A one-pot allylation-hydrostannation sequence with recycling of the intermediate tin waste

Article abstract of DOI:10.1021/ol500460u

A one-pot allylation and hydrostannation of alkynals where the tin byproduct formed in the first step of the reaction is recycled and used in the second step of the sequence is presented. Specifically, a BF₃· OEt₂-promoted allylstannation of the aldehyde moiety in the alkynal is followed by the introduction of polymethylhydrosiloxane (PMHS) and catalytic B(C₆F₅)₃, which convert the tin byproduct of the allylation into Bu₃SnH, which then hydrostannates the alkyne in the molecule. ¹¹⁹Sn and ¹¹B NMR data suggest an organotin fluoride species is formed during the allylation step and involved in the tin recycling step.

Full text of DOI:10.1021/ol500460u

Letter
pubs.acs.org/OrgLett
A One-Pot Allylation−Hydrostannation Sequence with Recycling of
the Intermediate Tin Waste
Banibrata Ghosh, Maria Del Rosario I. Amado-Sierra, Daniel Holmes, and Robert E. Maleczka, Jr.*
Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, Michigan 48824, United States
S
* Supporting Information
ABSTRACT: A one-pot allylation and hydrostannation of alkynals
where the tin byproduct formed in the first step of the reaction is
recycled and used in the second step of the sequence is presented.
Specifically, a BF3·OEt2-promoted allylstannation of the aldehyde
moiety in the alkynal is followed by the introduction of
polymethylhydrosiloxane (PMHS) and catalytic B(C6F5)3, which
convert the tin byproduct of the allylation into Bu3SnH, which then
hydrostannates the alkyne in the molecule. 119Sn and 11B NMR data
suggest an organotin fluoride species is formed during the allylation
step and involved in the tin recycling step.
reviously, we reported in situ reductions of organotin
halides and oxides by PMHS to afford organotin hydrides
choice of reducing agents either of these tin intermediates/
byproducts could be reduced in situ to Bu3SnH.15
P
that can be employed in various hydrostannation protocols,
including one-pot hydrostannation/Stille sequences catalytic in
tin.1 These successes drove us to consider other one-pot
processes where the tin byproducts of an early step could be
recycled and used in subsequent chemistry. We identified
allylations as a reaction type that lends itself to such a one-pot
sequence.
Allylation reactions of allylstannanes and aldehydes can take
place under thermal,2 high pressure,3 Lewis acidic,4 or
transition-metal-catalyzed5 conditions. The homoallylic alcohol
products of such reactions can be converted to β-
hydroxyaldehydes,6 δ-lactones,7 epoxides, or other oxygen-
bearing compounds.8 They can also be used in ring-closing
metathesis9 and cross-coupling reactions.10
An application of allylation chemistry that caught our
attention was Nicolaou and co-workers’11 syntheses of
palmerolide A analogues where an aldehyde allylation was
followed by an alkyne hydrostannation. This report prompted
us to consider development of an allylation−hydrostannation
protocol where the tin waste of the allylation step would be
converted to an organotin hydride that would then be used in
an ensuing hydrostannation reaction. Such a combined process
would minimize tin handling and reduce the overall amount of
tin reagents employed in syntheses as compared to these two
steps performed separately.12,13
To develop the proposed allylation−hydrostannation proto-
col, knowledge of the nature of the tin byproducts of the
allylation step is essential. Toward this end, Yamamoto and co-
workers reported that palladium (or platinum)-catalyzed
condensation of allylstannanes with aldehydes proceeds via
intermediacy of stannyl ethers.5 On the other hand, Baba and
co-workers documented that allylations of aldehydes with
allyltributylstannane and a catalytic amount of Bu2SnCl2 afford
Bu3SnCl as a waste product.14 We anticipated that with proper
In practice, though, neither of these methods proved
amenable to one-pot allylation−hydrostannation performed
with 1, 2a, and 3. In such cases, the allylation of 1 went
smoothly, resulting in 4 (Yamamoto’s protocol) or the benzoyl
derivative of 4 (Baba’s protocol); however, in situ organotin
hydride formation and subsequent hydrostannation of 3 by the
action of PMHS, PMHS/TBAF, or Et3SiH as the reducing
agent with Pd or Pt as the hydrostannation catalyst failed.
Given the incompatibility of the Yamamoto/Baba methods
with our one-pot concept, we explored BF3·OEt2-mediated
allylations,16 even though the tin intermediates that form in
these reactions are not well characterized.17a−e In addition to
the uncertain nature of the tin byproducts, we recognized that
developing a one-pot allylation−hydrostannation sequence
would be hampered by the inability of common hydro-
15b
stannation catalysts, e.g., PdCl2(PPh3)2
or MoBI3,18 to
survive in the presence of BF3·OEt2. Rather than fighting
against the Lewis acidic nature of BF3·OEt2, we decided to
exploit it by employing a Lewis acid mediated hydrostannation
in the second step of our proposed sequence. Thus, B(C6F5)3
was chosen as the hydrostannation catalyst.15a,19 Et3SiH was
initially used as the hydride source per Yamamoto’s in situ
generation of Bu3SnH for B(C6F5)3-catalyzed hydrostannation-
s.15a
Gratifyingly, with 10 mol % of B(C6F5)3 and 1 equiv of
Et3SiH as the reducing agent, formation of 56% homoallylic
alcohol 4 and 32% z-vinylstannane 5 was observed in the
reaction using DCM as solvent (Table 1, entry 1). After
significant optimization, we determined that 1.05 equiv of BF3·
OEt2 in conjunction with 20 mol % of B(C6F5)3 and 2 equiv of
Received: February 12, 2014
Published: April 11, 2014
© 2014 American Chemical Society
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Letter
Table 1. Optimization of One-Pot Allylation−Hydrostannation Sequence
b
c
c
entry
BF3·OEt2 (equiv)
solvent
temp (°C)
B(C6F5)3 (mol %)
reductant (equiv)
yield 4 (%)
yield 5 (%)
1
2
DCM
0
0
10
20
20
100
20
0
A (1)
56
60
72
12
63
71
46
62
75
71
38
73
61
74
78
32
55
65
0
2
2
DCM
A (1)
3
2
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
0
A (1)
4
2
0
A (1)
5
2
0
A (1.5)
85
8
6
2
0
A (1.5)
7
2
0
20
30
20
20
20
20
20
20
20
A (2)
76
35
62
86
52
92
99
93
100
8
2
0
A (1.5)
9
2
0
B (1) + C (cat.)
B (2) + C (cat.)
B (3) + C (cat.)
B (2) + C (cat.)
B (2)
10
11
12
13
2
0
2
0
2
−35
−35
−35
−35
3
a
14
1.05
1.05
B (2)
a
15
B (2)
a
b
Entries 1−14 were quenched with 2.2 equiv of Et3N, and entry 15 was quenched with 1.4 equiv of Et3N. A = Et3SiH, B = PMHS, C = TBAF.
Determined using Me3SiOSiMe3 as internal standard.
c
PMHS in toluene at −35 °C followed by quenching the
reaction with 1.4 equiv of NEt3 furnished the highest combined
yield of homoallylic alcohol 4 (78%) and vinylstannane 5
(100%) (Table 1). Compound 4 and 5 were isolated in 71%
and 99% yield, respectively. Curiously, the hydrostannation
result appears to stand in contrast with Yamamoto and co-
workers’ finding that reactions of B(C6F5)3 tend to be inhibited
by the presence of PMHS.15a
Having achieved a one-pot allylation−hydrostannation
protocol where the aldehyde and alkyne moieties were separate,
we sought to demonstrate the effectiveness of this protocol on
alkynals 6−13 (Table 2). Aromatic alkynals 7, 8, 10, and 11
were synthesized from commercially available bromo- or iodo-
substituted aromatic aldehydes via Sonogashira coupling with
TMS-acetylene followed by K2CO3 desilylation.20 Aliphatic
alkynals 12 and 13 were synthesized from the corresponding
alkynols via Swern oxidation.20
Most of these alkynals responded favorably to the reaction
conditions, producing allylation−hydrostannation products in
the same reaction pot in fair yields (Table 2). Even though the
allylation step of the reaction was fast for all the substrates
examined (15−60 min except for entry 9), both sterics and
electronics governed the fate of the hydrostannation step.
While hydrostannation of 4-ethynylbenzaldehyde (6) was the
fastest (1 h) (Table 2, entry 1), the same reaction became
increasingly slower when the ethynyl group moved closer to the
aldehyde moiety (14 h for 7 and 1 d for 9). An electron-
withdrawing group was tolerated in the reaction (entry 3),
albeit requiring a 3 d hydrostannation time. The presence of an
electron-donating group inhibited the hydrostannation step
(entry 5) as did an o-methyl (entry 6). For aliphatic alkynals
(12 and 13), the second step of the reaction was the slowest (3
d) and yields were lower compared to most of their aromatic
counterparts that successfully underwent allylation−hydro-
stannation. Finally, crotylation of 6 with (E)-crotylstannane
(2b) (entry 9) was slower than the allylation (1.5 h vs 15 min).
In all cases, (Z)-vinylstannanes were the exclusive or
predominant product as reported earlier.19
To account for the moderate final product yields in the one-
pot reactions and to compare their efficiency against a stepwise
protocol, we carried out allylation and hydrostannation of an
alkynal in two separate steps. The allylation product from
reaction of 4-ethynylbenzaldehyde (6) and allylstannane (2a)
in the presence of BF3·OEt2 was purified and subjected to
B(C6F5)3-catalyzed hydrostannation with freshly prepared
Bu3SnH without PMHS. The yield of the hydrostannation
product eroded (35%) in the stepwise protocol, and a 1.4/1
mixture of (Z)- and (E)-stannanes was produced along with
46% of the starting alkynol.20 Notably, 71% of this alkynol was
recovered when exposed to 20 mol % of B(C6F5)3 and 2 equiv
of PMHS and only trace amounts of (Z)-stannane was
observed when freshly prepared Bu3SnH was added to this
mixture. These results indicate that degradation of the alkynol
under our conditions does not fully explain the moderate yields
of the final products. However, when allylation−hydro-
stannation product 14 was subjected to a reaction with 1
equiv of allylstannane (2a), 1.05 equiv of BF3·OEt2, 20 mol %
of B(C6F5)3, and 2 equiv of PMHS and the resulting mixture
was chromatographed, only 40% 14 was recovered along with
protiodestannylated material and other unidentified impurities.
This degradation of the final product in the reaction mixture is
consistent with the moderate yields of the allylation−hydro-
stannation products in our one-pot protocol.
In order to show a synthetic application of our one-pot
allylation−hydrostannation protocol, we treated compound 17
with I2 to afford the corresponding vinyl iodide 22. An
unoptimized Pd-catalyzed intramolecular Heck cyclization of
crude 22 afforded 23 in 35% yield over two steps (Scheme 1).
As stated earlier, the tin intermediates that form in BF3·OEt2
reactions of allyltributyltin and aldehydes have not been well
characterized.17a−e Denmark and co-workers have found direct
evidence for interaction between the Lewis acid and the allylic
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reaction mixture of the aldehyde and stannane showed only the
characteristic peak for allyltributylstannane (∼18 ppm).22
When BF3·OEt2 was added, a doublet at ∼156 ppm
(Intermediate I) (Figure 1) slowly grew in as the peak at
Table 2. One-Pot Allylation−Hydrostannation of Alkynals
Figure 1. Mechanistic rationale of one-pot allylation−hydrostannation
protocol.
∼18 ppm diminished. The chemical shift and large coupling
constant (J = 1550 Hz) observed for this doublet is consistent
with a Sn−F species.23 The 11B NMR spectrum of
Intermediate I showed peaks at 0.21 and −1.11 ppm, the
latter corresponding to a boryl ether. When B(C6F5)3 and
PMHS were added to this mixture, the doublet in the 119Sn
spectrum shifted to 165 ppm (J = 1538 Hz) and a new peak at
−88 ppm was visible corresponding to tributyltin hydride
(Intermediate mixture II).22 It should be noted that
Intermediates I and II may not be discrete complexes.
Organotin fluorides are rarely monomeric in solution, existing
instead as polymeric structures. The relatively broad 119Sn
NMR peaks observed for Intermediates I and II (150−250 Hz
line widths vs 5−20 Hz for the discrete vinyltins) suggest that
they too may exist as aggregates.
a
b
Yields shown are a two-run average. Allylation−hydrostannation
c
product was not observed. 90 min allylation reaction time, erythro/
threo =7/1 based on NMR of crude material; product degradation
occurred.
Scheme 1. Synthetic Application of One-Pot Allylation−
Hydrostannation
To confirm that the splitting of the peak at 165 ppm in the
119Sn NMR spectrum was due to fluorine, we performed a
fluorine-decoupled 119Sn NMR experiment of the mixture.
Selective 19F decoupling on the region around −194 ppm
resulted in a collapse of the doublet, thereby confirming that
stannane in the presence of the substrate aldehyde and that
boryl ethers were the sole products of the allylation reaction
and not stannyl ethers.17b To the best of our knowledge, there
are no reports on BF3·OEt2-mediated allylations being followed
by 119Sn and 11B NMR, although such studies have been
described for SnCl417f and solvent-mediated17g allylstannations.
In an attempt to provide at least some insight into the fate of
the tin in BF3·OEt2-mediated allylations and throughout our
own allylation−hydrostannation sequence, we monitored the
allylation−hydrostannation reaction of 1, 2a, and 3 by 119Sn
and 11B NMR.21 In the absence of BF3·OEt2, 119Sn NMR of the
the splitting was due to 19F scalar coupling.20 At this point, 11
B
NMR showed the presence of another boryl ether at −1.33
ppm. Finally, upon addition of phenylacetylene (3), the
tributyltin hydride and tin-doublet peaks disappeared and a
peak corresponding to vinylstannane 5 appeared at −56 ppm in
the 119Sn NMR spectrum. 11B NMR of the mixture revealed
resonances at 0.13 and −1.40 ppm, the latter being consistent
with presence of another boryl ether.
2320
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Organic Letters
Letter
1987, 20, 243−249. (c) Denmark, S. E.; Weber, E. J. J. Am. Chem. Soc.
1984, 106, 7970−7971.
Based on our NMR evidence, the following mechanistic
rationale is proposed: The aldehyde reacts with allylstannane in
the presence of BF3·OEt2 to form a boryl ether and the positive
(or partially positive) Sn−F intermediate.24 PMHS, activated
by B(C6F5)3,25 reduces this Sn−F intermediate into tributyltin
hydride. Tributyltin hydride then enters the B(C6F5)3 catalytic
cycle to produce the corresponding vinylstannanes.19 The
NMR data for the Sn−F species indicated that it is not Bu3SnF,
which appears as a triplet at δ −10 ppm with J = 1350 Hz in
hexane,26 or a Bu3SnF· B(C6F5)3 adduct, which appears at −18
ppm in toluene.20 To further eliminate the possibility of
Bu3SnF involvement, hydrostannation of phenylacetylene (3)
was performed with premade tributyltin fluoride (1 equiv),
B(C6F5)3 (20 mol %), and PMHS (2 equiv). (Z)- and (E)-
vinylstannanes were produced in almost equal amounts with a
combined yield of 11%. The unselective product formation and
low yield obtained further support the unlikelihood of Bu3SnF
being reduced to Bu3SnH in our one-pot protocol.
(5) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996,
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Organomet. Chem. 2001, 624, 383−387. (b) Toshima, K.; Arita, T.;
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L.; Fargeas, V.; Zammattio, F.; Quintard, J.-P.; Biesemans, M.; Willem,
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In summary, we have developed a one-pot allylation−
hydrostannation sequence of alkynals where tin waste from the
allylation step is successfully recycled for use in the hydro-
stannation reaction. The unique reagent mix of this one-pot
protocol selectively affords (Z)-stannanes unlike the E/Z
generating stepwise reaction protocol. The allylation−hydro-
stannation product of the reaction can be manipulated to more
complex molecules. Monitoring the reaction with 119Sn and 11
B
NMR revealed that a Sn−F intermediate is formed during the
BF3·OEt2-mediated reaction between the aldehyde and
allyltributylstannane. That Sn−F intermediate is reduced to
Bu3SnH by B(C6F5)3-activated PMHS. B(C6F5)3 also acts as a
catalyst for the subsequent hydrostannation.
(17) (a) Boaretto, A.; Morton, D.; Tagliavini, G.; Ganis, P. J.
Organomet. Chem. 1987, 321, 199−207. (b) Denmark, S. E.; Wilson,
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ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details and product characterization data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: Maleczka@chemistry.msu.edu.
Notes
The authors declare no competing financial interest.
(20) See the Supporting Information for details.
ACKNOWLEDGMENTS
■
(21) Monitoring these reactions using NMR proved to be
challenging. Thorough mixing, careful temperature control, and
accurate reagent addition were essential to success.20
(22) Davies, A. G. Organotin Chemistry, 2nd ed.; Wiley-VCH:
Weinheim, Germany, 2004.
We thank A. Daniel Jones and Lijun Chen of MSU’s Mass
Spectrometry Core for valuable discussions and technical
assistance. We also thank the National Science Foundation
(CHE-9984644) and the Astellas USA Foundation for funding.
(23) (a) Dakternieks, D.; Zhu, H. Organometallics 1992, 11, 3820−
3825. (b) Al-Juaid, S. S.; Dhaher, S. M.; Eaborn, C.; Hitchcock, P. B.;
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McDonald, R. J. Am. Chem. Soc. 2002, 124, 1295−1306.
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L. G. J. Phys. Chem. 1994, 98, 4919−4922.
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