Factors affecting reactions of trialkylcyanoborates with imidoyl chlorides/trifluoroacetic anhydride

Article abstract of DOI:10.1016/j.tet.2015.06.038

Abstract Methods for generating tert-alkyl organoboron species are in high demand as they are invaluable intermediates for the synthesis of quaternary carbon centres. Herein we report investigations into generation of tert-alkyl organoboron species using imidoyl chlorides as reagents in the organoboron cyanidation reaction. Although alkenyl side-products predominate in particularly hindered cases, tert-alkyl organoboron species can be successfully generated for less hindered examples.

Full text of DOI:10.1016/j.tet.2015.06.038

Tetrahedron 71 (2015) 6285e6289
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Factors affecting reactions of trialkylcyanoborates with imidoyl
chlorides/trifluoroacetic anhydride
,
a
,
b
Dyfyr Heulyn Jones a, Keith Smith a , Mark C. Elliott , Gamal A. El-Hiti
*
*
a School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK
b Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, PO Box 10219, Riyadh 11433,
Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 April 2015
Received in revised form 2 June 2015
Accepted 9 June 2015
Available online 15 June 2015
Methods for generating tert-alkyl organoboron species are in high demand as they are invaluable in-
termediates for the synthesis of quaternary carbon centres. Herein we report investigations into gen-
eration of tert-alkyl organoboron species using imidoyl chlorides as reagents in the organoboron
cyanidation reaction. Although alkenyl side-products predominate in particularly hindered cases, tert-
alkyl organoboron species can be successfully generated for less hindered examples.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Cyanoborate
Rearrangement
Hydroboration
Imidoyl chloride
1. Introduction
is possible to envisage introducing chirality into the imidoyl chlo-
ride, it was of interest to us to investigate whether a third migration
The formation of CeC bonds using boron-to-carbon alkyl group
migrations is an invaluable transformation in organic chemistry.1
Such reactions can involve one, two or three migrations, depend-
ing on the number of available leaving groups. There has been
considerable interest of late in such migration reactions that give
rise to tert-alkyl organoboron species, as there are protocols avail-
able to use these in the generation of otherwise difficult to syn-
thesise quaternary carbon centres.2e8
could be induced in the cyanidation reaction when using an imidoyl
chloride as the acylating reagent.
Several organoboron reactions have been developed that utilize
all three alkyl groups of a trialkylborane, giving a tert-alcohol as the
final product following oxidation of the tert-alkyl organoboron
intermediate.9e12 Of these reactions, the cyanidation reaction is
particularly useful as it proceeds under mild conditions, is tolerant
of sensitive functional groups and the doubly-migrated ketone
product is also accessible using the appropriate reaction
conditions.11,13e15
Although trifluoroacetic anhydride (TFAA) or benzoyl chloride is
usually the acylating reagent used in the cyanidation reaction, it has
been shown that N-phenylbenzimidoyl chloride (1) successfully
induces two boronecarbon migrations to give the intermediate 2,
which on oxidation gives the ketone product (Scheme 1).15 Since it
Scheme 1. Imidoyl chloride-induced cyanidation reaction.
It was reasoned that by adding excess trifluoroacetic anhydride
(TFAA) to the intermediate of type 2 (Scheme 1), acylation would
occur on nitrogen, thereby promoting the migration of the third
and final alkyl group, as occurs in the direct reaction of tri-
alkylcyanoborates with excess TFAA.13 Our results indicate that
such a process is indeed possible in cases when the trialkylborane is
not extremely hindered.
* Corresponding authors. Tel.: þ44 (0)29 20870600 (K.S.); tel.: þ44 (0)29
20874686 (M.C.E.); e-mail addresses: smithk13@cardiff.ac.uk (K. Smith), elliottmc@
cardiff.ac.uk (M.C. Elliott).
http://dx.doi.org/10.1016/j.tet.2015.06.038
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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D.H. Jones et al. / Tetrahedron 71 (2015) 6285e6289
2. Results/discussion
present in the TFAA. Such alkenyl species have been reported as
minor side products in the traditional cyanidation reaction when
using particularly hindered trialkylboranes,11 and also in the DCME
reactions of certain borinic esters16, which, upon heating, give the
alkenyl products almost quantitatively.17
The mixed trialkylborane 3 was chosen as the first substrate to
be studied, as a chiral tert-alcohol product would allow evaluation
of any future cyanidation reactions utilizing chiral imidoyl chlo-
rides. An authentic sample of racemic tert-alcohol 4 was prepared
by the sequential hydroboration of 2,3-dimethyl-2-butene, cyclo-
pentene and 4-methoxystyrene to give 3, which was subsequently
taken through the dichloromethyl methyl ether (DCME) protocol to
give 4 (Scheme 2).12
Many factors (both steric and electronic in nature) affect boron-
to-carbon migrations,1 and so imidoyl chlorides 7e9 were chosen
to probe whether the electronic and/or steric characteristics of the
imidoyl chloride could influence the reaction in such a way as to
promote the third alkyl group migration to give, after oxidation,
tertiary alcohol 4. Imidoyl chlorides 7 and 8 (Fig. 1) were chosen to
test whether an electron-withdrawing substituent could promote
the third migration, while imidoyl chloride 9 was chosen to probe
whether the third migration could be promoted by the alleviation
of steric hindrance around boron.1
Scheme 2. Formation of a chiral tertiary alcohol by the DCME reaction.
Fig. 1. Imidoyl chlorides chosen for study.
Mixed organoborane 3 was converted into its cyanoborate by
stirring under nitrogen with powdered potassium cyanide for 1 h.
This was then stirred overnight at room temperature with N-phe-
nylbenzimidoyl chloride (1), before excess TFAA was added and the
reaction mixture heated to 40 ꢀC for 14 h 1H NMR analysis following
oxidation and work-up showed the presence of ketone 5 and novel
alkene 6 (Scheme 3) in a 62:38 ratio, respectively, with no presence
of tert-alcohol 4. After chromatographic separation, compound 5
was isolated in 40% yield and compound 6 in 31% yield.
Imidoyl chlorides 7e9 were added to the potassium cyanoborate
salt of 3 and, following stirring at room temperature overnight, an al-
iquot was taken, oxidised and worked-up. Ketone 5 was clearly visible
as the major product by 1H NMR analysis of the products when using
imidoyl chlorides 7 and 9, indicating that the first two migrations had
been successful. When using imidoyl chloride 8, however, only the
alcohols arising from the oxidation of 3 could be seen in the 1H NMR
spectrum of the product. An aliquot taken after heating the reaction
mixture of 8 overnight at 80 ꢀC contained only trace amounts of 5,
while further heating resulted in darkening of the solution and for-
mation of a black polymeric material. Imidoyl chlorides possessing
electronewithdrawing substituents are known to be less prone to at-
tack by nucleophiles,18 which could explain the apparent lack of re-
activity of imidoyl chloride 8 with the potassium cyanoborate salt of 3.
Excess TFAA was added to the reaction mixtures involving 7 and
9, and the reaction mixtures were heated to 40 ꢀC overnight (Table
1). 1H NMR analysis following work-up for both reactions showed
an identical ratio of 5 and 6, with no sign of tert-alcohol 4 (Table 1).
The presence of the bulky isopropyl groups of 9 seemed to have had
minimal effect on the course of the reaction, whilst the addition of
a nitro group into the 4-position of the aryl ring of 7 increased the
production of alkene 6.
imidoyl chloride
Given that alkene side-products of type 6 are seen in traditional
cyanidation reactions (using TFAA alone as the acylating reagent)
only when particularly bulky trialkylboranes are used,11 it was
reasoned that boranes lacking the bulky thexyl (2,3-dimethyl-2-
butyl) group of intermediate 10 might allow the third migration
to give a tert-alcohol product. Attempts were therefore made to
displace the thexyl group from 10.
Scheme 3. Reaction of imidoyl chloride 1 with mixed trialkylborane 3.
Using 7, intermediate 10 was heated to 100 ꢀC with excess 1-
octene in an attempt to replace the thexyl group with an n-octyl
group via a displacement reaction (Entry 5, Table 1).19 1H NMR
analysis following subsequent reaction with TFAA and oxidation
showed the presence of 5 (ca. 61% yield) and 1-octene (ca. 79%
Ketone 5 is almost certainly the product from the oxidation of
the intermediate of type 2 following two migrations, whilst alkene
6 may be the product of protodeboronation of intermediate 2, along
with elimination of amine, facilitated by small amounts of acid

D.H. Jones et al. / Tetrahedron 71 (2015) 6285e6289
6287
Table 1
To our delight, the reaction of tri-n-octylborane (which would
have contained around 17% of the 2-octylbis(1-octyl)borane isomer,
as the hydroboration of 1-octene with BH3 is not entirely regiose-
lective)21 with 7, followed by reaction with TFAA and oxidation, gave
a mixture of ketone and tert-alcohol (Entry 1, Table 2), strongly
suggesting that the production of 6 was indeed due to the steric bulk
of 3. In fact, the tert-alcohol products arising from three migrations
were even accessible with moderately hindered trialkylboranes such
as tricyclopentylborane (Entry 2, Table 2) and di-n-octylthexylborane
(Entry 3, Table 2), along with various amounts of the ketone and
alkene products. The latter result shows that migration of a thexyl
group is possible for this reaction, and by comparison with the lack of
migration of the group in the case of 3 suggests that increasing bulk
at the migration terminus is responsible for diversion of the reaction
pathway to give alkene products. The migration of the thexyl group
was entirely during the final rearrangement step, so that no thexyl-
containing ketone was found. This is consistent with previous results
for cyanidation reactions,15 but in contrast with the situation for
some other reactions, such as our recently reported reactions with
halomethyllithium reagents.6,22
Initial investigative reactions using trialkylborane 3
imidoyl
chloride
Entry
Imidoyl chloride
Product proportionsa
3. Conclusion
5 (%)
6 (%)
1
2
3
4
5
6
1
7
8
9
62 (40)b
22
0
22
100
100
38 (31)b
In conclusion, promoting a third boronecarbon migration in
organoboron intermediates obtained from reactions of imidoyl
chlorides with trialkylcyanoborates is possible for trialkylboranes
that are relatively unhindered. Several imidoyl chlorides of differ-
ent electronic character and steric hindrance were tested in re-
actions with trialkylborane 3; all except one of the imidoyl
chlorides reacted to give a double-migrated intermediate, which on
further reaction with TFAA gave alkene 6, most likely due to steric
compression in the necessary transition state for a third migration
due to a combination of hindrance at the migration terminus and
a bulky migrating group. For less hindered trialkylboranes, the in-
termediates from reactions with imidoyl chloride 7 react with TFAA
and following oxidation give the tert-alcohol products from a third
boronecarbon migration. This opens up the exciting possibility of
developing an enantioselective synthesis of moderately un-
hindered tert-alcohols through the use of chiral imidoyl chlorides in
the cyanidation reactions of unsymmetrical trialkylboranes. Fur-
ther work is now needed in order to identify suitable
trialkylborane-reagent combinations.
78
Trace
78
0
7 (excess 1-octene)
7 (acetaldehyde)
0
a
Based on relative integrations by 1H NMR spectroscopy.
Isolated yields in parentheses.
b
recovered) but no n-octanol, indicating that the reaction pathway
to give 6 had been suppressed completely, although incorporation
of the n-octyl group had been unsuccessful.
A similar approach of replacing the thexyl group with an n-butyl
group was attempted by first displacement with acetaldehyde,20
followed by addition of n-BuLi to displace the ethoxy group gen-
erated (Entry 6, Table 1). This again resulted in the complete sup-
pression of the reaction pathway to give 6, but none of the tert-
alcohol from migration of the n-butyl group was observed by 1H
NMR spectroscopy. The only product identified was 5, the yield of
which was in the order of 70%.
A possible explanation for these results is that the methods were
successful in displacing 2,3-dimethyl-2-butene (thexene) but not in
the subsequent incorporation of an alkyl group.
4. Experimental section
To ascertain whether the steric bulk of 3/10 was responsible for
the formation of 6, a brief study was carried out of substrate scope
for the reaction using imidoyl chloride 7, using trialkylboranes of
different steric hindrance (Table 2).
4.1. General experimental details
Melting point determinations were performed by the open
capillary method and are reported uncorrected. 1H and 13C NMR
Table 2
Substrate scope using imidoyl chloride 7
Entry
Substituents R
R1
Yield (%)
R2
R3
H
R4
12
13
14
1
2
3
4
n-C8H17
c-Pent
n-C8H17
4-MeOC6H4(CH2)2
n-C7H15
e(CH2)4e
n-C7H15
n-C8H17
c-Pent
Thexyl
Thexyl
49a (12a)
39 (12b)
15 (12c)
0
17 (13a)
29 (13b)
18 (13a/c)
5 (5)
0
1b
H
10c (14c)
55 (6)
e(CH2)4e
a
Based on isolated yields following purification.
a 93:7 mixture of 14 and an isomeric alkene.
88:12 E/Z ratio.
b
c

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D.H. Jones et al. / Tetrahedron 71 (2015) 6285e6289
chemical shifts (
d
) are reported in parts per million (ppm) relative
was fitted to the remaining neck of the flask. The flask was flushed
with N2 for 10 min, and cooled to 0 ꢀC. Mixed trialkylborane 3
(5.0 mmol) was prepared as described above. The side arm was
rotated to introduce the cyanide, and the mixture left to stir for an
additional hour, whereupon the cyanide dissolved. N-Phenyl-
benzimidoyl chloride (1) (1.295 g, 5.5 mmol, in 6 mL of dry diglyme)
was added drop-wise to the solution of 3, and the reaction mixture
left to stir overnight at rt. Trifluoroacetic anhydride (7 mL,
50.0 mmol, excess) was added drop-wise, and the mixture heated
to 40 ꢀC for 14 h. Excess trifluoroacetic anhydride was evaporated
under reduced pressure via the stopcock, and the mixture cooled to
0 ꢀC. The mixture was oxidised as in the synthesis of 4, and 1H NMR
analysis following oxidation and work-up showed the presence of 5
and 6 in a 62:38 ratio, respectively. The compounds were separated
by column chromatography (silica, n-hexane then an increasingly
more polar hexaneꢁdiethyl ether mixture) to give 5 (0.46 g, 40%),
as a viscous yellow oil;25 Rf¼0.30 (n-hexane); vmax (neat/cmꢁ1):
1708 (C]O), 1612 (C]C); dH (400 MHz; CDCl3): 7.10 (2H, d,
J¼8.6 Hz, CH), 6.83 (2H, d, J¼8.6 Hz, CH), 3.77 (3H, s, CH3),
2.88e2.79 (3H, m, CH2, CH), 2.77e2.70 (2H, m, CH2), 1.83e1.47 (8H,
m, CH2); dC (125 MHz; CDCl3): 212.4 (quat C), 158.0 (quat C), 133.5
(quat C), 129.3 (CH), 113.9 (CH), 55.3 (CH3), 51.6 (CH), 43.6 (CH2),
29.0 (CH2), 28.8 (CH2), 26.0 (CH2); LRMS; EIþ m/z (%): 232 (Mþ,
36%), 163 (54), 121 (100); and 6 (0.33 g, 31%), as a colourless oil;
Rf¼0.45 (n-hexane); vmax (neat/cmꢁ1): 3031 (alkene CH), 1612 (C]
C); dH (400 MHz; CDCl3): 7.11 (2H, d, J¼8.6 Hz, CH), 6.83 (2H, d,
J¼8.6 Hz, CH), 5.43e5.16 (1H, m, CH), 3.79 (3H, s, CH3), 2.56 (2H, t,
J¼7.3 Hz, CH2), 2.32e2.16 (4H, m, CH2), 2.11 (2H, t, J¼6.8 Hz, CH2),
1.67e1.52 (4H, m, CH2); dC (125 MHz; CDCl3): 157.7 (quat C), 143.8
(quat C), 134.7 (quat C), 129.3 (CH), 119.2 (CH), 113.7 (CH), 55.2
(CH3), 35.1 (CH2), 33.6 (CH2), 31.8 (CH2), 28.6 (CH2), 26.4 (CH2), 26.3
(CH2); HRMS; EIꢁMS m/z: calcd for C15H20O 216.1514, found
216.1513 (Mþ, 60%).
to TMS, and coupling constants J are reported to the nearest 0.1 Hz.
C, CH, CH2, or CH3 13C signals are assigned from DEPT-90 and 135
spectra. Low and high-resolution mass spectra were recorded on
a time-of-fight mass spectrometer using electron impact (EI). High-
resolution mass spectra were recorded only for novel compounds.
IR spectra were recorded on a FTꢁIR spectrometer as a thin film
(liquid samples) or applied as a solution in chloroform, and the
chloroform was allowed to evaporate (solid samples). Column
chromatography was carried out using either 60A (35e70 mm) silica
or neutral alumina, and thin layer chromatography was conducted
on aluminium-backed silica plates. Imidoyl chlorides 1, and 7e9
were prepared using literature procedures.15,18,23,24
4.2. Synthesis of an authentic sample of 4
An oven-dried 100 mL round bottomed flask equipped with
a magnetic stirrer bar and septum was flushed with N2 for 10 min.
Borane-THF complex solution (1.0 M, 5.0 mL, 5.0 mmol) was added
drop-wise and the flask was cooled to ꢁ10 ꢀC using an ice-salt bath.
2,3-Dimethyl-2-butene (0.63 g, 7.5 mmol) was added drop-wise
with stirring, and the solution left to stir for a further 90 min be-
fore being cooled to between ꢁ30 and ꢁ20 ꢀC (dry ice-acetonitrile).
Cyclopentene (0.44 mL, 5.0 mmol) was added slowly with stirring,
and the reaction mixture was left to stir for 90 min. 4-
Methoxystyrene (0.67 mL, 5.0 mmol) was added drop-wise and
the solution left to warm to room temperature (rt) and stirred for
an additional 1 h. Dichloromethyl methyl ether (0.50 mL, 5.5 mmol)
was added drop-wise at 0 ꢀC, and a freshly prepared solution of
lithium 3-ethylpentan-3-olate in THF (prepared by the drop-wise
addition of n-BuLi to a solution of 3-ethyl-3-pentanol) introduced
drop-wise via a cannula with stirring over a 20 min period. Once
the addition was complete, the ice bath was removed and the
mixture left to stir for a further 1 h. Anhydrous ethylene glycol
(0.90 mL, 16.0 mmol) was added and the solution was left to stir for
1 h at rt. The flask was then placed in an ice bath, and a solution of
sodium hydroxide (1.20 g in 5 mL of distilled water) added carefully
drop-wise. Once the initial reaction subsided, a solution of hydro-
gen peroxide in water (30% by weight, 4.0 mL) and ethanol (5 mL)
were added. The mixture was heated to 45e50 ꢀC for a further 1 h,
with additional ethanol added as needed to dissolve any pre-
cipitate. The aqueous layer was saturated with potassium carbon-
ate, and extracted with diethyl ether (3ꢂ20 mL). The combined
organic extracts were then washed with brine and distilled water,
and dried (MgSO4), filtered and the solvents evaporated in vacuo to
give the crude product (55% yield by GC analysis using tetradecane
as an internal standard). A sample was purified by column chro-
matography on neutral aluminium oxide (hexane, followed by 2:1
hexane: diethyl ether) to give pure racemic 4 as a viscous yellow oil/
semi-solid; Rf¼0.54 (1:2 diethyl ether/hexane); vmax (neat/cmꢁ1):
3584 (OH), 1612 (C]C); dH (400 MHz; CDCl3): 7.05 (2H, d, J¼8.6 Hz,
CH), 6.75 (2H, d, J¼8.6 Hz, CH), 3.70 (3H, s, CH3), 2.60 (2H, app t,
J¼8.9 Hz, CH2), 2.30e0.90 (12H, m, CH, CH2), 0.85e0.80 (12H, m,
CH3); dC (125 MHz; CDCl3): 158.1 (quat C),135.8 (quat C),129.5 (CH),
114.3 (CH), 80.7 (quat C), 55.7 (CH3), 47.7 (quat C), 44.5 (CH), 38.8
(CH2), 33.7 (CH), 31.8 (CH2), 25.7 (CH2), 21.7 (CH2), 20.7 (CH3), 20.5
(CH3); UVꢁvis lmax: 228 nm; HRMS; EI m/z: calcd for C21H34O2
318.2559, found 318.2548 (Mþ, 100%).
4.4. Reaction of imidoyl chlorides 7e9 with the cyanoborate
from mixed trialkylborane 3
Imidoyl chlorides 7e9 were reacted with the cyanoborate from
mixed trialkylborane 3 in a similar manner as for imidoyl chloride 1,
giving various amounts of 5 and 6 by 1H NMR analysis of the crude
product following work-up (Table 1).
4.5. Reaction of imidoyl chloride 7 with the cyanoborate from
mixed trialkylborane 3 (excess 1-octene)
General procedure 1 was repeated using imidoyl chloride 7;
however, before addition of the TFAA, 1-octene (2.35 mL,
15.0 mmol) was added, and the reaction mixture was heated to
100 ꢀC for 6 h. TFAA was then added as before, and the procedure
was identical thereafter. 1H NMR analysis of the crude product
(1.71 g) showed the presence of excess 1-octene and 5 (in a 79:21
ratio, respectively, corresponding to a 61% yield of 5, by relative
integrations in the 1H NMR spectrum), but no trace of 6, tert-alcohol
arising from n-octyl group migration, thexanol or 1-octanol was
present.
4.6. Reaction of imidoyl chloride 7 with the cyanoborate from
mixed trialkylborane 3 (acetaldehyde)
4.3. General procedure 1. Reaction of imidoyl chloride 1 with
mixed trialkylborane 3
General procedure 1 using imidoyl chloride 7 was repeated to
the point until the reaction with imidoyl chloride 7 was complete.
Acetaldehyde (0.56 mL, 10.0 mmol) was added drop-wise by sy-
ringe, and the solution left to stir at rt for 36 h. Excess acetaldehyde
was removed under a fast stream of N2, and a solution of n-BuLi in
hexanes (1.45 M, 3.45 mL, 5.0 mmol) was added drop-wise with
vigorous stirring at ꢁ78 ꢀC. The addition of TFAA and subsequent
An oven dried three-necked flask equipped with a magnetic
stirrer bar, stopcock, and septum was set up. Dry potassium cyanide
(0.342 g, 5.5 mmol) was ground up prior to use with a pestle and
mortar, and transferred into a bent side arm closed at one end, and

D.H. Jones et al. / Tetrahedron 71 (2015) 6285e6289
6289
steps were then carried out as in general procedure 1. Analysis of
the crude product by 1H NMR spectroscopy showed only ketone 5,
with no presence of alkene 6 or tert-alcohol arising from migration
of the n-butyl group.
a mixture of isomers (Z)/(E): 88:12 by relative integrations in the 1H
NMR spectrum (14c, 0.12 g, 10%) as a colourless oil; Rf¼0.91 (4:1
hexane/ethyl acetate); vmax (neat/cmꢁ1): 3004 (alkene CH); (NMR
spectra were consistent with those reported for (Z)-heptadec-8-
ene);27 LRMS; EIþ m/z (%): 238 (Mþ, 45%), 119 (100), 111 (21), 97
(44), 84 (100), 71 (100), 57 (100); di-n-octyl ketone, (13a/c, 0.23 g,
18%), Rf¼0.8 (4:1 hexane/diethyl ether); and di-n-octylthex-
ylmethanol11 (12c, 0.26 g, 15%) as a yellow oil; Rf¼0.63 (4:1 hexane/
ethyl acetate); vmax (neat/cmꢁ1): 3533 (OH); dH (400 MHz; CDCl3):
1.80 (1H, app sep, J¼6.8 Hz, CH), 1.58e1.42 (4H, m, CH2), 1.30e1.10
(24H, m, CH2), 0.85 (6H, d, J¼6.8 Hz, CH3), 0.80 (6H, t, J¼6.7 Hz,
CH3), 0.75 (6H s, CH3); dC (125 MHz; CDCl3): 79.6 (quat C, COH), 43.7
(quat C), 36.4 (CH2), 32.8 (CH), 31.9 (CH2), 30.8 (CH2), 29.6 (CH2),
29.3 (CH2), 25.0 (CH2), 22.7 (CH2), 20.3 (CH3), 20.1 (CH3), 14.0 (CH3);
HR EIþ-MS m/z (%): calculated for C23H47 323.3678, found 323.3663
(MþꢁOH, 28%).
4.7. Substrate scope reaction (i)
An oven dried three-necked flask equipped with a magnetic
stirrer bar, stopcock, and septum was set up. Dry potassium cyanide
(0.342 g, 5.5 mmol) was ground up prior to use with a pestle and
mortar, and transferred into a bent side arm closed at one end, and
was fitted to the remaining neck of the flask. The flask was flushed
with N2 for 10 min, and cooled to 0 ꢀC. Borane-SMe2 complex
(10.0 M, 0.5 mL, 5.0 mmol) was added, followed by the drop-wise
addition of 1-octene (2.33 mL, 15.0 mmol). Following completion
of addition, the solution was warmed to rt and was left to stir for
3 h. Imidoyl chloride 7 was introduced as a solution in dry diglyme
(1.43 g in 6 mL); the procedure thereafter was identical to general
procedure 1. The crude product was purified by column chroma-
tography on neutral alumina (hexane, followed by 3:1 hexane:
diethyl ether) to give di-n-octyl ketone15 (13a, 0.22 g, 17%) as col-
ourless sheets; mp 49e50 ꢀC (lit. 48e48.5 ꢀC15); Rf¼0.8 (4:1 hex-
ane/diethyl ether); vmax (neat/cmꢁ1): 1706 (C]O); dH (400 MHz;
CDCl3): 2.37 (4H, t, J¼7.5 Hz, CH2C]O), 1.59e1.48 (4H, m, CH2),
1.32e1.16 (20H, m, CH2), 0.87 (6H, t, J¼6.8 Hz, CH3); dC (125 MHz;
CDCl3): 211.8 (quat C, C]O), 42.8 (CH2, CH2C]O), 31.8 (CH2), 29.4
(CH2), 29.3 (CH2), 29.2 (CH2), 23.9 (CH2), 22.6 (CH2), 14.1 (CH3); LR
CIMS m/z (%): 296 (Mþ þCH3CN, 100%); and tri-n-octylmethanol
(12a, 0.90 g, 49%),11 as a colourless oil; Rf¼0.57 (1:1 diethyl ether/
hexane); vmax (neat/cmꢁ1): 3390 (OH); dH (400 MHz; CDCl3): 5.75
(1H, s, OH), 1.40e1.20 (42H, m, CH2), 0.80 (9H, t, J¼6.0, CH3); dC
(125 MHz; CDCl3): 74.4 (quat C, COH), 39.8 (CH2), 32.8 (CH2), 31.8
(CH2), 29.8 (CH2), 29.7 (CH2), 23.9 (CH2), 23.1 (CH2), 14.2 (CH3);
LRMS; EI m/z (%): 350 (MþꢁOH, 62%), 255 (100), 237 (41), 154 (94),
139 (100), 126 (53), 111 (96), 97 (100), 69 (98).
4.10. Substrate scope reaction (iv)
The procedure for substrate scope reaction (i) was repeated
using mixed trialkylborane 3 (see general procedure 1) to give the
crude products, which were separated by column chromatography
on silica (hexane) to give 5 (0.058 g, 5% yield) and 6 (0.59 g, 55%
yield).
Acknowledgements
D.H. Jones thanks the Engineering and Physical Sciences Re-
search Council and Cardiff University for a studentship. G. A. El-Hiti
extends his appreciation to the Deanship of Scientific Research at
King Saud University for its funding for his research through the
research group project RGP-VPP-239.
References and notes
1. Aggarwal, V. K.; Fang, G. Y.; Ginesta, X.; Howells, D. M.; Zaja, M. Pure Appl. Chem.
2006, 78, 215e229.
4.8. Substrate scope reaction (ii)
2. Brown, H. C.; Imai, T. J. Org. Chem. 1984, 49, 892e898.
3. Brown, H. C.; Singh, S. M.; Rangaishenvi, M. V. J. Org. Chem. 1986, 51, 3150e3155.
4. Sonawane, R. P.; Jheengut, V.; Rabalakos, C.; Larouche-Gauthier, R.; Scott, H. K.;
Aggarwal, V. K. Angew. Chem., Int. Ed. 2011, 50, 3760e3763.
5. Smith, K.; Elliott, M. C.; Jones, D. H. J. Org. Chem. 2013, 78, 9526e9531.
6. Elliott, M. C.; Smith, K.; Jones, D. H.; Hussain, A.; Saleh, B. A. J. Org. Chem. 2013,
78, 3057e3064.
7. Soundararajan, R.; Li, G.; Brown, H. C. Tetrahedron Lett. 1994, 35, 8957e8960.
8. Bonet, A.; Odachowski, M.; Leonori, D.; Essafi, S.; Aggarwal, V. K. Nat. Chem.
2014, 6, 584e589.
9. Brown, H. C.; Rathke, M. W. J. Am. Chem. Soc. 1967, 89, 2737e2738.
10. Pelter, A.; Rao, J. M. J. Organomet. Chem. 1985, 285, 65e69.
11. Pelter, A.; Hutchings, M. G.; Rowe, K.; Smith, K. J. Chem. Soc., Perkin Trans. 11975,
138e142.
12. Brown, H. C.; Carlson, B. A. J. Org. Chem. 1973, 38, 2422e2424.
13. Pelter, A.; Hutchings, M. G.; Smith, K. J. Chem. Soc., Perkin Trans. 11975, 142e145.
14. Pelter, A.; Hutchings, M. G.; Smith, K.; Williams, D. J. J. Chem. Soc., Perkin Trans. 1
1975, 145e150.
The procedure for substrate scope reaction (i) was repeated
using tricyclopentylcyanoborate (5.0 mmol). Separation of the
components by column chromatography on neutral alumina (4:1
hexane: diethyl ether) gave dicyclopentyl ketone15 (13b, 0.249 g,
29%, contaminated with 4% cyclopentylmethylenecyclopentane) as
a colourless oil; Rf¼0.70 (3:1 hexane/diethyl ether); vmax (neat/
cmꢁ1): 1705 (C]O); dH (400 MHz; CDCl3): 2.96e2.85 (2H, m, CH),
1.81e1.41 (16H, m, CH2); dC (125 MHz; CDCl3): 216.0 (quat C, C]O),
50.7 (CH), 26.1 (CH2), 25.2 (CH2); LRMS; EIþ m/z (%): 166 (Mþ, 24%),
97 (98), 69 (100); and tricyclopentylmethanol (12b, 0.41 g, 39%),26
as a light yellow oil; Rf¼0.48 (3:1 hexane/diethyl ether); vmax (neat/
cmꢁ1): 3522 (OH); dH (400 MHz; CDCl3): 2.13e1.97 (3H, m, CH),
1.64e1.25 (24H, m, CH2); dC (125 MHz; CDCl3): 77.6 (quat C, COH),
47.9 (CH), 27.9 (CH2), 25.2 (CH2); LR EIMS m/z (%): 218 (MþꢁH2O,
5%), 149 (100), 107 (27), 81 (82), 67 (73)
15. Pelter, A.; Smith, K.; Hutchings, M. G.; Rowe, K. J. Chem. Soc., Perkin Trans. 11975,
129e138.
16. Carlson, B. A.; Brown, H. C. J. Am. Chem. Soc. 1973, 95, 6876e6877.
17. Katz, J. J.; Carlson, B. A.; Brown, H. C. J. Org. Chem. 1974, 39, 2817e2818.
18. Hegarty, A. F.; Cronin, J. D.; Scott, F. L. J. Chem. Soc., Perkin Trans. 1 1975,
429e435.
4.9. Substrate scope reaction (iii)
19. Brown, H. C.; Rao, B. C. S. J. Am. Chem. Soc. 1959, 81, 6434e6437.
20. Brown, H. C.; Jadhav, P. K.; Desai, M. C. J. Am. Chem. Soc. 1982, 104, 4303e4304.
21. Brown, H. C.; Zweifel, G. J. Am. Chem. Soc. 1960, 82, 4708e4712.
22. Elliott, M. C.; Smith, K. Organometallics 2013, 32, 4878e4881.
23. Tamura, K.; Mizukami, H.; Maeda, K.; Watanabe, H.; Uneyama, K. J. Org. Chem.
1993, 58, 32e35.
24. El-Hiti, G. A.; Smith, K.; Jones, D. H.; Masmali, A.; Kariuki, B. M. Sect. E.-Struct
Rep. Online Acta Crystallogr. 2013, 69, o1384.
25. Cherney, A. H.; Reisman, S. E. Tetrahedron 2014, 70, 3259e3265.
26. Smith, K.; Balakit, A. A.; El-Hiti, G. A. Tetrahedron 2012, 68, 7834e7839.
27. Ko, E. J.; Savage, G. P.; Williams, C. M.; Tsanaktsidis, J. Org. Lett. 2011, 13,
1944e1947.
2,3-Dimethyl-2-butene (0.63 g, 7.5 mmol) was added drop-wise
to neat borane-dimethyl sulfide (10.0 M, 5.0 mmol) at 0 ꢀC, and
then the reaction mixture was left to stir for 2 h. Dry THF (5 mL) was
added, followed by the drop-wise addition of 1-octene (1.57 mL,
10 mmol). The reaction mixture was left to stir for 2 h at 0 ꢀC. The
procedure thereafter was the same as substrate scope reaction (i) to
give the crude products, which were separated by column chro-
matography on neutral alumina (hexane, followed by increasingly
polar diethyl ether/hexane eluents) to give heptadec-8-ene as