), diethanolamine (0.28 ml of a 2.0 M solu-
tion in propan-2-ol, 0.56 mmol) was added dropwise. Refriger-
ation of the resulting milky solution yielded the title compound
1-(1,3,6,2-dioxazaborocan-2-yl)undecan-3-one (0.048 g, 0.17
mmol, 31%) as a white hygroscopic amorphous solid, after fil-
tration and drying under vacuum over P2O5; δH (400 MHz;
CDCl3) 0.62–0.64 (2 H, m, CH2B), 0.88 (3 H, t, J 7.0, CH3CH2),
We thank the EPSRC for a studentship (award no. 96311892)
and Knoll Pharmaceuticals for a grant to H. E. S.
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