A facile, one-pot synthesis of β-substituted (Z)-acrylonitriles utilizing an α-diaminoboryl carbanion

Article abstract of DOI:10.1021/ol100534s

A simple three-step single-pot procedure for Z-stereoselective synthesis of β-monosubstituted acrylonitriles has been established. The reaction involves olefination of aldehydes with an in situ generated α-diaminoboryl carbanion species. Various aromatic and aliphatic aldehydes were smoothly converted into the corresponding (Z)-olefin products (up to 96:4 ratio) in good yields (80-98%).

Full text of DOI:10.1021/ol100534s

ORGANIC
LETTERS
2010
Vol. 12, No. 10
2171-2173
A Facile, One-Pot Synthesis of
ꢀ-Substituted (Z)-Acrylonitriles Utilizing
an r-Diaminoboryl Carbanion
Takashi Tomioka,* Yusuke Takahashi, Trey G. Vaughan, and Takayoshi Yanase
Department of Chemistry and Biochemistry, UniVersity of Mississippi,
UniVersity, Mississippi 38677
tomioka@olemiss.edu
Received March 4, 2010
ABSTRACT
A simple three-step single-pot procedure for Z-stereoselective synthesis of ꢀ-monosubstituted acrylonitriles has been established. The reaction
involves olefination of aldehydes with an in situ generated r-diaminoboryl carbanion species. Various aromatic and aliphatic aldehydes were
smoothly converted into the corresponding (Z)-olefin products (up to 96:4 ratio) in good yields (80-98%).
A variety of ꢀ-substituted acrylonitriles are useful intermedi-
ates in organic synthesis, and their common functional
moiety, R,ꢀ-unsaturated cyanide, is often utilized as (1) a
Michael reaction acceptor,1 (2) a Heck coupling partner,2
and (3) an activated alkene in the Baylis-Hilman reaction,3
etc.4 Many of those acrylonitriles are typically prepared from
an aldehyde by means of phosphorus- or silicon-based
olefination in a stereoselective manner (e.g., Wittig/
Horner-Emmons5,6 and Peterson7,8 type reactions). How-
ever, in practice, Z-stereoselective conditions6,8,9 are still
limited and less accomplished in terms of the overall reaction
efficiency as well as operational simplicity.
As an R-phosphoryl and silyl carbanion species, R-boryl
carbanion10 exhibits an excellent olefinating ability.11-14
However, the Lewis acidic nature of the boron often
complicates the base-induced carbanion generation step,
deprotonation of R-hydrogen, as a result of the use of a strong
base, which preferentially leads to an undesired “ate”
(6) (a) Moison, H.; Texier-Boullet, F.; Foucaud, A. Tetrahedron 1987,
43, 537. (b) Zhang, T. Y.; O’Toole, J. C.; Dunigan, J. M. Tetrahedron
Lett. 1998, 39, 1461. (c) Kojima, S.; Kawaguchi, K.; Matsukawa, S.; Uchida,
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A.; Ikeda, N.; Yamamoto, H. Chem. Lett. 1982, 1093. (c) Furuta, K.;
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2002, 4, 4723. (c) You, J.; Xu, J.; Verkade, J. G. Angew. Chem., Int. Ed.
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Chem. 1980, 45, 4767. (b) Lee, D.; Yang, Y.; Yun, J. Org. Lett. 2007, 9,
2749. (c) Grigg, R.; Sridharan, V.; Shah, M.; Mutton, S.; Kilner, C.;
MacPherson, D.; Milner, P. J. Org. Chem. 2008, 73, 8352. (d) Worlikar,
S. A.; Larock, R. C. Org. Lett. 2009, 11, 2413.
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Soc., Chem. Commun. 1982, 56. (b) Matsuda, I.; Okada, H.; Izumi, Y. Bull.
Chem. Soc. Jpn. 1983, 56, 528. (c) Crowe, W. E.; Goldberg, D. R. J. Am.
Chem. Soc. 1995, 117, 5162. (d) Randl, S.; Gressler, S.; Wakamatsu, H.;
Blechert, S. Synlett 2001, 430. (e) Peppe, C.; Mello, P. A.; dasChagas, R. P.
J. Organomet. Chem. 2006, 691, 2335.
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Foucaud, A. Tetrahedron 1985, 41, 1259. (b) Daniel, H.; Le Corre, M.
Tetrahedron Lett. 1987, 28, 1165. (c) Antonioletti, R.; Bonadies, F.;
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therein.
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10.1021/ol100534s  2010 American Chemical Society
Published on Web 04/28/2010

complex rather than a carbanion. To overcome this major
drawback, Rathke, Pelter, and Matteson have successfully
found effective solutions: (1) the use of a sterically hindered
non-nucleophilic base (LiTMP),11,15 (2) the use of a sterically
hindered dimesityl borane,12,16 and (3) the use of an electron-
rich dialkoxyborane.13,17 These primary studies clearly
indicate that efficient deprotonation relies heavily on two
major parameters: steric shielding and electronic factors
around boron.
conversion). Interestingly, the observed major stereoisomer
was a thermodynamically less stable Z-form (Z:E ) ∼4:1).
Attempts to examine the effects of different solvent (Et2O),
reaction temperature (-40 °C), base (KHMDS, LDA, and
LiTMP), and additive (TMEDA) led to inferior stereoselec-
tivity and/or conversion.
Scheme 1. Initially Attempted One-Pot Olefination
Interestingly, among a variety of organoborane species, a
diaminoboryl group “(R2N)2B-” has an exceptionally mild
Lewis acidic property due to the strong back-donation of
electron density from nitrogen’s lone pair electrons to boron’s
vacant p orbital.18,19 Since such an electron-rich diaminoboryl
group is seemingly highly base-compatible, and also the
sterically tunable amino ligand can protect the boron site
from a base and/or a nucleophile, those two key functions
are particularly advantageous for the study of R-boryl
carbanion chemistry. Although an electron-rich boryl system
often decreases stabilization of an adjacent carbanion species
as a result of the lowering of boron’s π-accepting nature,
attachment of an appropriate electron-withdrawing and/or
anion-stabilizing functional group on the R-carbon should
help to form a stable carbanion species as well as increase
the acidity of R-hydrogens. On the basis of these assump-
tions, we anticipated that a diaminoboryl acetonitrile
(R2N)2BCH2CN would be an ideal olefinating reagent for
the synthesis of ꢀ-substituted acrylonitrile. To the best of
our knowledge, there is no general synthetic path to access
such boryl acetonitriles, though the ate complex form
(KBF3CH2CN) was recently reported by the Molander
group.20
Although a sterically hindered non-nucleophilic base
(LHMDS, etc.) was initially employed to avoid the formation
of an undesired “ate” complex, further optimization revealed
that even treating 1 with 2 equiv of nucleophilic LiCH2CN
followed by the addition of an aldehyde still gave desired
product in excellent yield (94%) with (Z)-stereoselectivity
(Z:E ) 82:18). This implies that, following the formation
of borylacetonitrile, the remaining LiCH2CN (1 equiv) was
effectively utilized as a base to form a corresponding
carbanion 2 (Scheme 2). [Note: the use of a sterically less
demanding diaminoboryl reagent, (Me2N)2BBr,22 did not give
satisfactory results but instead afforded a low yield of product
(<60%) plus formation of a side adduct,23 under the reaction
conditions. In addition, the major stereoisomer was an (E)-
olefin (Z:E ) ∼1:2).]
To begin, a four-step single-pot procedure comprising (i)
preparation of lithioacetonitrile, (ii) formation of boryl
acetonitrile, (iii) generation of an R-boryl carbanion, and (iv)
olefination of an aldehyde was initially designed/tested
(Scheme 1). The use of a readily available bis(diisopropy-
lamino)chloroborane reagent 121 successfully gave desired
Scheme 2. Optimized One-Pot Olefination
1
olefination products based on H NMR evidence (∼80%
(12) (a) Pelter, A.; Singaram, B.; Wilson, J. W. Tetrahedron Lett. 1983,
24, 635. (b) Pelter, A.; Buss, D.; Pitchford, A. Tetrahedron Lett. 1985, 26,
5093. (c) Pelter, A.; Buss, D.; Colclough, E. J. Chem. Soc., Chem. Commun.
1987, 297. (d) Pelter, A.; Smith, K.; Elgendy, S.; Rowlands, M. Tetrahedron
Lett. 1989, 30, 5643. (e) Pelter, A.; Smith, K.; Elgendy, S.; Rowlands, M.
Tetrahedron Lett. 1989, 30, 5647. (f) Pelter, A.; Buss, D.; Colclough, E.;
Singaram, B. Tetrahedron 1993, 49, 7077. (g) Pelter, A.; Smith, K.; Elgendy,
S. M. A. Tetrahedron 1993, 49, 7119. (h) Pelter, A.; Peverall, S.; Pitchford,
Table 1 illustrates several representative aldehydes exam-
ined. Various aromatic aldehydes including ortho-, meta-,
and para-substituted benzaldehydes (entries 1-4) consis-
tently led to decent (Z)-stereoselectivity (Z:E ) ∼80:20),
although an ortho-substituted system was slightly less
selective than the others. A heteroaromatic furfural was also
smoothly converted into the desired (Z)-olefination product
(entry 5). Interestingly, aliphatic aldehydes bearing an
R-acidic proton (entries 6 and 7) still exclusively gave the
corresponding olefinic products in excellent yield without
A. Tetrahedron 1996, 52, 1085
(13) (a) Matteson, D. S.; Moody, R. J. Organometallics 1982, 1, 20.
(b) Matteson, D. S.; Majumdar, D. Organometallics 1983, 2, 230
.
.
(14) (a) Castle, R. B.; Matteson, D. S. J. Organomet. Chem. 1969, 20,
19. (b) Matteson, D. S; Tripathy, P. B. J. Organomet. Chem. 1970, 21, P6.
(c) Matteson, D. S.; Moody, R. J.; Jesthi, P. K. J. Am. Chem. Soc. 1975,
97, 5608. (d) Matteson, D. S.; Moody, R. J. J. Org. Chem. 1980, 45, 1091.
(e) Tsai, D. J. S.; Matteson, D. S. Organometallics 1983, 2, 236. (f)
Matteson, D. S.; Wilson, J. W. Organometallics 1985, 4, 1690
(15) Kow, R.; Rathke, M. W. J. Am. Chem. Soc. 1973, 95, 2715
(16) (a) Pelter, A.; Singaram, B.; Williams, L.; Wilson, J. W. Tetrahe-
dron Lett. 1983, 24, 623. (b) Pelter, A. Pure Appl. Chem. 1994, 66, 223
(17) (a) Matteson, D. S.; Moody, R. J. J. Am. Chem. Soc. 1977, 99,
.
.
.
3196. (b) Matteson, D. S.; Arne, K. J. Am. Chem. Soc. 1978, 100, 1325
.
(18) Hadebe, S. W.; Robinson, R. S. Eur. J. Org. Chem. 2006, 4898
.
(21) Haberecht, J.; Krummland, A.; Breher, F.; Gebhardt, B.; Ruegger,
H.; Nesper, R.; Grutzmacher, H. Dalton Trans. 2003, 2126.
(22) Available from Sigma-Aldrich (product no. 476668).
(23) PhCH(OH)CH2CN.
(19) Suginome, M.; Uehlin, L.; Yamamoto, A.; Murakami, M. Org. Lett.
2004, 6, 1167
.
(20) Molander, G. A.; Ham, J. Org. Lett. 2006, 8, 2031.
2172
Org. Lett., Vol. 12, No. 10, 2010

competitive enolization. The use of sterically congested
aldehydes (entries 8-11) greatly improved the Z/E ratio to
96:4. However, a structurally much less hindered aldehyde,
trans-cinnamaldehyde (entry 12), resulted in low (Z)-
stereoselectivity.
aldehyde and the diaminoboryl reagent. In contrast, the
electronic factor of the reactant seems far less significant on
the basis of comparisons of selectivities among benzaldehyde,
p-tolualdehyde, and p-anisaldehyde. Although the exact
mechanism is unclear at this point, the Bassindale-Taylor
model of steric approach control,24 which reasonably explains
the (Z)-stereoselective outcome in the Peterson-type olefi-
nation, may be applicable in explaining our olefination
mechanism. Thus, the use of a bulky diaminoboryl reagent
as well as aldehyde would preferentially lead to an erythro
oxyanion intermediate 4 (or anionic oxaboratane species)
through the carbanion approach model 3 (Scheme 3).
Subsequently, a possible syn elimination of 4 should afford
the (Z)-olefin product as the major isomer.
Table 1. One-Pot Synthesis of ꢀ-Substituted (Z)-Acrylonitriles
Scheme 3.
Plausible Z-Stereoselective Olefination Mechanisma
a S, M, and L represent small, medium, and large substituents,
respectively.
In summary, a simple three-step single-pot procedure for
the synthesis of a ꢀ-monosubstituted (Z)-acrylonitrile, em-
ploying a novel R-diaminoboryl carbanion mediated olefi-
nation, has been established. A variety of aromatic and
aliphatic aldehydes were efficiently converted into the
corresponding (Z)-olefin product. In addition, our approach
utilizing a mildly Lewis acidic diaminoboryl group success-
fully overcame a common technical difficulty to access an
R-boryl carbanion, which is a potentially versatile species
in organic synthesis. Further application of an R-diaminobo-
ryl carbanion system to a wide range of electrophiles is
currently under investigation in our laboratory.
Acknowledgment. The University of Mississippi sup-
ported this research.
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
a
Determined by H NMR of the crude reaction mixture. b Combined
1
isolated yield of Z and E isomers. c NMR yield (internal standard).
OL100534S
(24) (a) Bassindale, A. R.; Ellis, R.; Lau, J. C.-Y.; Taylor, P. G. J. Chem.
Soc., Perkin Trans. 2 1986, 593. (b) Bassindale, A. R.; Ellis, R. J.; Lau,
J. C.-Y.; Taylor, P. G. J. Chem. Soc., Chem. Commun. 1986, 98.
These experimental results indicate that the stereoselec-
tivity correlates well with the steric factors of both the
Org. Lett., Vol. 12, No. 10, 2010
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