Kinetic versus thermodynamic stereoselectivity in the hydrostannylation of propargylic alcohol derivatives using AIBN and Et3B as promotors

Article abstract of DOI:10.1002/chem.201202099

Et₃B versus AIBN: Equally radical? The stereoselectivity of hydrostannylation of internal propargyl alcohol derivatives has been studied by using both 2-2′-azobisisobutyronitrile (AIBN) and Et₃B as promoters. With silyl-protected alc

Full text of DOI:10.1002/chem.201202099

COMMUNICATION
DOI: 10.1002/chem.201202099
Kinetic versus Thermodynamic Stereoselectivity in the Hydrostannylation of
Propargylic Alcohol Derivatives Using AIBN and Et3B as Promotors**
Martins S. Oderinde, Howard N. Hunter, and Michael G. Organ*[a]
Vinylstannanes are highly versatile motifs that have been
employed in a wide variety of important synthetic transfor-
mations including transmetalation, tin–halogen exchange,
and cross-coupling reactions.[1] Consequently, the develop-
ment of methods for their efficient and selective preparation
has been pursued aggressively for decades.[2] The hydrostan-
nylation of alkynes is perhaps the most direct method to
generate vinylstannanes.[3] Very high levels of regioselectivi-
ty in tin hydride delivery have been attained with terminal
Scheme 1. Hydrostannylation of various internal alkynes using AIBN.
alkynes using both radical-mediated and metal-catalyzed ap-
proaches.[4] For internal alkynes, regioselectivity is far less
predictable as the ends of the alkyne are not as sterically
and/or electronically differentiated. That said, advancements
have been made with internal propargylic alcohols where it
has been proposed that the oxygen atom coordinates the in-
coming group under radical [nBu3SnH/AIBN],[5] palladium-
catalyzed [nBu3SnH/Pd0],[6] and copper-mediated
ethers are of limited synthetic utility, silyl ethers are the pre-
ferred protecting group of alcohols owing to their ease of in-
stallation and removal and the wide range of steric influence
that the ligands on silicon can exert on a variety of synthetic
transformations. Herein we report on the stereoselectivity,
[Bu3Sn(R)CuCNLi2][7] conditions (AIBN=2-2’-
azobisisobutyronitrile).
Table 1. Et3B-promoted nBu3SnH addition to compound 1.[a]
Since metal hydrides generally add syn to al-
kynes to provide E-olefins,[8] the free-radical hy-
drostannylation of alkynes is a rare method of
adding a metal hydride anti to alkynes to provide
Z-olefins. The major synthetic drawback of free-
radical hydrostannylation of internal alkynes is its
limitation to propargylic alcohols, or methyl ethers,
in order to achieve even reasonable regio- and ste-
reocontrol.[9] Both AIBN and Et3B have been used
as hydrostannylation catalysts to achieve Z-olefins
from internal alkynes. Whereas Et3B is generally
used at 238C and below (as low as À788C), AIBN
is typically used at 708C and above (as high as
2008C). Although regiocontrol is generally good in
the hydrostannylation of propargylic silylethers,
acetates, and homopropargylic alcohols using
nBu3SnH/AIBN, predictable stereocontrol has re-
mained elusive (Scheme 1).[9] Whereas methyl
Entry
nBu3SnH
[equiv]
Additive
T
[8C]
80[d]
23
23
t
2Z/2E[b]
(Yield [%])[c]
G
[h]
ACHTUNGTRENNUNG
1
2
3
4
5
6
7
8
2
2
2
5
5
2
2.5
2
AIBN
Et3B
Et3B
Et3B
Et3B plus air
Et3B plus air
Et3B plus air
AIBN plus Et3B plus air
3
24
48
48
48
3
55:45 (98)
>99:1[e] (30)
>99:1 (60)
>99:1 (85)
>99:1 (98)
>99:1 (95)
>99:1 (99)
55:45 (yield ND)
23
23
80[d]
80[d]
80[d]
3
3
[a] Reactions performed with Et3B in toluene required more time to complete. [b] Iso-
meric ratio was determined by 1H NMR spectroscopy of the crude reaction mixture.
[c] Yield was determined after purification by silica gel chromatography. [d] Refers to
the temperature setting of the oil bath. [e] A reported >99:1 ratio means that the
minor isomer is not observed at all.
isomerization, and mechanism of hydrostannylation of inter-
nal propargylic alcohol derivatives using Et3B and AIBN as
promoters.
[a] M. S. Oderinde, Dr. H. N. Hunter, Prof. M. G. Organ
Department of Chemistry, York University
4700 Keele Street, Toronto, ON, M3J 1P3 (Canada)
Fax : (+1)416-736-5936
Stereoselectivity studies: Under the conditions necessary to
activate AIBN (i.e., 808C, Table 1, entry 1), little stereose-
lectivity could be achieved using it.[10] Solvent screening re-
vealed that there was no benefit afforded by the use of coor-
dinating solvents, as has been observed in other hydrometal-
E-mail: organ@yorku.ca
[**] AIBN=2-2’-azobisisobutyronitrile.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202099.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

lation procedures.[11] Triethylborane (Et3B) has also been
used as a promoter for hydrostannylation[12] and reported to
proceed by the same radical-propagating mechanism as
AIBN.[13] Hale reported the room-temperature hydrostanny-
lation of propargyl alcohols and acetals with Ph3SnH using
catalytic Et3B as the radical promoter, inspiring us to try
it.[14] When the hydrostannylation of 1 was carried out at
room temperature using nBu3SnH/Et3B in benzene, the Z
isomer was attained selectively, albeit in low yield (Table 1,
entry 2). Increasing the time (entry 3) and equivalents of
stannyl hydride (entry 4) steadily increased conversion while
maintaining selectivity. Running the reaction in air (entry 5),
which would provide more oxygen that is necessary for radi-
cal initiation,[15] led to complete conversion to 2Z. Presum-
ing that the Z isomer is the kinetic product, we wondered if
the high selectivity was attributable to the cooler tempera-
ture.[16] To this end, the reaction was carried out at 808C
(entry 6) and, strikingly, after 3 h no E isomer was detected.
Thus, the observed stereoselectivity in the Et3B/air/benzene
system is not the result of temperature, but rather is a conse-
quence of the involvement of Et3B. Whereas the hydrostan-
nylation of 1 in the presence of AIBN was non-stereoselec-
tive, absolute selectivity was obtained with Et3B. However,
when AIBN and Et3B were used together (entry 8) AIBN
effects dominate, which is likely a consequence of isomeriza-
tion.
Table 2. Comparative scope studies for AIBN- and Et3B-promoted hy-
drostannylation.[a,b]
To probe the generality of the nBu3SnH/Et3B/air condi-
tions, we embarked on a scope study that included direct
comparisons with AIBN as the promoter (Table 2). It ap-
pears as though the selectivity seen with nBu3SnH translates
equally well to Ph3SnH (e.g., 4, 12, 14). Interestingly, where-
as the reactions with Et3B appear to tolerate all substituents
on the propargylic alcohol (e.g., TBS: 4, OAc: 5, TIPS: 6;
TBS=tert-butylsilyl, TIPS=triisopropylsilyl), all TIPS-con-
taining substrates that were attempted with AIBN failed to
react (i.e., 6, 13, 14). We explored polyol derivatives, not
only for their widespread synthetic utility, but to see how
such closely positioned functionality affects regio- and ster-
eochemistry.[9,14a] AIBN-mediated reactions proceeded with
marginal, if any stereoselectivity (5, 7, 8, 9, 10, 11, 15, 16,
17), whereas all examples using Et3B/air were fully selective.
To probe the effect that alcohol protection has on the se-
lectivity of this transformation, we examined free-alcohol 18
(Scheme 2). Whereas the Et3B/air system gave a mixture of
regioisomers (Scheme 2, [Eq. (1)]), AIBN led exclusively to
regioisomer 19 (Scheme 2,
[a] Isomeric ratio was determined by 1H NMR spectroscopy of the crude
reaction mixture. [b] Yield was determined after purification by silica gel
chromatography. Reaction conditions: [c] Alkyne (0.5m in benzene),
Et3B (10 mol%), nBu3SnH (2 equiv), oil bath set to 808C. [d] Alkyne
(0.5m in benzene), AIBN (10 mol%), nBu3SnH (2 equiv), oil bath set to
808C. [e] Alkyne (0.5m in benzene), Et3B (10 mol%), Ph3SnH (2 equiv),
238C. [f] Alkyne (0.5m in benzene), Et3B (1 equiv), nBu3SnH (2 equiv),
oil bath set to 808C. [g] Alkyne (0.5m in benzene), Et3B (1 equiv),
Ph3SnH (2 equiv), 238C.
pure 2Z and submitted it to the reaction conditions with
both promoters (Scheme 3, [Eq. (1)]). Under AIBN condi-
tions significant isomerization was observed, whereas none
[Eq. (2)]). However, whereas
AIBN provided a mixture of
stereoisomers (Z/E 90:10),
only single stereoisomers (i.e.,
Z) of 19 and 20 were produced
with Et3B.
Isomerization studies: To con-
firm that the AIBN conditions
lead to isomerization, whereas
Et3B/air does not, we prepared
Scheme 2. Hydrostannylation of 18 promoted by AIBN and Et3B.
&
2
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Stereoselectivity in the Hydrostannylations
COMMUNICATION
firms that the species that ac-
tually drives the addition to
the alkyne remains present, at
some level. In addition, while
only
1–1.1 equivalents
of
nBu3SnH is required for hy-
drostannylation with AIBN,
2 equivalents is required with
Et3B.
Taken together, the rate
(Figure 1) and isomerization
Scheme 3. Isomerization studies of 2Z and 2E using AIBN and Et3B.
studies (Scheme 3) illustrate
that the operational mecha-
was observed with Et3B/air after 3 h. Isomer 2E appears to
be a thermodynamic sink as the same control experiments
(Scheme 3, [Eq. (2)]) resulted in no visible isomerization
with either promoter. The presence of the propargylic
oxygen, and whether it is substituted or not, has a significant
impact on the hydrostannylation results in this study with
both promoter systems.
nism under Et3B/air conditions does not allow the vinylstan-
nane product to isomerize meaning that addition is under
strict kinetic control. To ensure that the lack of isomeriza-
tion with Et3B was not simply a consequence of depleted
Et3B we added excess of it to the isomerization of 2Z in
three portions of 0.1 equiv each over 30 min. (every 10 min)
at 808C and still no isomerization occurred. At the same
time we followed the rate of AIBN-mediated isomerization
of 2Z and discovered that isomerization is in fact quite
Mechanistic studies: The striking differences in stereoselec-
tivity between the AIBN and Et3B experiments in this
study, conducted under near identical conditions, caused us
to reconsider the currently accepted mechanism of Et3B-
mediated tin hydride addition.[12–14] Perhaps it is not the
identical propagating radical process as is the case with
AIBN? The rate of AIBN degradation into isobutyronitrile
radical in solvents such as toluene[17] is considerably slower
than the autoxidation of Et3B in the presence of oxygen.[18]
We have not seen hydrostannylation studies that have care-
fully followed the rates of isomerization using AIBN, rather
the extent of isomerization over the course of some number
of hours is usually reported. This could give the impression
that AIBN isomerizes the vinylstannane products from Z to
E slowly but progressively over time as fresh radical is intro-
duced gradually into the reaction mixture (i.e., hours). Con-
versely, the faster autoxidation of Et3B would deplete more
rapidly the source of any short-lived radicals under the con-
ditions in this manuscript (808C in air). To examine this we
monitored the rate of the hydrostannylation of 1 under iden-
tical reaction conditions with AIBN and Et3B (Figure 1).
Not only do the reactions proceed at noticeably different
rates, surprisingly, AIBN proceeded considerably faster.
While the Et3B-promoted reaction takes 90 min. to reach
80% completion, AIBN leads to the same level of comple-
tion after just 10 min. Following the generally accepted
mechanism, one might expect not only the opposite trend in
relative rates for these promoters, but that the rate with
Et3B would be much more rapid, that is, to complete within
minutes or less. Indeed the radical decomposition of Et3B
by oxygen is so exothermic that the exposure of neat Et3B
to air leads to its immediate ignition. It is interesting that so
much radical, presumably, could be released during the ini-
tial seconds of this reaction with Et3B,[18,19] yet it takes so
long to complete. However, that it does continue to hydro-
stannylate beyond 90 min until it reaches completion con-
Figure 1. Rate of hydrostannylation of 1 using a) AIBN and b) Et3B.
Both reactions were run under air. The AIBN reaction done under argon
proceeded at the identical rate.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

M. G. Organ et al.
[4] a) N. D. Smith, J. Mancuso, M. Lautens, Chem. Rev. 2000, 100, 3257;
b) C. Rꢁchardt, Angew. Chem. 1970, 82, 845; Angew. Chem. Int. Ed.
Engl. 1970, 9, 830.
[5] W. P. Neumann, The Organic Chemistry of Tin, Wiley, New York,
1970.
[6] a) B. M. Trost, Z. T. Ball, Synthesis 2005, 6, 853; b) M. Lautens, J.
Mancuso, Org. Lett. 2000, 2, 671; c) J. A. Marshall, B. M. Bourbeau,
Tetrahedron Lett. 2003, 44, 1087.
rapid. The equilibrium shown in Scheme 3, Equation (1) is
reached in just 30 min and 20% isomerization has taken
place after just 10 min. Thus, if the same radical-propagation
mechanism during hydrometallation was operating with
Et3B/air, there is ample promoter and enough time to equili-
brate 2Z, yet it does not.
In conclusion, this comparative hydrostannylation study
of Et3B and AIBN at 808C has revealed that there are clear
differences in the mechanisms by which these promoters
affect tin hydride addition to alkynes. The Et3B/air system
promoted tin-hydride addition under very mild conditions
(RT) with complete preference for the Z vinylstannane. Fur-
ther, these conditions are fully regioselective to place the tin
moiety on the alkyne carbon proximal to the oxygen sub-
stituent. In all cases employing AIBN, approximately 50/50
mixtures of Z and E isomers were obtained. Investigations
into what makes the Et3B pathway distinct from AIBN are
under way in our laboratories.
[7] a) B. M. Stoltz, T. Kano, E. J. Corey, J. Am. Chem. Soc. 2000, 122,
9044; b) J. F. Betzer, F. Delaloge, B. Muller, A. Pancrazi, J. Prunet,
J. Org. Chem. 1997, 62, 7768; c) E. Piers, J. M. Chong, H. Morton,
Tetrahedron Lett. 1981, 22, 4905.
[8] a) C. F. Thompson, T. F. Jamison, E. N. Jacobsen, J. Am. Chem. Soc.
2000, 122, 10482; b) E.-i. Negishi, L. D. Boardman, H. Sawada, V.
Bagher, T. A. Stoll, J. M. Tour, C. L. Rand, J. Am. Chem. Soc. 1988,
110, 5383; c) Reviews: S. R. Chemler, D. Trauner, S. J. Danishefsky,
Angew. Chem. 2001, 113, 4676; Angew. Chem. Int. Ed. 2001, 40,
4544; d) K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem.
2005, 117, 4516; Angew. Chem. Int. Ed. 2005, 44, 4442.
[9] M. Taddei, C. Nativi, J. Org. Chem. 1988, 53, 820.
[10] The ratio of isomers in this study was carefully determined by
1H NMR spectroscopy on well-separated resonances with excellent
signal-to-noise ratios. For examples of spectra and analyses, see the
Supporting Information.
[11] a) K. Akiyama, F. Gao, A. H. Hoveyda, Angew. Chem. 2010, 122,
429; Angew. Chem. Int. Ed. 2010, 49, 419; b) T. L. May, J. A. Dab-
rowski, A. H. Hoveyda, J. Am. Chem. Soc. 2011, 133, 736. For exam-
ples from the current study, see Table S1 in the Supporting Informa-
tion.
[12] K. Nozaki, K. Oshima, K. Utimoto, Tetrahedron 1989, 45, 923.
[13] K. Nozaki, K. Oshima, K. Utimoto, J. Am. Chem. Soc. 1987, 109,
2547.
Acknowledgements
This work was supported by NSERC (Canada) and The Ontario Re-
search Fund (ORF) (Ontario).
[14] a) P. Dimopoulos, J. George, D. A. Tocher, S. Manaviazar, K. Hale,
Org. Lett. 2005, 7, 5377; b) P. Dimopoulos, A. Athlan, S. Manavia-
zar, J. George, M. Walters, L. Lazarides, A. E. Aliev, K. Hale, Org.
Lett. 2005, 7, 5369.
Keywords: 2-2’-azobisisobutyronitrile · hydrostannylation ·
radicals · stereoselectivity · triethylborane
[15] P. Renaud, A. Beauseigneur, A. Brecht-Forster, B. Becattini, V. Dar-
mency, S. Kandhasamy, F. Montermini, C. Ollivier, P. Panchaud, D.
Pozzi, E. M. Scanlan, A.-P. Schaffner, V. Weber, Pure Appl. Chem.
2007, 79, 223.
[16] C. Ollivier, P. Renaud, Chem. Rev. 2001, 101, 3415, and the referen-
ces therein.
[1] a) D. Milstein, J. K. Stifle, J. Am. Chem. Soc. 1979, 101, 4992; b) D.
Milstein, J. K. Stifle, J. Am. Chem. Soc. 1978, 100, 3636; c) D. A.
Evans, W. C. Black, J. Am. Chem. Soc. 1993, 115, 4497; d) J. R. Beh-
ling, K. A. Babiak, J. S. Ng, A. L. Campbell, R. Moretti, M. Koerner,
B. H. Lipshutz, J. Am. Chem. Soc. 1988, 110, 2641.
[2] a) D. Hart, Science 1984, 223, 883; b) B. Giese, Angew. Chem. 1985,
97, 555; Angew. Chem. Int. Ed. Engl. 1985, 24, 553; c) K. W. Kells,
J. M. Chong, J. Am. Chem. Soc. 2004, 126, 15666; d) K. W. Kells,
J. M. Chong, Org. Lett. 2003, 5, 4215; e) E. J. Panek, L. R. Kaiser,
G. M. Whitesides, J. Am. Chem. Soc. 1977, 99, 3708.
[3] a) D. Seyferth, F. G. A. Stone, J. Am. Chem. Soc. 1957, 79, 515;
b) J. W. Labadie, J. K. Stille, J. Am. Chem. Soc. 1983, 105, 6129; c) S.
Matsubara, J.-I. Hibino, Y. Morizawa, K. Oshima, H. Nozaki, J. Or-
ganomet. Chem. 1985, 285, 163; d) E.-i. Negishi, Organometallics in
Organic Synthesis, Wiley, New York, 1980; 410.
[17] J. W. Timberlake, J. C. Martin, The Review of Scientific Instruments
1973, 44, 151.
[18] I. U. Ingold, J. Chem. Soc. Chem. Commun. 1969, 911.
[19] We followed the fate of Et3B under air and under argon by
11B NMR spectroscopy; see: M. S. Oderinde, H. N. Hunter, R. D. J.
Froese, M. G. Organ, Chem. Eur. J. 2012, DOI: 10.1002/
chem.201202100. For related work, see: Z.-C. Zhang, M. Chung,
Macromolecules 2006, 39, 5187.
Received: June 13, 2012
Published online: && &&, 0000
&
4
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Stereoselectivity in the Hydrostannylations
COMMUNICATION
Reaction Mechanisms
M. S. Oderinde, H. N. Hunter,
M. G. Organ* ................. &&&& — &&&&
Kinetic versus Thermodynamic Stereo-
selectivity in the Hydrostannylation of
Propargylic Alcohol Derivatives Using
AIBN and Et3B as Promotors
Et3B versus AIBN: Equally radical?
The stereoselectivity of hydrostannyla-
tion of internal propargyl alcohol
derivatives has been studied by using
both 2-2’-azobisisobutyronitrile
(AIBN) and Et3B as promoters. With
silyl-protected alcohols, complete Z
selectivity of the resultant vinylstan-
nane has been achieved with Et3B,
whereas AIBN shows zero stereoselec-
tivity. Evidence suggests that, despite
decades of acceptance, the hydrostan-
nylation mechanisms employing Et3B
and AIBN appear to be mechanisti-
cally distinct.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!