Scheme 2. In Situ Generation and Reaction of
B-Allenyl-9-BBN
Table 1. Propargylation of Representative Carbonyl
Compounda
entry
substrate
no.
yield (%)b
1
2
3
4
5
6
7
8
9
R-methyl-trans-cinnamaldehyde
PhCHO
CyCHO
4-methoxybenzaldehyde
4-nitrobenzaldehyde
acetophenone
cyclopentanone
cyclohexanone
2
3
4
5
6
7
8
9
10
99
96
91
99
94
97
88
94
88
allylation afforded bishomoallylic alcohols as either antipode
in excellent yield.5 We speculated that this approach might
be modified to allow for propargylation of the in situ-
generated electrophiles (Scheme 1).6 This would improve
the general utility of employing 2-vinyloxiranes as surrogates
to â,γ-unsaturated aldehydes and afford a versatile route to
an important class of substrates due to the ready availability
of the starting materials. Moreover, compared to our earlier
accounts on allylation,4,5 the products would have clearly
differentiated π-systems useful for further elaboration. In this
report, we describe the successful realization of this objective,
allowing efficient access to homoallylic homopropargylic
alcohols.
There are numerous methods to effect the propargylation
of aldehydes that utilize various allenyl- or propargylorgano-
metallics.7 Our previous success of boron-based allylation
and crotylation4,5 protocols suggested that B-allenyl-9-
BBN7a,b (1) might offer the most promise to effect the desired
transformation (Scheme 1). This reagent (1) is known7a,b to
be highly reactive and importantly exhibits excellent selec-
tivity in favor of the homopropargylic product.
pinacolone
a All reactions were performed on a 1.6 mmol scale. b Isolated yield.
Et2O) and stirred for 2 h at -78 °C. After warming to room
temperature, analysis by 11B NMR indicated formation of 1
(δ 79 ppm, >90% purity by 11B NMR) in both cases.
Addition of R-methyl-trans-cinnamaldehyde to the hetero-
geneous mixtures gave the desired propargylated product 2
in good yield (Scheme 2). In particular, this was especially
true for B-allenyl-9-BBN derived from B-bromo-9-BBN. We
note that none of the corresponding allenic alcohol was
1
observed in the H NMR spectrum of the crude reaction
mixture.
Neat B-allenyl-9-BBN, free from magnesium salts, is
easily prepared on a large scale from B-bromo-9-BBN by
drying crude 1 under high vacuum, filtration under nitrogen
using pentane, followed by removal of the solvent. Addition
of ether affords solutions that can be utilized directly to effect
propargylation of a wide variety of aldehydes (Table 1,
entries 1-5) and ketones (Table 1, entries 6-9) in excellent
yield. Distillation of 1 is not required, and in no cases (Table
1, entries 1-9), even with pinacolone (Table 1, entry 9),
were any of the corresponding allenic alcohols observed.
These results are fully consistent with those previously
reported with purified B-allenyl-9-BBN synthesized from
B-chloro-9-BBN.7a,b
B-Allenyl-9-BBN is synthesized7b in high yield from
B-chloro-9-BBN8 and allenylmagnesium bromide.9 However,
in our hands, B-chloro-9-BBN proved to be inconvenient to
synthesize due to the numerous manipulations of very
sensitive compounds required. We speculated that either the
commercially available (Aldrich) B-bromo-9-BBN or 9-BBN
triflate might be a suitable substitute and allow for an
expedient synthesis of this reagent (1).
Attention was then focused on finding suitable conditions
compatible with the rearrangement of 2-vinyloxiranes to â,γ-
unsaturated aldehydes. Optimization studies were performed
using the vinyl epoxide derived from R-methyl-trans-
cinnamaldehyde (11). Attempts to apply the in situ developed
conditions (Scheme 2) failed under all circumstances, which
was consistent with prior results where magnesium salts were
observed to interfere.5,10 However, salt-free etheral solutions
of 1 gave the desired product (12) in reasonable yields (55%)
with Sc(OTf)3 (7.5 mol %). We were unable to improve the
yield by modification of any of the reaction parameters in
this solvent. THF solutions of 1 displayed an 11B NMR
resonance at δ 16 ppm, suggesting that B-allenyl-9-BBN
exists predominantly as a THF adduct. Whereas coordination
Solutions of B-bromo-9-BBN (1 M in CH2Cl2) or 9-BBN
triflate (0.5 M in hexanes) were treated with 1 equiv of
freshly prepared allenylmagnesium bromide (∼0.8 M in
(5) Lautens, M.; Maddess, M. L.; Sauer, E. L. O.; Ouellet, S. G. Org.
Lett. 2002, 4, 83.
(6) A similar indium-mediated transformation has been developed by
Pae that includes a few examples for synthesis of homoallylic homopro-
pargylic alcohols, albeit as mixtures of addition products; see: Oh, B. K.;
Cha, J. H.; Cho, Y. S.; Choi, K. I.; Koh, H. Y.; Chang, M. H.; Pae, A. N.
Tetrahedron Lett. 2003, 44, 2911.
(7) See references cited in the following works: (a) Brown, H. C.; Khire,
U. R.; Racherla, U. S. Tetrahedron Lett. 1993, 34, 15. (b) Brown, H. C.;
Khire, U. R.; Narla, G.; Racherla, U. S. J. Org. Chem. 1995, 60, 544.
(8) (a) Brown, H. C.; Dhar, R. K.; Ganesan, K.; Singaram, B. J. Org.
Chem. 1992, 57, 499. (b) Brown, H. C.; Ravindran, N.; Kulkarni, S. U. J.
Org. Chem. 1979, 44, 1979. (c) Kramer, G. W.; Brown, H. C. J. Organomet.
Chem. 1974, 73, 1 (d) Brown, H. C.; Kulkarni, S. U. J. Organomet. Chem.
1979, 79, 281.
(9) Hopf, H.; Bohm, I.; Kleinschroth, J. Org. Synth. 1982, 60, 41.
(10) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401.
Org. Lett., Vol. 7, No. 16, 2005
3558