Direct, high-yielding, one-step synthesis of vic-diols from aryl alkynes

Article abstract of DOI:10.1016/j.tetlet.2018.01.041

An unprecedented, high yielding, direct, one-step synthesis of vic-diols from alkynes has been developed via metal-free, open-to-air dihydroboration with ammonia borane. The electronics of the alkyne and the reaction stoichiometry are critical for obtaining optimal yields of the 1,2-diol.

Full text of DOI:10.1016/j.tetlet.2018.01.041

Accepted Manuscript
Direct, high-yielding, one-step synthesis of vic-diols from aryl alkynes
P. Veeraraghavan Ramachandran, Michael P. Drolet
PII:
S0040-4039(18)30076-5
https://doi.org/10.1016/j.tetlet.2018.01.041
TETL 49628
DOI:
Reference:
Tetrahedron Letters
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Received Date:
Revised Date:
Accepted Date:
13 October 2017
21 December 2017
16 January 2018
Please cite this article as: Ramachandran, P.V., Drolet, M.P., Direct, high-yielding, one-step synthesis of vic-diols
from aryl alkynes, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.01.041
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Direct, high-yielding, one-step synthesis of
vic-diols from aryl alkynes
Leave this area blank for abstract info.
P. Veeraraghavan Ramachandran and Michael P. Drolet
1) H3NBH3 (2 equiv)
2 M THF, reflux, 1-2 h
2) [O]
HO
Ar
OH
R
Ar
R
(±)
54-83% yield

1
Tetrahedron Letters
journal homepage: www.els evier.com
Direct, high-yielding, one-step synthesis of vic-diols from aryl alkynes
P. Veeraraghavan Ramachandrana* and Michael P. Droleta
a Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
* E-mail address: chandran@purdue.edu Telephone: 765-494-5303
ARTICLE INFO
ABSTRACT
Article history:
Received
An unprecedented, high yielding, direct, one-step synthesis of vic-diols from alkynes has been
developed via metal-free, open-to-air dihydroboration with ammonia borane. The electronics of
the alkyne and the reaction stoichiometry are critical for obtaining optimal yields of the 1,2-diol.
Received in revised form
Accepted
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Ammonia borane
Hydroboration
Alkyne
1,2-diols
Open-flask
Hydroboration, discovered six decades ago, has become a
mainstay in organic syntheses.1 Despite involving pyrophoric
reagents requiring strictly anhydrous conditions, some with short
shelf lives, it has found myriad industrial-scale applications for
the preparation of valuable intermediates and target molecules. In
addition to the common borane reagents, borane-dimethyl sulfide
(BMS, 1) and borane-tetrahydrofuran (BTHF, 2), several mono-
and di-substituted alkyl-, alkoxy-, and haloboranes have been
developed for hydroboration.1 While the uncatalyzed addition of
B-H bonds to alkenes is common, the corresponding reaction of
alkynes has been restricted,2 mostly to those involving terminal
alkynes with hindered dialkylboranes.1,3
ketone and 1,2-diols, in low yields.6 All of these studies were
limited in the scope of substrates and conditions, providing low
amounts of vicinal diols.
Since these initial reports, there has been little effort9,10 to
examine the dihydroboration of alkynes in detail to provide broad
conclusions. As part of our program on amine-borane
chemistry,11 we recently reported the first open-flask, non-
dissociative hydroboration of alkenes with ammonia borane (AB,
3).12 To expand the utility of air and moisture stable 3 as a
hydroborating agent, alkynes were included as substrates to
possibly achieve the direct synthesis of valuable vicinal diols in
high yields.13 The fruitful results of this study follow (Scheme 1).
Ideally, the two unsaturations in alkynes can result in as many
hydroborations providing bi-functionalized molecules. On this
basis, the laboratories of Brown,4 Hassner,5 and Pasto6
independently examined the hydroboration of alkynes with
gaseous diborane or 2. With hex-1-yne and -3-yne as substrates,
Brown and Zweifel concluded that the hydroboration/oxidation
of internal aliphatic alkynes resulted in ketones, whereas those of
terminal alkynes formed hexan-1-ol via geminal diboro
intermediates. Altering the oxidation conditions, they achieved
54% yield of the corresponding aldehyde and small amounts (10-
12%) of the 1,2-diol.4,7 Subsequently, Brown developed the
hydroboration of terminal alkynes with dialkylboranes for
aldehyde synthesis, which has become a classic textbook
reaction. Hassner, on the other hand, examined the
hydroboration/oxidation of only an aromatic internal alkyne,
diphenylacetylene (4a), with a large excess of diborane bubbled
through tetrahydrofuran (THF), and reported the formation of
mixtures of hydrobenzoin (6a) and 1,2-diphenylethanol (7a) in
low yields.5,8 Pasto carried out deuterium labelling studies and
confirmed that terminal alkynes predominantly produce 1o-ols
and internal aromatic alkynes give roughly equal amounts of
Scheme 1. Hydroboration/oxidation of alkynes

2
Tetrahedron
The project was initiated with the hydroboration of a
for 1 h, was then applied to other alkynes, focusing initially on
aryl alkynes (Table 2).
representative internal alkyne, diphenylacetylene (4a) with
0.33 equiv 3, in THF at room temperature. 11B NMR
spectroscopic analysis of an aliquot of the reaction mixture
revealed no progress after 1 h. Gradual increase of the
temperature, followed by analysis showed that reaction occurred
only at reflux, when after 1 h, the 11B NMR spectrum revealed
the consumption of 3 and the presence of several overlapping
peaks centered at δ -5 ppm. This suggested the formation of
The steric and electronic environment on either side of the
alkyne was varied, proceeding from doubly aromatic-substituted
alkyne 4a to singly substituted phenylacetylene (4b) to a mixed
aryl alkyl substituted 1-phenylprop-1-yne (4c). The
corresponding products 6b and 6c were isolated
in 75% and 76% yields, respectively (Table 2, entries 2-3), with
only
the
racemic
anti-diol
Electron-deficient 4-fluorophenylacetylene
detected
for
(4d)
6c.14
and
polymeric4
alkylborane-ammonia
complexes,
attempted
separation of which failed. Nevertheless, purification of an
identical reaction after alkaline H2O2 oxidation afforded 57%
deoxybenzoin (5a) and 11% ( )-hydrobenzoin (6a), along with
19% of recovered 4a. The recovery of a large amount of 4a
prompted the examination of the effect of stoichiometry on the
reaction outcome (Table 1).
4-(trifluoromethyl)phenylacetylene (4e) were subjected to
hydroboration with 3 and diols 6d and 6e were isolated in 78%
yield each (Table 2, entries 4-5).
Table 2. 1,2-Dihydroboration and oxidation of alkynesa
Yield
(%)b
Entry
Alkyne (4)
Diol (6)
Time (h)
Table 1. Stoichiometry-controlled product distributiona
1
6a
1
78
2
3
6b
6c
1
1
75
76
3
(equiv.)
Recovery 4a
Yield5a
Yield 6a
(%)c
11
Entry
Timeb (h)
(%)c
19
3
(%)c
57
70
18
22
7
1
2
3
4
5
6
7
0.33
0.5
1
1
3
5
15
62
4
1
22
22
28
1
3
64
76
4
5
6d
6e
2
1
78
78
2
3
3
2
3
3
6
6
83
78
aConcentration with respect to 3. bTime required for complete consumption
of 3 by hydroboration or thermal decomposition as determined by 11B NMR
spectroscopy. cIsolated yield.
Increasing the equivalents of 3 to 0.5 resulted in an increased
yield of the ketone 5a (70%) and diol 6a (15%), with very little
recovery of 4a. Hydroboration-oxidation with one equivalent of 3
for 5 h yielded a drastically different product distribution of 18%
5a and 62% 6a, with negligible recovery of 4a. Prolonging the
reaction had no effect on the outcome. Isolation of significantly
larger quantity of the vicinal diol than previously reported
encouraged further increases in 3 to achieve maximum yield. We
hypothesized that an excess of 3 may be required for full
saturation of the triple bond since the vinylborane-ammonia
complex from the first hydroboration might be a slower
hydroborating reagent than 3 due to steric hindrance. Utilizing 2
equivalents of 3, gratifyingly, resulted in an improved yield of 6a
(76%, Table 1, Entry 5), supporting our assumption. Further
increase of 3 to 3 equivalents improved the yield, modestly, to
83% (Entry 6), while incurring an unacceptable loss to atom
economy. In all cases, only minimal (3-4% of the isolated diol)
meso-hydrobenzoin was detected. Thus, 2 equivalents of 3 was
chosen as optimal for further standardization.
6
7
6f
1
1
71
70
6g
8
9
6h
6i
1
2
68
54
O
4i
10
11
6j
1
1
36
53
6k
Reactions were also performed in several other etheric
solvents, such as 1,2-dimethoxyethane, 2-methyltetrahydrofuran,
diisopropyl ether, and dioxane, with no improvement in yield.14
The effect of the reagent concentration in THF was gauged and
2 M was deemed best, providing 6a in 79% yield. The presence
of excess reagent made it difficult to determine the time required
for completion by 11B NMR spectroscopy. Accordingly, 3 and 4a
were heated at reflux in THF for 1 h and worked up.
Gratifyingly, the product distributions remained the same (Table
1, Entry 7) as with the reaction performed for 22 h (Entry 5).
This optimal condition, 2 equivalents 3 in refluxing THF at 2 M
a Reagents and conditions: 3 (4 mmol), alkyne (2 mmol), THF (2 M) under
b
open-flask conditions. Isolated yield.
Adding a methyl substituent at the ortho- (4f), meta- (4g), and
para- (4h) positions of phenylacetylene provided the diols 6f-h
in 71%, 70%, and 68% yields, respectively (Table 2, entries 6-8).
This effect of the electron-donating group was even more
apparent for 4-methoxyphenylacetylene (4i), with the isolation of
only 54% of 6i (Table 2, Entry 9). We expected that even
electron-rich aliphatic alkynes would behave in a similar manner
to 4i.15 Indeed, when a terminal aliphatic alkyne dec-1-yne (4j)
was submitted to these conditions (Table 2, Entry 10), only 36%

3
of diol 6j was isolated with 48% of decan-1-ol (7j) as the major
product. This points to preferential geminal dihydroboration for
electron-rich alkynes as reported previously.4,6 Similarly,
dec-5-yne (4k) resulted in low yields (53%) of the racemic, anti-
( )-5,6-decanediol (6k).
In conclusion, we have demonstrated that ammonia
borane can be utilized for the dihydroboration of alkynes in THF
at reflux to provide vicinal diols in good yields. The formation of
the vicinal diols seems to rely on the stoichiometry and
electronics of the alkyne. Examination of other common
hydroborating agents, such as BTHF and BMS, established the
superiority of ammonia borane for the direct synthesis of diols
from alkynes. Considering the reported low yields of diols using
conventional hydroborating agents, we believe that the higher
temperature of the reaction also plays a major role in achieving
better yields. A one-pot reaction involving the in situ synthesis of
ammonia borane, was also very successful. The air and moisture
stability and ready availability18 of ammonia borane, as well as
the scope of diols in organic synthesis make this transformation a
valuable addition to the synthetic chemists’ arsenal.
The generality of the preference for vicinal
dihydroboration, as seen with 3, was explored by treating 4a with
other common hydroborating reagents (Table 3).
Table 3. Hydroboration with common hydroborating reagentsa
Entry
Borane
Yield 6a (%)b
1
2
3
4
5
6
7
8
H3B•NH3 (3)
H3B•SMe2 (1)c
H3B•THF (2)c
78
71
Acknowledgments
71
57
c
NaBH4/I2
NaBH4/(NH4)2SO4d
Chx2BH (8)c
Financial support from the Herbert C. Brown Center for
Borane Research is gratefully acknowledged.
83
42e
62g
12h
Chx2BH (8)c,f
tBuNH2•BH3 (9)
References and notes
aReagents and conditions: borane reagent (4 mmol), diphenylacetylene
(2 mmol),THF (2 M), unless noted otherwise. bIsolated yields. cReaction
performed under nitrogen. dReaction performed at 1 M. e56% 7a isolated.
f6 equiv reagent used. g32% 7a isolated. h65% 7a isolated.
1. (a) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents,
Academic Press, San Diego, CA, 1988. (b) Brown, H. C.;
Zaidlewicz, M. Organic synthesis via boranes, vol. 2, recent
developments. Aldrich, Milwaukee, 2001.
2. Transition metal-catalyzed diboration and dihydroboration is also
known: (a) Ramırez, R.; Segarra, A. M.; Fernández, E.
Reagents 1 and 2 gave yields lower than 3, with the isolation
of 6a in 71% each (Table 3, entries 2 and 3).16 The increased
yields of diol from using 2, as compared to those reported in the
literature,4,5,6 might be due to the effect of temperature and
stoichiometry on the product distribution. Generation of B2H6 in
situ from sodium borohydride and iodine17 in THF gave only
57% yield of 6a after isolation (Table 3, Entry 4), possibly due to
the loss of gaseous B2H6 at elevated temperatures. This prompted
us to consider the in situ generation of 3 from sodium
borohydride and ammonium sulfate in THF.11a To our delight, the
reaction proceeded akin to pre-synthesized 3, with the isolation
of 6a in 83% yield (Table 3, Entry 5) (Scheme 2).
́
Tetrahedron: Asymmetry, 2005, 16, 1289. (b) Lee, Y.; Jang, H.;
Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 18234. (c) Jung, H-.
Y.; Yun, J. Org. Lett. 2012, 14, 2606. (d) Semba, K.; Fujihara, T.;
Terao, J.; Tsuji, Y. Tetrahedron 2015, 71, 2183.
3.
Reaction of dihaloboranes with alkynes as a process for the
preparation of vinylboronic acids and esters is known, see Ref 1.
4. Brown, H. C.; Zweifel, G. J. Am. Chem. Soc., 1961, 83, 3834.
5. Hassner, A.; Braun, B. H. J. Org. Chem., 1963, 28, 261.
6. Pasto, D. J. J. Am. Chem. Soc., 1964, 86, 3039.
7. Reasoned to occur via the formation of a boron “ate” complex
with hydroxide, followed by extrusion of a carbanion, which is
immediately quenched, see Ref 4.
8. The former was presumed to be formed via vicinal
dihydroboration and the latter from geminal dihydroboration,
followed by hydrolytic cleavage. See Ref 5.
9. (a) Narasimhan, S.; Swarnalakshmi, S.; Balakumar, R. Indian J.
Chem. 1998, 37B, 1189. (b) Periasamy, M.; Thirumalaikumar, M.
J. Organomet. Chem. 2000, 609, 137. (c) Bambuch, V.; Otmar,
M.; Pohl, R.; Masojídková, M.; Holý, A. Tetrahedron, 2007, 63,
1589.
10. (a) Prokofjevs, A.; Boussonnière, A.; Li, L.; Bonin, H.; Lacôte, E.;
Curran, D. P.; Vedejs, E. J. Am. Chem. Soc., 2012, 134, 12281. (b)
McFadden, T. R.; Fang, C.; Geib, S. J.; Merling, E.; Liu, P.;
Curran, D. P. J. Am. Chem. Soc., 2017, 139, 1726.
Scheme 2. One-flask hydroboration of diphenylacetylene with
NaBH4/(NH4)2SO4.
11. (a) Ramachandran, P. V.; Gagare, P. D. Inorg. Chem. 2007, 46,
7810. (b) Ramachandran, P. V.; Gagare, P. D.; Sakavuyi, K.;
Clark, P. Tetrahedron Lett. 2010, 51, 3167. (c) Ramachandran, P.
V.; Raju, B. C.; Gagare, P. D. Org. Lett. 2012, 14, 6119. (d)
Ramachandran, P. V.; Kulkarni, A. S.; Pfeil, M. A.; Dennis, J. D.;
Willits, J. D.; Heister, S. D.; Son, S. F.; Pourpoint, T. L. Chem.
Eur. J. 2014, 20, 16869. (e) Ramachandran, P. V.; Kulkarni, A. S.
Inorg. Chem. 2015, 54, 5618. (f) Ramachandran, P. V.; Kulkarni,
A. S.; Zhao, Y.; Mei, J. G. Chem. Commun. 2016, 52, 11885.
12. Ramachandran, P.V.; Drolet, M. P.; Kulkarni, A. S. Chem.
Commun. 2016, 52, 11897.
13. For the synthesis, application, and resolution of 1,2-diols, see: (a)
Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.,
1994, 94, 2483. (b) Bhowmick, K. C.; Joshi, N. N. Tetrahedron:
Asymmetry 2006, 17, 1901. (c) Yıldız, T.; Yusufoğlu, A. Monatsh.
Chem. 2013, 144, 183. (d) Li, L.-J.; Zhang, Y.-Q.; Zhang, Y.; Zhu,
A.-L.; Zhang, G.-S. Chin. Chem. Lett., 2014, 25, 1161. (e) Patti,
A. Green Approaches To Asymmetric Catalytic Synthesis,
Dicyclohexylborane (8), which has been used extensively to
prepare ketones from internal alkynes,1 was examined next.
When 2 equivalents of this sterically hindered reagent were
heated at reflux in THF with 4a for 2 h, surprisingly, 42% of 6a
was isolated along with 56% yield of monoalcohol 7a (Table 3,
Entry 6). Utilizing an equivalency of available hydride analogous
to 1 (6 equiv 8) increased the yield of 6a to 62%, although at
great loss to atom economy. A representative alkylamine-borane,
tert-butylamine-borane (9) was subjected to these conditions to
examine the effect of substituted amine-boranes on alkyne
hydroboration. While only 12% yield of 6a was isolated, we were
surprised to discover that the bulky amine-borane reacted to form
monoalcohol 7a in 65% isolated yield. Future investigation will
include the reaction between alkylamine-boranes and alkynes,
particularly chiral amine-boranes.

4
Tetrahedron
Springer, Dordrecht, 2011. (f) Seemayer, R.; Schneider, M. P.;
J. Chem. Soc., Chem. Commun. 1991, 49.
14. See ESI for details.
15. This effect has been explored in detail for substituted styrenes.
Hydroboration/oxidation of styrenes and aliphatic alkenes bearing
an electron-withdrawing group formed a larger amount of internal
alcohols as compared to unsubstituted styrene, while aliphatic
alkenes and electron-rich styrenes predominantly formed terminal
alcohols. Brown, H. C.; Chen, G.-M.; Jennings, M. P.;
Ramachandran, P. V. Angew. Chem., Int. Ed. 1999, 38, 2052.
16. Surprisingly, extension of this methodology with BMS to other
aryl alkynes resulted in considerably lower yields of the 1,2-diol.
17. Prasad, A. S. B.; Kanth, J. V. B.; Periasamy, M. Tetrahedron
1992, 48, 4623.
18. (a) Ramachandran, P. V.; Kulkarni, A. S. Int. J. Hydrogen Energy
2017, 42, 1451. (b) Ramachandran, P. V.; Kulkarni, A. S. Dalton
Trans. 2016, 45, 16433.
Supplementary Material
Electronic Supplementary Information (ESI) available: See
DOI: 10.1039/x0xx00000x

5
•
1,2-Dihydroboration of aromatic alkynes
with ammonia borane is described
Hydroborations was performed under
completely open-flask conditions
Direct, uncatalyzed, synthesis of racemic
vicinal diols from alkynes is achieved
Use of In situ generated ammonia borane
gave the best yield for ( )-hydrobenzoin
•
•
•