Silver-catalyzed aldehyde olefination using siloxyalkynes

Article abstract of DOI:10.1002/adsc.200900835

We describe the development of a silvercatalyzed carbonyl olefination employing electronrich siloxyalkynes. This process constitutes an efficient synthesis of trisubstituted unsaturated esters, and represents an alternative to the widely utilized Horner-Wadsworth-Emmons reaction. Excellent diastereoselectivities are observed for a range of aldehydes using either 1-siloxy-l-propyne or 1-siloxy1-hexyne. This mild catalytic process also enables chemoselective olefination of aldehydes in the presence of either ester or ketone functionality. Furthermore, since no by-products are generated, this catalytic process is perfectly suited for development of sequential reactions that can be carried out in a single flask.

Full text of DOI:10.1002/adsc.200900835

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DOI: 10.1002/adsc.200900835
Silver-Catalyzed Aldehyde Olefination Using Siloxyalkynes
Jianwei Sun,a Valerie A. Keller,a S. Todd Meyer,a and Sergey A. Kozmina,*
a
Department of Chemistry, University of Chicago, 5735 S. Ellis Ave, Chicago, IL 60637, USA
Fax : (+1)-773-702-0805; phone: (+1)-773-702-6886; e-mail: skozmin@uchicago.edu
Received: November 30, 2009; Revised: January 31, 2010; Published online: March 9, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900835.
Abstract: We describe the development of a silver-
catalyzed carbonyl olefination employing electron-
rich siloxyalkynes. This process constitutes an effi-
cient synthesis of trisubstituted unsaturated esters,
and represents an alternative to the widely utilized
Horner–Wadsworth–Emmons reaction. Excellent
diastereoselectivities are observed for a range of al-
dehydes using either 1-siloxy-1-propyne or 1-siloxy-
1-hexyne. This mild catalytic process also enables
chemoselective olefination of aldehydes in the pres-
ence of either ester or ketone functionality. Further-
more, since no by-products are generated, this cata-
lytic process is perfectly suited for development of
sequential reactions that can be carried out in a
single flask.
Scheme 1. Alternative carbonyl olefination strategies.
Keywords: chemoselectivity; olefination; siloxyal-
kynes; silver
selective and diastereoselective Arens olefination,
which would proceed under mild conditions and dis-
play high catalytic turnover, has not been achieved.
Such a transformation would have significant poten-
tial for broad implementation in organic synthesis.
We recently identified AgNTf2 as a highly effective
The majority of carbonyl olefinations are typically catalyst for [2+2]cycloaddition and hydroamination
based on the reaction of an aldehyde 1 with a suitable of siloxy alkynes.[7] Such reactions were found to pro-
reagent 2, which transfers the alkylidene moiety to ceed under exceedingly mild conditions typically em-
give unsaturated product 3 with concomitant forma- ploying 1–5 mol% of this catalyst. In continuation of
tion of a stoichiometric amount of oxygenated prod- our systematic investigation of reactivity of electron-
uct 4 (Scheme 1).[1] The Arens carbonyl olefination rich alkynes,[8] we report herein the development of a
represents a highly effective and atom-economical al- silver-catalyzed Arens carbonyl olefination. Promoted
ternative to this process, which produces exclusively by a substoichiometric amount of AgNTf2, this trans-
the desired product 3 by employing a combination of formation represents a mild, efficient and highly che-
a carbonyl compound 1, alkyne 5 and an appropriate moselective method for conversion of aldehydes into
catalyst.[2] While extensive efforts have been devoted the corresponding unsaturated esters using siloxyal-
to advancing this olefination method, the reported kynes. Furthermore, excellent diastereoselectivities
transformations typically employ either large amounts were observed for a range of aldehydes using either
of highly reactive Lewis acids[3] or must be carried out 1-siloxy-1-propyne or 1-siloxy-1-hexyne.
at elevated temperatures.[4] The photochemical ver-
Our initial studies began with examination of the
sion of this process proceeds under mild conditions reaction of hexanal with 1-siloxy-1-propyne (Table 1,
albeit with low efficiency.[5] The use of highly nucleo- entry 1). We found that a substoichiometric amount
philic ynolates to affect this transformation has also of AgNTf2 was uniquely effective to enable the olefi-
been extensively investigated.[6] While significant ad- nation process. The optimum conditions entailed the
vances have been made, the development of a chemo- treatment of siloxyalkyne with a slight excess of alde-
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Jianwei Sun et al.
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Table 1. Ag-catalyzed olefination of aldehydes using 1-
siloxy-1-propyne or 1-siloxy-1-hexyne.
of crotonaldehyde and p-nitrobenzaldehyde also pro-
ceeded smoothly to give the expected products 9 and
10 as single geometrical isomers (Table 1, entries 4
and 5). Similarly, olefination of a range of aldehydes
using 1-siloxy-1-hexyne proved highly effective. The
corresponding products 11–16 (Table 1, entries 6–11)
were produced in excellent yields and high levels of
diastereoselectivity.
We also examined the effect of increasing steric
bulk of the siloxyalkyne on the efficiency and diaste-
reoselectivity of the olefination process. While treat-
ment of 2-cyclohexyl-1-siloxyacetylene with hexanal
produced the expected ester 17 in 72% yield (Table 2,
entry 1), the increased size of the siloxyalkyne con-
tributed to a notable decrease in the diastereoselectiv-
ity of this reaction. A similar trend was observed
during olefinations of aliphatic, unsaturated or aro-
matic aldehydes using 2-phenyl-1-siloxyacetylene
(Table 2, entries 2–4). The products were produced ef-
ficiently albeit with only moderate diastereoselectiv-
ity.
The mild reaction conditions, which were employed
during olefination of a range of aldehydes, suggested
to us that this catalytic process could be suitable for
the chemoselective olefination of aldehydes in the
presence of other carbonyl groups, such as esters or
even ketones. To test this hypothesis, we prepared al-
dehydes 21 and 22 bearing such functionalities
(Scheme 2). Subjection of both compounds to 1-
siloxy-1-hexyne under our standard conditions result-
ed in efficient and diastereoselective formation of the
corresponding silyl esters 23 and 24 arising from se-
lective functionalization of the aldehyde moiety. The
ability to effect a chemoselective olefination of alde-
hyde (1.1 equiv.) and 5 mol% of AgNTf2 at À788C, hydes in the presence of a ketone is particularly at-
followed by warming the reaction mixture to ambient
temperature and chromatographic purification to give
trisubstituted siloxy ester 6 in 87% yield as a single
Table 2. Ag-catalyzed olefination using cyclohexyl- and
detectable diastereomer. The efficiency and catalytic
phenyl-substituted siloxyalkynes.
turnover of this reaction compared favorably to the
protocol developed by Kowalski and co-workers,[3c]
which required the use of a stoichiometric amount of
TiCl4, and the olefination of aldimines reported by
Shindo and co-workers, which employed lantha-
nides.[9] A range of other possible reaction promoters,
including AgOTf, AuCl, AuCl3, PdCl2 and CuCl,
proved significantly less effective (0–9% conversion).
The use of Tf2NH (10 mol%) resulted in diminished
diastereoselectivity (2:1 dr), as well as lower reaction
efficiency (42% yield).
Having established the general catalytic protocol,
we next examined the substrate scope of this process.
The reactions of 1-siloxy-1-propyne with other ali-
phatic aldehydes proceeded equally efficiently in the
presence of 5 mol% of AgNTf2 to produce the corre-
sponding siloxy esters 7 and 8 with excellent diaste-
reoselectivities (Table 1, entries 2 and 3). Olefinations
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Adv. Synth. Catal. 2010, 352, 839 – 842

Silver-Catalyzed Aldehyde Olefination Using Siloxyalkynes
ering of the E-selectivity of the reaction when bulky
siloxyalkynes are employed.
In closing, we have described the development of a
mild, catalytic olefination of aldehydes using siloxyal-
kynes. Following our previous studies, we found that
AgNTf2 proved to be uniquely effective at promoting
this transformation with high efficiency and excellent
chemoselectivity. Furthermore, high levels of diaster-
eoselection were observed for a range of aldehydes
using either 1-siloxy-1-propyne or 1-siloxy-1-hexyne.
This process represents an important advance in the
Scheme 2. Chemoselective olefinations.
tractive in the context of potential applications of this area of catalytic Arens olefination and constitutes an
process in the area of complex molecule synthesis. alternative to the widely practiced Horner–Wads-
The working mechanistic hypothesis is outlined in worth–Emmons reaction.
Scheme 3. Our previous studies indicated that
AgNTf2 undergoes rapid and reversible coordination
to electron-rich alkynes. Even though aldehyde acti- Experimental Section
vation cannot be ruled out at this point, we propose
that the olefination begins with complexation of General Olefination Procedure
AgNTf2 with siloxyalkyne 25 to give an alkyne-silver
A
solution of siloxyalkyne (0.20 mmol) and aldehyde
complex, which can be represented as two resonance
structures 26 and 27.[7a] Subsequent addition to an al-
dehyde 28 affords an intermediate 29, which is next
converted to siloxyoxetene 30.[10] While the intermedi-
acy of 29 has not been proven experimentally thus
far, our previous work on [2+2]cycloadditions of sil-
(0.22 mmol) in CH2Cl2 (4 mL) was cooled to À788C under
an inert nitrogen atmosphere and treated with AgNTf2
(3.9 mg, 0.01 mmol). The reaction mixture was stirred at the
same temperature for 30 min, allowed to warm to room
temperature and stirred for another 30 min. The solvent was
removed under reduced pressure. The crude product was
purified directly by silica gel column chromatography. See
Supporting Information for additional experimental proto-
cols and analytical data.
ACHTUNGTRENNUNG
oxyalkynes,[7a] as well as relevant theoretical studies[11]
suggest that formation of the oxetene 30 is most
likely a step-wise process. Once formed, siloxyoxetene
30 is expected to undergo rapid conrotatory electocy-
clic ring-opening to give preferentially E-enoate 31
due to the predominant torquoselective outward rota- Acknowledgements
tion of the R2 group.[12] This mechanism provides an
Financial support of this work was provided by NSF
explanation for the high diastereoselectivity of the
olefination in the case of a small R1 substituent,
which originates from the siloxyalkyne. Furthermore,
the increased size of the R1 substituent is expected to
decrease the energetic preference for the torquoselec-
tive outward rotation of R2 group due to increased
steric repulsion between R1 and R2. The result is low-
CAREER (CHE-0447751) and NIH 1P50M086145.
References
[1] Modern Carbonyl Olefination: Methods and Applica-
tions, (Ed.: T. Tanaka), Wiley-VCH, Weinheim, 2004.
Scheme 3. Mechanistic hypothesis.
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Jianwei Sun et al.
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[2] a) H. Veiregge, H. J. T. Bos, J. F. Arens, Recl. Trav.
Chim. 1959, 78, 664–666; b) H. Veiregge, H. M.
Schmidt, J. Renema, H. J. T. Bos, J. F. Arens, Recl.
Trav. Chim. Pays-Bas 1966, 85, 929–951.
d) M. Shindo, K. Matsumoto, S. Mori, K. Shishido, J.
Am. Chem. Soc. 2002, 124, 6840–6841; e) M. Shindo,
Y. Sato, T. Yoshikawa, R. Koretsune, K. Shishido, J.
Org. Chem. 2004, 69, 3912–3916; f) M. Shindo, T.
Yoshikawa, Y. Itou, S. Mori, T. Nishii, K. Shishido,
Chem. Eur. J. 2006, 12, 524–536; g) M. Shindo, T. Kita,
T. Kumagai, K. Matsumoto, K. Shishido, J. Am. Chem.
Soc. 2006, 128, 1062–1063; h) T. Yoshikawa, S. Mori,
M. Shindo, J. Am. Chem. Soc. 2009, 131, 2092–2093.
[7] a) R. Sweis, M. P. Schramm, S. A. Kozmin, J. Am.
Chem. Soc. 2004, 126, 7442–7443; b) J. Sun, S. A.
Kozmin, Angew. Chem. 2006, 118, 5113–5115; Angew.
Chem. Int. Ed. 2006, 45, 4991–4993.
[8] a) M. P. Schramm, D. S. Reddy, S. A. Kozmin, Angew.
Chem. 2001, 113, 4404–4407; Angew. Chem. Int. Ed.
2001, 40, 4274–4277; b) D. S. Reddy, S. A. Kozmin, J.
Org. Chem. 2004, 69, 4860–4862; c) L. Zhang, S. A.
Kozmin, J. Am. Chem. Soc. 2004, 126, 10204–10205;
d) L. Zhang, S. A. Kozmin, J. Am. Chem. Soc. 2004,
126, 11806–11807; e) J. Sun, S. A. Kozmin, J. Am.
Chem. Soc. 2005, 127, 13512–13513; f) J. Sun, M. P.
Conley, L. Zhang, S. A. Kozmin, J. Am. Chem. Soc.
2006, 128, 9705–9710.
[3] a) S. I. Pennanen, Tetrahedron Lett. 1980, 21, 657–658;
b) J. Pornet, A. Rayadh, L. Miginiac, Tetrahedron Lett.
1986, 27, 5479–5482; c) C. J. Kowalski, S. Sakdarat, J.
Org. Chem. 1990, 55, 1977–1979; d) J. Sisko, A. Balog,
D. P. Curran, J. Org. Chem. 1992, 57, 4341–4342; e) D.
Zakarya, A. Rayadh, M. Samih, T. Lakhlifi, Tetrahe-
dron Lett. 1994, 35, 2345–2348; f) A. Hayashi, M. Ya-
maguchi, M. Hirama, Synlett 1995, 195–196; g) M.
Oblin, J.-L. Parrain, M. Rajzmann, J.-M. Pons, Chem.
Commun. 1998, 1619–1620; h) G. S. Viswanathan, C.-J.
Li, Tetrahedron Lett. 2002, 43, 1613–1615; i) K. C. M.
Kurtz, R. P. Hsung, Y. Zhang, Org. Lett. 2006, 8, 231–
234; j) L. You, Z. F. Al-Rashid, R. Figueroa, S. K.
Ghosh, G. Li, T. Lu, R. P. Hsung, Synlett 2007, 1656–
1662.
[4] a) M. Curini, F. Epifano, F. Maltese, O. Rosati, Synlett
2003, 552–554; b) J. U. Rhee, M. J. Krische, Org. Lett.
2005, 7, 2493–2495; c) T. Jin, Y. Yamamoto, Org. Lett.
2007, 9, 5259–5262; d) A. Saito, M. Umakoshi, N.
Yagyu, Y. Hanzawa, Org. Lett. 2008, 10, 1783–1785.
[5] a) G. Bꢁchi, J. T. Kofron, E. Koller, D. Rosenthal, J.
Am. Chem. Soc. 1956, 78, 876–877; b) L. E. Friedrich,
J. D. Bower, J. Am. Chem. Soc. 1973, 95, 6869–6870.
[6] a) C. J. Kowalski, K. W. Fields, J. Am. Chem. Soc. 1982,
104, 321–323; b) M. Shindo, Y. Sato, K. Shishido, Tetra-
hedron Lett. 1998, 39, 4857–4860; c) M. Shindo, Y.
Sato, K. Shishido, J. Org. Chem. 2000, 65, 5443–5445;
[9] M. Shindo, O. Soichiro, Y. Sato, K. Shishido, Heterocy-
cles 2000, 52, 545–548.
[10] W. J. Middleton, J. Org. Chem. 1965, 30, 1307.
[11] M. Oblin, M. Rajzmann, J.-M. Pons, Tetrahedron 2001,
57, 3099–3104.
[12] W. R. Dolbier, H. Koroniak, K. N. Houk, C. Sheu, Acc.
Chem. Res. 1996, 29, 471–477.
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