As part of ongoing studies on the synthesis and reactivity
of organotrifluoroborate salts,10 we have recently developed
a new class of allyl/crotylboron reagents, potassium allyl-
and crotyltrifluoroborates 1a-c, and reported their Lewis
acid-promoted additions to carbonyl compounds.10a,b In the
course of developing milder reaction conditions, we discov-
ered that 1a undergoes facile addition to aldehydes 2 in a
biphasic medium containing a phase transfer catalyst (PTC).
A variety of PTCs (10 mol %) promote the allylation of
4-bromobenzaldehyde (1.0 equiv) by potassium allyltrifluo-
roborate 1a (1.1 equiv) in a biphasic reaction medium (CH2-
Cl2/H2O, 15 min at rt),11 including quaternary ammonium
and phosphonium halide salts (Table 1). In the absence of a
Table 2. Allylation of Aldehydes 2a-k by Potassium
Allyltrifluoroborate 1a in a Biphasic Medium Containing Bu4NI
(10 mol %)
n
entry
R3
homoallylic alcohol
yielda [%]
1
2
3
4
5
6
7
8
9
4-BrC6H4
(CH3)3C
C7H15
3a
3b
3c
3d
3e
3f
3g
3h
3i
99
95
94
97
99
98
99
97
98
95
95
Chx
2-O2NC6H4
4-MeOC6H4
3-HOC6H4
4-MeO2CC6H4
4-NCC6H4
(E)-PhHCdCH
2-furanyl
Table 1. Comparative Efficiency of Various Phase Transfer
Catalysts (PTCs) (10 mol %) in the Addition of Potassium
Allyltrifluoroborate 1a (1.10 equiv) to 4-Bromobenzaldehyde
10
11
3j
3k
a Isolated yields. See ref 11.
organic phase with reaction presumably occurring at the
interface of the aqueous and organic phases.12
entry
PTCa
yielda [%]
More significantly, crotylations of aliphatic, aromatic, and
R,â-unsaturated aldehydes could also be accomplished using
the same reaction conditions, occurring with excellent
diastereoselectivities and high yields (Table 3). The use of
potassium (Z)-crotyltrifluoroborate 1b led to the formation
of syn homoallylic alcohols (dr g 98:2), while the (E)-crotyl
reagent 1c afforded anti adducts (dr g 98:2). To the best of
our knowledge, this represents the first general method for
the selective generation of either syn or anti homoallylic
alcohols 4 in biphasic or aqueous media.13
The simplicity, high diastereoselectivity, and simple
workup protocol should render this protocol attractive for
parallel/combinatorial synthesis or for reactions where enan-
tioselectivity14 is not important. For large-scale reactions, or
reactions where removal of the PTC may be problematic,
reaction of aldehydes with 1 in biphasic media can be carried
out in the absence of the PTC, but the reaction times are
significantly lengthened. We found that all of the aldehydes
tested reacted completely within 16 h to furnish the corre-
sponding homoallylic alcohols in high yields and diastereo-
selectivity, without the necessity of further purification.
A number of experiments were conducted in order to
deduce the mode of reactivity of 1. The allylation of 2a (1
1
2
3
4
5
none
15
99
98
97
97
nBu4NI
nBu4NBr
BnEt3NCl
Ph3MePCl
a Isolated yields. See ref 11.
PTC, the reaction was found to be rather sluggish (15% yield
after 15 min at rt) and was incomplete after 15 min if less
than 10 mol % PTC was used.
The scope of the transformation was established with a
variety of different aldehydes using nBu4NI as the PTC (Table
2). Aliphatic, aromatic, R,â-unsaturated, and heterocyclic
aldehydes were efficiently allylated in very high yields
(g94%), tolerating nitro, ester, and cyano groups, aromatic
halides, and an unprotected phenol. In the case of cinnama-
ldehyde, only 1,2-addition was observed. Non-chlorinated
organic solvents (e.g., toluene or diethyl ether) can also be
used under the biphasic conditions without affecting the
product yield. The additions can also be accomplished within
15 min in water alone as long as a PTC (10 mol %) is
present. If a water-soluble aldehyde (such as 2k) is used,
then the PTC is unnecessary. The presumed role of the phase
transfer catalyst in these reactions is to transport the
allyltrifluoroborate anion from the aqueous phase into the
(12) For a recent monograph on phase transfer catalysis, see: Handbook
of Phase Transfer Catalysis; Sasson, Y., Neumann, R. Eds.; Blackie
Academic & Professional: London, 1997.
(13) Reaction of specific indium reagents derived from functionalized
allyl bromides with aldehydes proceeds in some cases with high diaste-
reoselectivity, see: (a) Li, X.-R.; Loh, T.-P. Tetrahedron: Asymmetry 1996,
7, 1535-1538. (b) Isaac, M. B.; Paquette, L. A. J. Org. Chem. 1997, 62,
5333-5338. (c) Loh, T.-P.; Li, X.-R. Eur. J. Org. Chem. 1999, 1893-
1899. (d) Canac, Y.; Levoirier, E.; Lubineau, A. J. Org. Chem. 2001, 66,
3206-3210.
(14) Not surprisingly, the use of chiral PTCs did not result in enanti-
oselective addition. For leading references on chiral PTCs, see: Dalko, P.
I.; Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726-3748.
(10) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V.; Lough, A. J. Synthesis
2000, 990-998. (b) Batey, R. A.; Thadani, A. N.; Smil, D. V. Tetrahedron
Lett. 1999, 40, 4289-4292. (c) Batey, R. A.; Quach, T. D. Tetrahedron
Lett. 2001, 42, 9099-9103. (d) Batey, R. A.; Thadani, A. N.; Smil, D. V.
Org. Lett. 1999, 1, 1683-1686.
(11) Isolated yields reported after separation of the layers, extraction (3
× 5 mL, CH2Cl2), removal of the solvent, and passage of the resulting
crude reaction mixture through a short plug of silica gel (EtOAc as the
eluent) in order to remove the PTC.
3828
Org. Lett., Vol. 4, No. 22, 2002