An improved synthesis route to functionalized 2-alkyn-1-ylboronates: Useful intermediates for the preparation of α-allenic alcohols

Article abstract of DOI:10.1007/s00706-007-0769-0

Functionalized 2-alkyn-1-ylboronates were successfully prepared in good yields by reacting various acyclic and cyclic (iodomethyl)boronates with various alkynyllithium salts. Amongst various (iodomethyl)boronates studied, 2-(iodomethyl)-1,3,2-dioxa-4,4,5,5-tetramethylborolane provided improved chemical yields of 2-alkyn-1-ylboronates with pyran- and triisopropylsilyl- substituted alkynyllithium salts. 2-Alkyn-1-ylboronate bearing an acid sensitive structure (pyran) was successfully synthesized which would be very difficult to achieve under previously reported reaction conditions. The exceptionally rapid rearrangement of the "ate" complex derived from the pinacol (iodomethyl)boronate, suppression of the side product formation, and the stability of the pinacol 2-alkyn-1-ylboronate are some of the notable merits of this protocol. This new procedure offers a simple and convenient alternative route to the existing methodologies, in terms of the milder reaction conditions, functional group compatibility, and the ease of the operation. The synthesis scope of this class of 2-alkyn-1-ylboronates was demonstrated by reacting the pinacol 2-alkyn-1-ylboronate with benzaldehyde, which yielded the α-allenic alcohol in good yield and regioselectivity.

Full text of DOI:10.1007/s00706-007-0769-0

Monatsh Chem 139, 241–249 (2008)
DOI 10.1007/s00706-007-0769-0
Printed in The Netherlands
An Improved Synthesis Route to Functionalized 2-Alkyn-1-ylboronates:
Useful Intermediates for the Preparation of a-Allenic Alcoholsy
Chandra D. Roy1;2;ꢀ, Raman Soundararajan1, and Herbert C. Brown1
1
H. C. Brown Center for Borane Research, Department of Chemistry, Purdue University, IN, USA
2
EMD Biosciences Inc., San Diego, CA, USA
Received July 14, 2007; accepted July 22, 2007; published online February 1, 2008
# Springer-Verlag 2008
and propargylic alcohols have been utilized exten-
sively not only as building blocks for the synthesis of
biologically active molecules such as (ꢁ)-9-deoxy-
goniopypyrone [2], 3-deoxy-D-glycero-D-galacto-2-
ulosonic acids (KDN) [3], mono-THF acetogenins
[4], and an immunosuppressant discodermolide [5],
but also in coupling reactions [6] and in ene-yne
metathesis [7]. Conceptually, the most attractive
method appears to be the regiospecific addition of
allenyl and propargyl nucleophiles to carbonyls, but
these metal-mediated propargylation=allenylation suf-
fer from regioselectivity due to the metallotropic re-
arrangement of these species and nonregiospecific
addition to electrophiles [8]. A highly efficient trans-
formation of an organotin intermediate into propar-
gylboron reagent in excellent isomeric purity was
reported by Corey and co-workers [9]. An insertion
of a CH2 group between the carbon and boron atom
of the C–B bond, via in situ generation and capture of
(halomethyl)lithiums, LiCH2X, has proven to be a
very important methodology for a variety of synthet-
ic transformations [10]. One of the salient features of
this one-carbon homologation is that the rearrange-
ment of the initially formed ‘‘ate’’ complex takes
place with absolute stereochemical integrity, which
makes it a highly valuable reaction for general asym-
metric syntheses utilizing organoboranes.
Summary. Functionalized 2-alkyn-1-ylboronates were suc-
cessfully prepared in good yields by reacting various acyclic
and cyclic (iodomethyl)boronates with various alkynyllithium
salts. Amongst various (iodomethyl)boronates studied, 2-
(iodomethyl)-1,3,2-dioxa-4,4,5,5-tetramethylborolane provid-
ed improved chemical yields of 2-alkyn-1-ylboronates with
pyran- and triisopropylsilyl-substituted alkynyllithium salts.
2-Alkyn-1-ylboronate bearing an acid sensitive structure (py-
ran) was successfully synthesized which would be very diffi-
cult to achieve under previously reported reaction conditions.
The exceptionally rapid rearrangement of the ‘‘ate’’ complex
derived from the pinacol (iodomethyl)boronate, suppression of
the side product formation, and the stability of the pinacol
2-alkyn-1-ylboronate are some of the notable merits of this
protocol. This new procedure offers a simple and convenient
alternative route to the existing methodologies, in terms of the
milder reaction conditions, functional group compatibility, and
the ease of the operation. The synthesis scope of this class of
2-alkyn-1-ylboronates was demonstrated by reacting the pina-
col 2-alkyn-1-ylboronate with benzaldehyde, which yielded
the ꢀ-allenic alcohol in good yield and regioselectivity.
Keywords. 2-Alkyn-1-ylboronates; (Iodomethyl)boronates;
Alkynyllithium salts; ꢀ-Allenic alcohol.
Introduction
The synthetic applications of allyl-, allenyl-, and
propargylboranes are well recognized [1]. Allenyl
yDedicated to my mentor, Professor Herbert C. Brown, who
passed away on December 19, 2004 (1912–2004). The work
described herein was carried out at Purdue University during
my stay as a post-doctoral research associate (1995–2001)
Matteson et al. found that the LiCH2Br was a
much superior reagent compared to that of LiCH2Cl,
which suffers from certain problems, such as low
reactivity and occasional ꢁ-elimination and oxygen
ꢀ
Corresponding author. E-mail: chandra0919@gmail.com

242
C. D. Roy et al.
Fig. 1. Generation of a common ‘‘ate’’ complex
migration [11]. Wallace and Zong were able to im-
prove the chemical yield of homologated boronic
ester derived from D2-isoxazolines when LiCH2I
was generated from CH2I2 and MeLi, instead of
n-BuLi [12]. Encouraged by this unique behavior
of LiCH2I carbenoid, a systematic study was under-
taken to compare the relative reactivities of all the
three (halomethyl)lithium reagents (LiCH2X; X ¼ Cl,
Br, and I) with a wide variety of boronic esters in this
laboratory [13]. This study revealed significant dif-
ferences in reactivities, especially with alkenyl- and
alkynylboronates. Alkynylboronates reacted much
faster with LiCH2I while the alkenylboronates ex-
hibited little difference in rates among all three
(halomethyl)lithiums. This unique reactivity of alkyn-
1-ylboronates due to the nature of the alkynyl-boron
bonds in the ‘‘ate’’ complex is quite contrast to other
classes of boronates, such as, alkyl-, alken-1-yl-, and
arylboronates [14]. Later, a new general procedure
for the preparation of higher propargylboronates in
excellent isomeric purity (Fig. 1, Route A) was de-
veloped [15]. This successful synthesis of 2-alkyn-1-
ylboronates was based on one-carbon homologation
strategy. This method has certain limitations, such
as, preparation of an individual starting alkynylbor-
onates [16], avoidance of alkynylboronates bearing
acid-sensitive functionalities (due to HCl treatment),
significant formation of side products, and the in-
stability of the acyclic propargylboronates. In view
of the importance of propargylboronates in organic
synthesis, it was of considerable interest to develop
a practical, convenient, and general procedure. We
reported a highly general procedure for the prepa-
ration of 2-alkyn-1-ylboronates in our preliminary
communication (Fig. 1, Route B) [17] and herein
present a detailed study of reactions of acyclic and
cyclic (iodomethyl)boronates with various function-
alized alkynyllithium salts.
Results and Discussion
Selection of Various (Iodomethyl)boronates 1–4
Reactions of alkynyllithium salts (generated in situ
from the corresponding alkynes and LDA) with di-
isopropyl (iodomethyl)boronate would essentially
produce an ‘‘ate’’ complex identical to the one formed
in the previously reported procedure, which eventu-
ally would be expected to rearrange to the corre-
sponding propargylboronates (Fig. 1). This strategy
avoids the synthesis of an individual functionalized
alkynylboronate (starting substrate). The commer-
cially available functionalized alkynes can be used
directly to generate alkynyllithium salts in situ in a
Fig. 2. Various (iodomethyl)boronates 1–4

Functionalized 2-Alkyn-1-ylboronates
243
Fig. 3. Reaction of triisopropyl borate with carbenoid, LiCH2I
single pot. Considering the stability of cyclic bo-
ronic esters, it was desirable to examine both acy-
clic and cyclic boronates (Fig. 2) [18]. Also, the
selection of (iodomethyl)boronates was based on
the literature report because the ‘‘ate’’ complex de-
rived from alkynylboronate and LiCH2I provided
results superior to those achieved with LiCH2Br
and LiCH2Cl [13].
Reactions of Diisopropyl (Iodomethyl)boronate
(1) with Various Alkynyllithium Salts
Diisopropyl (iodomethyl)boronate (1) (11B NMR at
ꢂ ¼ 7.5 ppm) was treated with in situ generated al-
kynyllithium salt at ꢃ78ꢂC in THF (Fig. 4). The cap-
ture of alkynyllithium salt was almost instantaneous
leading to the formation of the intermediate ‘‘ate’’
complex (11B NMR at ꢂ ¼ ꢃ2.0 to þ2.0 ppm), which
then slowly rearranged to the propargylboronate. The
progress of the reaction was easily monitored by 11B
NMR with the disappearance of the ‘‘ate’’ complex
peak and the appearance of the product propargylbor-
onate peak (ꢂ ¼ þ27.0 ppm). These higher propargyl-
boronates could not be isolated and characterized due
to their inherent labile nature. Therefore, these pro-
pargylboronates were oxidized to propargylic alcohols
with alkaline H2O2 and characterized spectroscopi-
cally (Fig. 5). The results obtained with representative
alkynyllithium salts are summarized in Table 1.
This methodology appeared to be highly general
accommodating alkynes bearing representative func-
tional groups. It was important to note that the gen-
eration of the ‘‘ate’’ complex at 0ꢂC, instead of, at
ꢃ78ꢂC, had little or no effect on the chemical yields
of the propargylboronates, while greatly simplifying
the experimental procedure. Formation of the ‘‘ate’’
complex was quantitative, with the moderately lower
yields of the products due to the parallel formation
Preparation of Diisopropyl (Iodomethyl)boronate (1)
Previously, diisopropyl (iodomethyl)boronate (1) was
prepared from triisopropyl borate and in situ gener-
ated LiCH2I using n-BuLi in only 70% chemical
yield [19]. The use of MeLi significantly improved
the chemical yield of diisopropyl (iodomethyl)bo-
ronate (>92.4% based on 11B NMR after dry HCl
treatment). The isolated yield was >80% after distil-
lation under reduced pressure (Fig. 3). Formation of
side product n-BuI (bp ¼ 130–131ꢂC) and unreacted
starting borate always contaminated the product dur-
ing fractional distillation. The use of MeLi in place
of n-BuLi not only improves the chemical yield
(>90%) of the diisopropyl (iodomethyl)boronate but
also makes the purification step easier. The MeLi
procedure produces MeI which being a very low
boiling liquid (bp ¼ 41–43ꢂC) makes the fractional
distillation simpler.
Fig. 4. Reactions of diisopropyl (iodomethyl)boronate (1) with various alkynyllithium salts

244
C. D. Roy et al.
Fig. 5. Various propargylic alcohols 5–14
decomposition of the product, propargylboronate.
On the other hand, the pure 2-alkyl-1-ylboronate
completely transformed to the undesired side prod-
uct (ꢂ ¼ 17.5 ppm) when heated to 65ꢂC for few
hours. The completely converted undesired side
product upon alkaline hydrogen peroxide oxidation
yielded an unidentified sticky polymeric material
that did not show any carbonyl or hydroxyl frequen-
cies in IR spectrum. In the case of (triisopropylsilyl)-
acetylene, the rearrangement of the ‘‘ate’’ complex
was observed to be much slower than other acety-
lenes, which contributed to the formation of more
undesired side product. The side product appeared
to build up by the destruction of main product, pro-
pargylboronates. In another experiment, an alkynyl-
lithium salt was generated separately at ꢃ78ꢂC and
was added to the (iodomethyl)boronic ester to form
the ‘‘ate’’ complex, hoping to avoid any parallel re-
actions, such as, the possible coordination of LDA
with boronate. Unfortunately, the experimental result
showed no improvement in the chemical yield.
Table 1. Reactions of diisopropyl (iodomethyl)boronate (1)
with various alkynyllithium saltsa via reactions shown in Fig. 4
Entry RCꢅCCH2B(OiPr)2 Time=
Yield of
RCꢅCCH2OH
(R)
h
after oxidation=%b–c
1
2
3
4
5
6
7
8
9
n-C4H9
2.0
2.0
2.5
3.0
1.5
3.5
3.0
22.0
65
63
80
66
64
80
62
53
45
(CH3)2CHCH2
(CH3)3Cc
n-C8H17
C5H9
Cl(CH2)3
2-(CH2CH2O)pyran
[(CH3)2CH]3Si
CH3O2C(CH2)8
1.75
a
1.10 Equiv. of the reagent used
Yields based on the 1H NMR analyses of the alcohols pro-
b
duced by the oxidation of the propargylboronates with alka-
line hydrogen peroxide using biphenyl as the internal standard
c
Isolated yields were 3–5% lower than their NMR yields
of a side product (11B NMR at ꢂ ¼ 17.5 ppm). Earlier,
we had made few attempts to characterize the side
product, but without success [15]. The persistence
of such impurity even after hydrolysis clearly ruled
out the possibility of any tricoordinated borate spe-
cies. The absence of a carbonyl stretching frequen-
cy (ꢃꢀC¼O ꢄ 1720 cmꢃ1) and an allenic frequency
(ꢃꢀC¼C¼C ꢄ 1930 cmꢃ1) in IR spectrum of the crude
propargylic alcohol also eliminated the presence of
any allenic intermediate possibly formed by the 1,3-
rearrangement of the initially formed 2-alkyn-1-
ylboronates (IR absorptions for propargylboronates:
Table 2. Reactions of 2-(iodomethyl)-1,3,2-dioxaborinane
(2) with various alkynyllithium saltsa
Entry
RCꢅCCH2B-
Time=
h
Yield of
RCꢅCCH2OH
[(OCH2)2CH2] (R)
after oxidation=%b,c
1
2
3
n-C8H17
2-(CH2CH2O)pyran
[(CH3)2CH]3Si
2.5
3.5
3.5
53
45
65
a
1.10 Equiv. of the reagent used
Yields based on the 1H NMR analyses of the alcohols pro-
ꢃꢀCꢅC ꢄ 2220 cmꢃ1 and allenylboronates: ꢃꢀC¼C¼C
ꢄ
b
1925 cmꢃ1). The product undergoes complete de-
composition in <2 days at room temperature. A
sample kept at 0ꢂC for several days showed little
duced by the oxidation of the propargylboronates with alka-
line hydrogen peroxide using biphenyl as the internal standard
c
Isolated yields were 3–5% lower than their NMR yields

Functionalized 2-Alkyn-1-ylboronates
245
Our next objective was essentially to improve the
chemical yields of the various propargylboronates
and simultaneously suppress the formation of the
undesired side products. Our detailed study on the
relative stability of various boronic esters employing
transesterification suggested that a library of rela-
tively more stable (iodomethyl)boronates could be
synthesized from acyclic diisopropyl (iodomethyl)-
boronate (1) by simple transesterification with the
desired diols [20]. Three cyclic (iodomethyl)boro-
nates, 2-(iodomethyl)-1,3,2-dioxaborinane (2), 2-
(iodomethyl)-1,3,2-dioxa-5,5-dimethylborinane (3),
and 2-(iodomethyl)-1,3,2-dioxa-4,4,5,5-tetramethyl-
borolane (4), were prepared by transesterification
of diisopropyl (iodomethyl)boronate (1) with the
corresponding diols in dry n-pentane in almost quan-
siderably, but not completely. Only 5–6% of the side
product (11B NMR at ꢂ ¼ 17.5 ppm) could be ob-
served after 1.5 h. To ensure the quantitative cap-
ture of boronate with alkynyllithium salt, LDA was
added at ꢃ78ꢂC and the 11B NMR spectrum was
recorded immediately. After 0.5 h, 11B NMR spec-
trum showed the complete absence of the starting
boronate (11B NMR at ꢂ ¼ 28.5 ppm). Surprisingly,
the chemical yields of the desired products did not
improve substantially. We had observed the drop in
chemical yield by 10% when the ‘‘ate’’ complex
derived from 1,3-propanediol heptyn-1-ylboronate
(81%) was used in place of diisopropyl heptyn-1-
ylboronate (91%) with LiCH2I. 2-(Iodomethyl)-
1,3,2-dioxa-5,5-dimethylborinane (3) also provided
results (comparable chemical yields) similar to those
obtained from 2-(iodomethyl)-1,3,2-dioxaborolane
(2) with representative alkynyllithium salt. Although
the rearrangement of the ‘‘ate’’ complex was slightly
faster than its unsubstituted analog, the formation of
the side product (5–6%) could not be completely
suppressed in this case also.
1
titative yields and identified by 11B, H, and 13C
NMR spectroscopy.
The ‘‘ate’’ complexes derived from 2-(iodo-
methyl)-1,3,2-dioxaborinane (2) and alkynyllithium
salts rearranged to propargylboronates at 0ꢂC much
faster than the corresponding acyclic diisopropyl
(iodomethyl)boronate (1) (Table 2). In the case of
1-decyne, more than 60% rearrangement of the ‘‘ate’’
complex (ꢂ ¼ ꢃ2 to þ2 ppm) to propargylboronate
(ꢂ ¼ þ28.5 ppm) was complete in <5 min in the
probe of NMR spectrometer whereas the ‘‘ate’’ com-
plex derived from diisopropyl (iodomethyl)boronate
did not show any appreciable amount of rearranged
product in 5 min (ꢆ25% in 20 min). The ‘‘ate’’ com-
plex derived from (triisopropylsilyl)acetylene rear-
ranged relatively slowly (50% in 0.5 h). The ‘‘ate’’
complex derived from 2-(3-butynyloxy)tetrahydro-
2H-pyran rearranged 50% in <5 min. Interestingly,
the formation of side product was suppressed con-
Reactions of 2-(Iodomethyl)-1,3,2-dioxa-4,4,5,5-
tetramethylborolane (4) with Various
Functionalized Alkynyllithium Salts
The ‘‘ate’’ complex derived from the pinacol (iodo-
methyl)boronate (4) rearranged slightly faster than
the ‘‘ate’’ complexes derived from cyclic (iodo-
methyl)boronates 2 and 3. More than 70–75% rear-
rangement was complete in 0.5 h in almost all the
cases (Fig. 6). Even the ‘‘ate’’ complex derived from
the (triisopropylsilyl)acetylene rearranged rapidly to
the desired propargylboronate (>60% in <5 min). We
Fig. 6. Reactions of 2-(iodomethyl)-1,3,2-dioxa-4,4,5,5-tetramethylborolane (4) with various alkynyllithium salts

246
C. D. Roy et al.
Table 3. Reactions of 2-(iodomethyl)-1,3,2-dioxa-4,4,5,5-
tetramethylborolane (4) with various alkynyllithium saltsa
via reactions shown in Fig. 6
ing both achiral and chiral propargylboronates using
our new methodology and study the diastereo- and
enantioselective addition of carbonyl compounds.
Unlike alken-1-yl- and allenylboronates, the pro-
pargylboronates appear to be much less reactive.
Benzaldehyde, being an active aldehyde, did not re-
act with the propargylboronate derived from 2-(iodo-
methyl)-1,3,2-dioxa-4,4,5,5-tetramethylborolane and
n-decynyllithium salt, at ꢃ78ꢂC (monitored by 11B
NMR). The reaction was found to be slow even at
0ꢂC. The reaction took 14–18 h for completion at
room temperature which upon oxidative workup af-
forded an ꢀ-allenic alcohol, 2-octyl-1-phenyl-2,3-
butadien-1-ol (15) in 60% chemical yield (Fig. 7).
Entry
RCꢅCCH2B-
Time=
h
Yield of
RCꢅCCH2OH
[OCH2C(CH3)2–]2 (R)
after oxidation=%b
1
2
3
4
5
n-C8H17
Cl(CH2)3
2-(CH2CH2O)pyran
[(CH3)2CH]3Si
CH3O2C(CH2)8
1.5
2.0
2.5
2.5
1.0
72
74
76
71
61
a
1.25 Equiv. of the reagent used
Yields based on the 1H NMR analyses of the alcohols pro-
b
duced by the oxidation of the propargylboronates with alka-
line hydrogen peroxide using biphenyl as the internal standard
1
The H NMR spectrum of the oxidized crude prod-
uct did not show any detectible amount of pro-
pargylic alcohol.
were pleased to note that the formation of side prod-
uct was completely suppressed. It was interesting to
note that the pinacol propargylboronate derived from
n-decynyllithium salt showed no significant deterio-
ration (<2%) even after 24 h at room temperature.
Significant improvements in chemical yields were
also noticed with pyran- and triisopropylsilylalky-
nyllithium salts. Gratifyingly, pinacol (iodomethyl)-
boronate (4) reacted rapidly with alkynyllithium salt
derived from undec-10-ynoic acid methyl ester. The
results of this study are summarized in Table 3.
Conclusions
To conclude, we developed a simple, convenient,
and general method for the preparation of a variety
of functionalized propargylboronates in good chem-
ical yields with excellent isomeric purity. The pres-
ent procedure has several advantages over the first
one. The second new methodology utilizes mild re-
agent, LDA (as compared to that of n-BuLi) that is
more beneficial for the functionalized boronic esters.
This procedure also avoids the necessity of making
individual cyclic and acyclic boronates. Various pro-
pargylboronates can simply be synthesized by just
using different alkynes. The mildness of the proce-
dure and the ability to run the reaction at ambient
Reaction of Pinacol Propargylboronate
with Benzaldehyde
After successful preparation of reasonably stable
propargylboronates, we were interested in synthesiz-
Fig. 7. Reaction of pinacol propargylboronic ester with benzaldehyde

Functionalized 2-Alkyn-1-ylboronates
247
ppm (It is usually difficult to observe the carbon atom ꢀ to
boron in a 13C NMR spectrum due to rapid quadruple-induced
relaxation).
conditions make it a simple and convenient alterna-
tive route for the large-scale reactions. Even an acid
sensitive group, e.g., acetal, which would be difficult
to accommodate using previously developed method-
ology (due to the utilization of dry HCl in the prep-
aration of starting alkyn-1-ylboronates), has been
accommodated. The formation of the undesired side
product, which could not be completely avoided in
the first procedure, has been suppressed. Pinacol pro-
pargylboronates have been found to be the most sta-
ble ones amongst cyclic and acyclic analogs. The
pinacol propargylboronate reacts with benzaldehyde
with excellent regioselectivity yielding the ꢀ-allenic
alcohol. This class of ꢀ-allenic alcohols is very use-
ful as intermediates in organic synthesis.
Preparation of Cyclic (Iodomethyl)boronates 2–4
Diisopropyl (iodomethyl)boronate (1) (5mmol) was mixed
with the corresponding diols (6.0–7.5 mmol) in dry n-pentane
and the mixtures were stirred at room temperature for 4–6 h.
Removal of n-pentane and 2-propanol under vacuum gave
crude products which was further dissolved in n-pentane and
excess of diols was removed by filtration under nitrogen at-
mosphere. Evaporation of solvent gave quantitative yields of
corresponding cyclic boronates. Products were purified by
distillation in vacuo. In the case of pinacol (iodomethyl)bor-
onate, excess pinacol was just removed by washing the reac-
tion mixture with water, because pinacol (iodomethyl)boronate
was found to be an unusually stable boronate to water.
2-(Iodomethyl)-1,3,2-dioxaborinane (2, C4H8BIO2)
1
11B NMR (CDCl3): ꢂ ¼ 28.30 ppm; H NMR (CDCl3): ꢂ ¼
Experimental
4.05 (t, 4H, ꢃOCH2ꢃ), 2.09 (s, ꢃCH2I), 1.96 (q, ꢃCH2ꢃ)
ppm; 13C NMR (CDCl3): ꢂ ¼ 62.30 (ꢃOCH2ꢃ), 20.97
(ꢃCH2ꢃ) ppm.
All air and moisture sensitive reactions were carried out under
1
nitrogen using oven-dried glassware. The 11B (96 MHz), H
(300 MHz), and 13C (75 MHz) NMR spectra were recorded on
a Varian Gemini NMR instrument, and the chemical shifts (ꢂ)
are given in ppm relative to external standard BF3–Et2O and
internal standards TMS and CDCl3 respectively. IR and Mass
spectra were recorded on Perkin Elmer 137 IR and Finnegan
mass spectrometers. THF was freshly distilled from sodium
benzophenone ketyl. MeLi, and LDA were purchased from the
Aldrich Chemical Co. All alkynes were purchased from the
Farchan Laboratories (except 4-methyl-1-pentyne which was
purchased from the Wiley Chemical Co.) and were used with-
out further purification. Higher propargyl alcohols were puri-
fied by column chromatography on silica gel except pyranyl
alcohol that was purified on neutral alumina.
2-(Iodomethyl)-1,3,2-dioxa-5,5-dimethylborinane
(3, C6H12BIO2)
11B NMR (CDCl3): ꢂ ¼ 27.99 ppm; 1H NMR (CDCl3): ꢂ ¼ 3.65
(s, 4H, ꢃOCH2ꢃ), 2.12 (s, ꢃCH2I), 1.00 (s, 6H, ꢃCH3) ppm.
2-(Iodomethy)-1,3,2-dioxa-4,4,5,5-tetramethylborolane
(4, C7H14BIO2)
1
11B NMR (CDCl3): ꢂ ¼ 31.70 ppm; H NMR (CDCl3): ꢂ ¼
2.16 (s, ꢃCH2I), 1.27 (s, 12H, ꢃCH3) ppm; 13C NMR
(CDCl3): ꢂ ¼ 84.17(–OCMe2–), 24.40 (–CH3) ppm.
Reactions of (Iodomethyl)boronates 1–4 with Various
Alkynyllithium Salts
Diisopropyl (iodomethyl)boronate (1, C7H16BIO2)
A solution of MeLi (1.40 M) in ethyl ether (100cm3,
140 mmol) was slowly added to a mixture of triisopropyl-
borate (32.3 cm3, 140 mmol) and diiodomethane (11.2 cm3,
140 mmol) in THF (75 cm3) at ꢃ78ꢂC while stirring. After
addition, the mixture was stirred at ꢃ78ꢂC for additional 0.5 h,
followed by quenching with anhydrous HCl in Et2O (150 cm3,
150 mmol). The cold bath was removed and the mixture was
allowed to warm up to room temperature for 1.25 h. The 11B
NMR spectrum showed 92% diisopropyl (iodomethyl)boro-
nate. Volatiles were removed using aspirator and the residue
was dissolved in n-pentane (100 cm3). The pentane soluble
part was transferred through cannula and the solid washed
with dry n-pentane (20 cm3). The combined pentane solution
was concentrated and the residue was distilled under reduced
pressure in the presence of copper wires (0.2cm long) to
afford a colorless liquid (30.2 g, 112 mmol) in 80% yield.
11B NMR (CDCl3): ꢂ ¼ 27.6ppm; 1H NMR (CDCl3): ꢂ ¼
4.39 (septet, J ¼ 6 Hz, 2H, ꢃOCH(CH3)2), 2.12 (s, ꢃCH2I),
1.19 (d, J ¼ 6 Hz, 12H, ꢃOCH(CH3)2) ppm; 13C NMR
(CDCl3): ꢂ ¼ 66.06 (ꢃOCH(CH3)2, 24.23 (ꢃOCH(CH3)2)
A representative procedure for the reaction of diisopropyl
(iodomethyl)boronate (1) with alkynyllithium salt. LDA
(2.2cm3, 3.3 mmol) was added slowly to a stirring solution
of diisopropyl (iodomethyl)boronate (1) (0.812 g, 3 mmol),
and n-decyne (0.60 cm3, 3.3 mmol) in THF (5cm3), cooled
to 0ꢂC under nitrogen atmosphere. The mixture was stirred
at 0ꢂC for 0.5–1.0 h, the cold bath was then removed and the
contents were allowed to warm to room temperature without
stirring for 3 h. The boronate was then oxidized with alkaline
hydrogen peroxide according to the usual procedure [21].
After adding biphenyl (0.0385 g, 0.25 mmol) and saturating
the aqueous layer with anhydrous K2CO3, the propargylic
alcohol was extracted with Et2O (3ꢇ30 cm3), dried, and
concentrated. The crude product was analyzed by 1H NMR
spectroscopy. The alcohol was purified by column chroma-
tography on silica gel (using 5–20% ethyl acetate=n-hex-
anes mixture) and the chemical yield of the isolated product
was also determined.
A representative procedure for the reaction of 2-(iodo-
methyl)-1,3,2-dioxa-4,4,5,5-tetramethylborolane (4) with alky-

248
C. D. Roy et al.
nyllithium salt: LDA (1.7cm3, 2.5 mmol) was added slowly to
a stirring solution of pinacol (iodomethyl)boronate 4 (0.536g,
2 mmol), and n-decyne (0.45 cm3, 2.5 mmol) in THF (5cm3),
cooled to 0ꢂC under nitrogen atmosphere. The mixture was
stirred at 0ꢂC for 0.5–1.0h, the cold bath was then removed
and the contents were allowed to warm to room temperature
without stirring for 1.5 h. The boronate was then oxidized with
alkaline hydrogen peroxide according to the usual procedure
[21]. After adding biphenyl (0.0385 g, 0.25 mmol) and saturat-
ing the aqueous layer with anhydrous K2CO3, the propargylic
alcohol was extracted with Et2O (3ꢇ30 cm3), dried, and con-
centrated. The crude product was analyzed by 1H NMR spec-
troscopy. The alcohol was purified by column chromatography
on silica gel (eluted with 5–20% ethyl acetate=n-hexanes
mixture) and the chemical yield of the isolated product was
also determined.
warm up to room temperature. After 6 h, 50% boronate peak
(ꢂ ¼ 31.93 ppm) was converted to borate peak (ꢂ ¼ 22.0ppm).
The reaction mixture was allowed to stir overnight, during
which almost all the boronate was transformed to the borate.
The borate was then oxidized with alkaline hydrogen peroxide
according to the usual procedure. The ꢀ-allenic alcohol was
extracted with Et2O (3ꢇ30cm3), dried, and concentrated. The
1
crude product was analyzed by H NMR spectroscopy. The
ꢀ-allenic alcohol, 3-octyl-1-phenyl-2,3-butadien-1-ol was pu-
rified by column chromatography on silica gel (eluted with 5–
20% ethyl acetate=n-hexanes mixture) and the chemical yield
(60%) of the isolated product was determined.
Colorless liquid; 1H NMR (CDCl3): ꢂ ¼ 7.50–7.20 (m, 5H,
ArH), 5.08 (m, Ph–CH(OH)ꢃ), 5.00 (m, ꢃC¼C¼CH2), 2.30–
1.10 (m, CH2¼C¼Cꢃ(CH2)7ꢃ), 0.85 (t, ꢃCH3) ppm; 13C
NMR (CDCl3): ꢂ ¼ 203.97, 142.10, 128.33, 127.78, 126.72,
108.31, 79.90, 74.08, 31.83, 29.37, 29.24, 28.88, 27.92, 27.45,
22.65, 14.11 ppm (1H and 13C NMR spectra were compared
with 2-butyl-1-phenyl-2,3-butadien-1-ol [8h]).
Spectral Data for Various Alkyn-2-yl-1-ols
Spectroscopic properties of hept-2-yl-1-ol 5 [22], 5-
methylhex-2-yl-1-ol [23], 4,4-dimethylpent-2-yn-1-ol [24],
undec-2-yn-1-ol [25], 6-chlorohex-2-yn-1-ol [26], 3-triisopro-
pylsilanylprop-2-yn-1-ol [27], 12-hydroxydodec-10-ynoic ac-
id methyl ester [28], and 12-hydroxydodec-10-ynoic acid [29]
are in accordance with those published in literature.
Acknowledgements
The financial supports from the National Science Foundation,
the Office of Naval Research, and the Purdue Borane Research
Fund are gratefully acknowledged.
3-(Cyclopentyl)prop-2-yn-1-ol (9, C8H12O)
Colorless liquid; IR (cmꢃ1, thin film): ꢃꢀ¼ 3300 (br, ꢃOH),
2230 (CꢅC) cmꢃ1; 1H NMR (CDCl3): ꢂ ¼ 4.25 (d, ꢃCH2OH),
2.60 (m, ꢃCH–CꢅCꢃ), 2.15 (br, s, ꢃOH), 1.90 (m, ꢃCH2ꢃ)
1.75–1.40 (m, 6H, ꢃCH2ꢃ) ppm; 13C NMR (CDCl3): ꢂ ¼
90.61, 77.89, 51.32, 33.72, 30.14, 24.96 ppm; MS (EI): m=z ¼
124 (Mþ), 67 (base); HRMS: m=z found 124.0892, calcd.
C8H12O 124.0888.
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