Efficient synthesis of B-iododialkyl- and B-alkyldiiodoboranes as their acetonitrile complexes: Application for the enolboration - Aldolization of ethyl ketones

Article abstract of DOI:10.1002/1522-2675(200210)85:10<3027::AID-HLCA3027>3.0.CO;2-H

A series of B-(iododialkyl)boranes and B-(alkyldiiodo)boranes have been readily synthesized as their MeCN complexes from the corresponding chloro- and bromoboranes by treatment with NaI or KI in MeCN. In the presence of EtN(i-Pr)₂, the B-(cyclo

Full text of DOI:10.1002/1522-2675(200210)85:10<3027::AID-HLCA3027>3.0.CO;2-H

Helvetica Chimica Acta Vol. 85 (2002)
3027
Efficient Synthesis of B-Iododialkyl- and B-Alkyldiiodoboranes as Their
Acetonitrile Complexes: Application for the Enolboration Aldolization of
Ethyl Ketones
by P.Veeraraghavan Ramachandran* , Mu-Fa Zou, and Herbert C.Brown*
Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, West Lafayette,
Indiana 47907-1393, USA
(phone: 765-494-5303; fax: 765-494-0239; e-mail: chandran@purdue.edu)
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday
A series of B-(iododialkyl)boranes and B-(alkyldiiodo)boranes have been readily synthesized as their
MeCN complexes from the corresponding chloro- and bromoboranes by treatment with NaI or KI in MeCN. In
the presence of EtN(i-Pr)2, the B-(cyclohexyldiiodo)borane-acetonitrile complex converts ethyl ketones
exclusively to the (Z)-enolates, which, upon aldolization with a series of aldehydes, provide the corresponding
syn-aldols exclusively in high yields.
1.Introduction. Of the several modified boranes available to the organic chemists,
the haloboranes have found significant applications in organic syntheses [1]. For
example, monochloroborane has been used for the preparation of dialkylchlorobo-
ranes, such as B-chloro(dicyclohexyl)borane and B-chloro(diisopinocampheyl)borane
(Aldrich: DIP-ChlorideTM). The former reagent is efficient for the anti-selective
enolborationÀaldolization reaction [2], and the latter is an excellent reagent for the
reduction of several classes of ketones in very high enantiomeric excess [3]. B-
Chloro(dialkyl)boranes also act as intermediates in the synthesis of the corresponding
alkylamines [4]. Dichloroborane has been used for the synthesis of the corresponding
B-alkyldichloroboranes, which give rise to syn-selective enolborationÀaldolization
reactions [5]. Dichloroborane-methyl sulfide has been utilized for the reduction of
alkyl or aryl azides to the corresponding amines [6]. Dibromoboranes have been used
in the synthesis of (E)- or (Z)-alkenes or (E,E)-, (E,Z)-, or (Z,Z)-dienes at well [7].
Recently, we have reported the cleavage of epoxides with the bromoborane-methyl
sulfide complex [8].
Although mono- and dichloro-, and mono- and dibromoboranes are commercially
available as their methyl-sulfide complexes, the corresponding iodoboranes are not
available. The synthesis of these iodoboranes involves the treatment of borane-methyl
sulfide with I2 in CS2 [9]. The hydroboration of alkenes with iodoboranes is not always
clean, though [10]. As an alternative, we treated dialkylboranes with I2 [10], or applied
the Matteson procedure [11], i.e., the in situ hydroboration with triiodoborane and tri-
methylsilane, for the preparation of B-dialkyliodoboranes [12]. However, these proce-
dures also failed to provide the corresponding B-alkyldiiodoboranes efficiently.
In contrast to B-alkylchloro- and B-alkylbromoboranes, the corresponding
iodoboranes have been sparingly used in organic synthesis. This could be attributed

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Helvetica Chimica Acta Vol. 85 (2002)
to the difficulties in their preparation and their lack of stability. We had shown that B-
iododiisopinocampheylborane is an excellent reagent for the asymmetric ring-opening
of meso-epoxides [13] and that B-dicyclohexyliodoborane is a syn-selective enolbora-
tion-aldolization reagent [14].
We have now found that both B-dialkyliodo- and B-alkyldiiodoboranes can be
readily synthesized via a quantitative halogen-exchange reaction. Our successful
synthesis of these iodoboranes and their application to the enolboration aldolization
reactions of ethyl ketones are reported herein.
2.Results and Discussion.
Preparation of B-Dialkyliodoborane-Acetonitrile
Complex. Upon dissolving B-chlorodicyclohexylborane in MeCN, the 11B-NMR
spectrum revealed a shift from d 74to 8 ppm, indicating strong complex formation.
Addition of 1.2 equiv. of NaI or KI dissolved in MeCN afforded a solid, presumably
NaCl or KCl, respectively, and the 11B-NMR spectra revealed a singlet at d 5 ppm
(Scheme 1). Although a downfield shift was expected in the NMR spectrum for the
iodoborane compared to the chloroborane complex, the observed upfield shift may be
attributed to a stronger MeCN complex with a superior Lewis acid.
Scheme 1
Filtration of the inorganic salt and removal of MeCN provided a solid compound
well-soluble in pentane, CH2Cl2, and CCl4. However, upon dissolving in Et2O or THF,
the solution became warm, and the 11B-NMR spectrum showed a peak at d 52 ppm,
indicating that, as expected, the iodoborane reagent had cleaved the ether (Scheme 2).
Thus, we have discovered a trans-halogenation procedure for the synthesis of alkyl-
iodoboranes. We applied this procedure to the synthesis of a series of B-alkyliodobo-
ranes as their MeCN complexes from the corresponding chloro- and bromoboranes
(Scheme 1).
Preparation of B-Alkyldiiodoboranes. Although it should be possible to prepare B-
alkyldiiodoboranes via i) the hydroboration of an alkene with diiodoborane-methyl
sulfide [9], ii) the addition of I2 to the corresponding alkylborane (RBH2), or iii)
Matteson×s trimethylsilane reduction of the corresponding dichloroborane, we expe-
rienced difficulties in obtaining pure B-alkyldiiodoboranes with all of the above
procedures. We, therefore, applied the new trans-halogenation procedure for the

Helvetica Chimica Acta Vol. 85 (2002)
3029
Scheme 2
synthesis of B-alkyldiiodoboranes. The 11B-NMR spectrum of B-dichlorocyclohexyl-
borane in MeCN revealed a signal at d 6 ppm as compared to 62 ppm in pentane or
CH2Cl2. Treatment of this complex with 2.5 equiv. of NaI or KI in MeCN also led to the
precipitation of a solid, presumably NaCl or KCl, respectively. Surprisingly, unlike in
the case of the B-dialkyliodoborane-acetonitrile complex, the 11B-NMR spectrum
exhibited no change (Scheme 3). However, THF was instantaneously cleaved
(11B-NMR: d 31 ppm), revealing that the conversion to the diiodoborane-acetonitrile
complex had occurred.
Scheme 3
Removal of the solvent (MeCN) provided a solid mixture of ChxBI2 ¥ MeCN, NaCl,
and NaI. Chemically pure ChxBI2 ¥ MeCN was obtained by selective dissolution in
CH2Cl2, followed by filtration and removal of the solvent. The solubility of ChxBI2 ¥
MeCN was examined next. Unlike Chx2BI ¥ MeCN, ChxBI2 ¥ MeCN does not dissolve in
hexanes. However, it readily dissolves in MeCN and CH2Cl2. The 11B-NMR spectra of
ChxBI2 ¥ MeCN in these solvents revealed peaks at d 6 and 8 ppm, respectively. A series
of B-alkyldiiodoboranes were prepared from the corresponding B-alkyldichloro- and
B-alkyldibromoboranes (Scheme 3).
With the above mono- and dialkyliodoborane-acetonitrile complexes in our
hands, we decided to examine their utility in organic synthesis. We reported earlier
that B-dicyclohexyliodoborane is an efficient (Z)-enol- and syn-aldol-produc-
ing reagent [14]. Although we have already reported the utility of B-alkyldi-
chloro- and B-alkyldibromoboranes [5], we could not test the corresponding
diiodoboranes since none of our earlier procedures afforded the pure reagent.

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Helvetica Chimica Acta Vol. 85 (2002)
Hence, we decided to examine ChxBI2 ¥ MeCN for the enolborationÀaldolization
reaction.
EnolborationÀAldolization with ChxBI2 ¥ MeCN Complex. Addition of EtN(i-Pr)2
(1 equiv.) to the brown solution of ChxBI2 ¥ MeCN in CH2Cl2, followed by 11B-NMR-
spectroscopic analysis, revealed a singlet at d 12 ppm, indicating that the amine
probably displaces MeCN from the complex. We used the amine complex for the
enolboration of diethyl ketone in CH2Cl2 at À788. The mixture was stirred for 1 h,
followed by addition of PhCHO at À788. After 2 h, the mixture was quenched with
phosphate buffer (pH 7.0) and oxidized (H2O2). 1H-NMR Analysis of the crude
product revealed the exclusive formation of the syn-aldol, thus providing the evidence
that the enolization was ꢀ99% stereoselective (Scheme 4). Distillation provided an
87% yield of the pure product.
Scheme 4
The general character of the syn-selective aldol reaction with B-cyclohexyldiiodo-
borane reagent was further examined with a branched-chain ketone, i.e., 2-methyl-
pentan-3-one, and an aralkyl ketone, i.e., propiophenone, which were reacted with
PhCHO, propionaldehyde, and isobutyraldehyde. Exclusive formation of syn-aldols
was observed in all these cases. In the case of 2-methylpentan-3-one, the enol borinate
was formed solely on the ethyl side (ꢀ 99% regioselectivity).
When the enolization of 1-phenylbutan-2-one was carried out under the standard
conditions, no regioselectivity was observed. Enolboration occurred at both sides of the
CˆO group (Scheme 5). Nevertheless, the resulting a-substituted b-hydroxyketones
were found to be exclusively syn-configured.
In summary, we have described a facile method for the preparation of B-
dialkyliodoboranes and B-alkyldiiodoboranes as their MeCN complexes via a halogen-
exchange reaction. B-Cyclohexyldiiodoborane is a versatile reagent for the syn-
selective enolboration of a series of ethyl ketones.
We thank Dr. M. Venkat Ram Reddy for some preliminary experiments and the Herbert C. Brown Center
for Borane Research for financial support of this work.

Helvetica Chimica Acta Vol. 85 (2002)
3031
Scheme 5
Experimental Part
General. All haloboranes were prepared according to [5]. CH2Cl2 and MeCN were distilled over CaH2 and
stored over 4-ä molecular sieves. EtN(i-Pr)2 was distilled over CaH2 and directly used. NaI was dried in vacuo at
1508 for 3 h. All glassware was oven-dried, cooled, and assembled under N2. All of the experiments were carried
out in a 100-ml round-bottom flask capped with a rubber septum, a magnetic stirring bar, and a connecting tube
attached to a Hg bubbler under N2. The experimental techniques used in handling air- and moisture-sensitive
compounds have been described in [15]. The 1H-, 11B- and 13C-NMR spectra were recorded on a Varian Gemini-
300 spectrometer with a Nalorac-Quad probe.
General Procedure for the Halogen-Exchange Reaction. Preparation ofChxBI 2 ¥ MeCN Complex. MeCN
(5 ml) was added to ChxBCl2 (990 mg, 6 mmol) at 08. ChxBCl2 ¥ MeCN was formed immediately as a white solid
that dissolved in MeCN gradually. The 11B-NMR spectrum showed a peak at d 6 ppm. To this soln. was added
15 ml of a 1m soln. (2.5 equiv.) of NaI in MeCN at r.t., and the mixture was stirred at this temp. for 3 h when NaCl
was separated. The 11B-NMR spectrum showed a peak at d 6 ppm. The solvent was pumped off when a solid
mixture was obtained. ChxBI2 ¥ MeCN was dissolved in CH2Cl2, and NaCl and NaI were removed by filtration.
The salts were washed with CH2Cl2 (3 Â 2 ml). The 11B-NMR spectrum showed a peak at d 8 ppm. Removal of
CH2Cl2 gave ChxBI2 ¥ MeCN as a solid.
Data ofChxBI 2 ¥ MeCN: 11B-NMR (CH2Cl2): 8. 1H-NMR (CDCl3): 2.49 (s, 3 H); 1.88 0.80 (m, 11 H).
13C-NMR (CDCl3): 117.0; 28.5; 27.4; 26.8; 3.1. (It is usually difficult to observe the C-atom a to the B-atom in a
13C-NMR spectrum due to rapid quadrapole-induced relaxation.)
General Procedure for the Enolboration and Aldolization. The above soln. of ChxBI2 ¥ MeCN in CH2Cl2 was
cooled to À788, and the ketone (5 mmol) was added slowly. To this mixture, EtN(i-Pr)2 (774mg, 6 mmol) was
added dropwise. The mixture was kept at À788 for 1 h. The 11B-NMR spectrum of this mixture showed a peak at
d 41 ppm, revealing the completion of the reaction. The aldehyde (5 mmol) was then added dropwise at À788,
and the mixture was stirred for 3 h. The 11B-NMR spectrum showed a peak at d 31 ppm, indicating the formation
of the boron aldolate. The mixture was then added to a phosphate buffer (pH 7) at r.t. and extracted with
CH2Cl2 (3 Â 20 ml). The combined org. soln. was concentrated. The residue was dissolved in Et2O (20 ml), and
MeOH (5 ml) was added. The soln. was cooled to 08, aq. 30% H2O2 (3 ml) was added slowly, and the oxidation
was continued for 3 h. The product was extracted with Et2O (3 Â 20 ml). The combined org. layer was washed
with aq. NaHCO3 (3 Â 10 ml) and brine (3 Â 10 ml), dried (MgSO4), and concentrated. The regio- and
diastereoselectivities were determined from the 1H-NMR spectrum of the crude product and further proved by
1H-NMR spectrum of the pure products obtained after a flash chromatography (SiO2 ; hexanes/AcOEt 8 :1).
syn-1-Hydroxy-2-methyl-1-phenylpentan-3-one. 1H-NMR (CDCl3): 7.40 7.20 (m, 5 H); 5.04( d, J ˆ 4.05,
1 H); 3.20 3.10 (OH); 2.84( dq, J ˆ 4.05, 7.14, 1 H); 2.58 2.26 (m, 2 H); 1.08 (d, J ˆ 7.14, 3 H); 1.00 (t, J ˆ 7.23,
3 H). 13C-NMR (CDCl3): 141.9; 128.3; 127.4; 126.0; 73.3; 52.3; 35.5; 10.6; 7.5.
syn-5-Hydroxy-4,6-dimethylheptan-3-one. 1H-NMR (CDCl3): 3.52 (dd, J ˆ 2.97, 8.46, 1 H); 2.88 2.80
(OH); 2.74( dq, J ˆ 2.97, 7.23, 1 H); 2.65 2.42 (m, 2 H); 1.73 1.56 (m, 1 H); 1.12 (d, J ˆ 7.23, 3 H); 1.06 (t, J ˆ

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Helvetica Chimica Acta Vol. 85 (2002)
7.26, 3 H); 1.01 (d, J ˆ 6.51, 3 H); 0.86 (d, J ˆ 6.84, 3 H). 13C-NMR (CDCl3): 76.3; 47.2; 34.9; 30.6; 19.07; 19.01;
9.6, 7.7.
syn-5-Hydroxy-4-methylheptan-3-one. 1H-NMR (CDCl3): 3.82 (m, 1 H); 2.75 (OH); 2.70 2.40 (m, 3 H);
1.61 1.30 (m, 2 H); 1.13 (d, J ˆ 7.23, 3 H); 1.06 (t, J ˆ 7.23, 3 H); 0.96 (t, J ˆ 7.26, 3 H). 13C-NMR (CDCl3): 72.6;
49.3; 35.1; 26.9; 14.3; 10.5; 9.9; 7.6.
syn-1-Hydroxy-2,4-dimethyl-1-phenylpentan-3-one. 1H-NMR (CDCl3): 7.40 7.20 ( m, 5 H); 5.00 (d, J ˆ
3.84, 1 H); 3.15 (OH); 2.99 (m, 1 H); 2.60 (m, 1 H); 1.11 1.05 (m, 6 H); 0.99 (d, J ˆ 6.90, 3 H). 13C-NMR
(CDCl3): 141.9; 128.3; 127.5; 126.1; 73.6; 50.8; 40.7; 18.1; 17.8; 11.1.
syn-3-Hydroxy-2-methyl-1,3-diphenylpropan-1-one. 1H-NMR (CDCl3): 8.00 7.90 (m, 2 H); 7.62 7.21
(m, 8 H); 5.25 (d, J ˆ 2.34, 1 H); 3.75 3.60 (m, 2 H); 1.20 (d, J ˆ 7.26, 3 H). 13C-NMR: 205.8; 141.9; 135.7;
133.6; 128.8; 128.7; 128.5; 128.3; 127.4; 126.1; 73.1; 47.1; 11.2.
syn-4-Hydroxy-3-methyl-1,4-diphenylbutan-2-one. 1H-NMR (CDCl3): 7.40 7.20 (m, 8 H); 7.10 (m, 2 H);
4.97 (d, J ˆ 3.84, 1 H); 3.64 (s, 2 H); 3.02 2.90 (m, 2 H); 1.09 (d, J ˆ 7.14, 3 H). 13C-NMR (CDCl3): 212.8; 141.7;
‡
133.5; 129.5; 128.8; 128.4; 127.5; 127.2; 126.0; 73.5; 51.7; 49.6; 10.9. EI-MS: 255 ([ M ‡ 1] ), 237, 149, 119, 107, 91,
57. Anal. calc. for C17H18O2: C 80.31, H 7.09; found: C 80.17, H 7.17.
syn-1-Hydroxy-1,2-diphenylpentan-3-one. 1H-NMR (CDCl3): 7.40 7.16 (m, 10 H); 5.35 (d, J ˆ 6.51, 1 H);
3.97 (d, J ˆ 6.51, 1 H); 2.84(OH); 2.44 2.28 ( m, 1 H); 2.25 2.06 (m, 1 H); 0.86 (t, J ˆ 7.23, 3 H). 13C-NMR
(CDCl3): 211.5; 141.4; 134.3; 129.6; 128.7; 128.2; 128.1; 128.0; 127.9; 127.7; 126.6; 74.5; 65.8; 36.4; 7.6. EI-MS: 255
‡
([M ‡ 1] ), 237, 205, 149, 107, 91, 57. Anal. calc. for C17H18O2: C 80.31, H 7.09; found: C 80.22, H 7.01.
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Received June 11, 2002