J . Org. Chem. 1997, 62, 4643-4649
4643
P h en yl-Ca r bon yl Cou p lin g Rea ction s P r om oted by Sa m a r iu m
Diiod id e a n d Hexa m eth ylp h osp h or a m id e
J iann-Shyng Shiue, Mei-Huey Lin, and J im-Min Fang*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, Republic of China
Received February 11, 1997X
By mediation of samarium diiodide and hexamethylphosphoramide, benzaldehydes and acetophe-
nones underwent self- and cross-couplings to give the products having linkages at the para-carbons
of phenyl rings and the carbonyl groups. The phenyl-carbonyl coupling of 2,5-dimethoxybenzal-
dehyde generated a Sm(III)-enolate intermediate, which was trapped by alkyl halides in a
stereospecific manner to give uncommon 1,4-dialkyl-2,5-cyclohexadiene-1-carboxaldehydes. The
benzaldehydes bearing tethered carbonyl chains proceeded with intramolecular phenyl-carbonyl
couplings to afford fused benzocycles.
In tr od u ction
Benzaldehydes are reduced with SmI2 in THF to give
the corresponding benzyl alcohols 2 in the presence of a
protic cosolvent such as MeOH or t-BuOH.5a In the
absence of protic solvent, aromatic aldehydes or aromatic
ketones couple readily to give pinacols 3 (the hydrodimer-
ization products) on treatment with 1 equiv of SmI2 in
THF.7 If less than 1 equiv of SmI2 is employed to react
with benzaldehyde, several products including benzyl
alcohol, hydrobenzoin, benzoin, and benzyl benzoate are
obtained.8 We reported9 previously that various benzal-
dehydes undergo phenyl-carbonyl couplings to give the
dimerization products, such as 4a -g, by mediation of
SmI2/HMPA in THF (Scheme 1). The coupling occurs at
the para-carbon of benzaldehyde, differing from the meta-
directing Friedel-Crafts reactions of the benzenes con-
taining electron-withdrawing substituents. The yields of
4a -g vary from 18 to 80% depending on substrates and
reaction conditions, while significant amounts (up to 50%)
of the aldehyde substrates are often recovered. An
optimal yield (80%) of 4a was obtained when the reaction
was conducted with ratios PhCHO/SmI2/HMPA ) 1:2:8.
The dipolar additive HMPA appears to play a crucial role
to prevent the aromatic carbonyls from reduction or
pinacol coupling (see Scheme 5 for discussion of the
reaction mechnism). Additives such as DMF, TMEDA,
N-methylpyrrolidinone (NMP), and N,N-dimethylacet-
amide (DMA) are inferior to HMPA in promoting the
formation of the dimers. These additives yield black
gelatinous precipitates and lower reactivity severely.
Benzaldehydes bearing MeO, Me, and Cl substituents at
either ortho- or meta-positions also undergo the phenyl-
carbonyl couplings at the para-carbons, giving the dimers
4b-g. However, the phenyl-carbonyl coupling reactions
Samarium(II) iodide is a useful one-electron-transfer
reducing agent.1 A variety of additives have been used
with SmI2 to effect organic reactions. For example,2
bases like KOH, LiOMe, and LiNH2 can be used with
SmI2 in the reductions of esters, amides, and oximes. The
Lewis acids FeCl3, CoCl2, and NiCl2 are used with SmI2
to accelerate reductions of alkynes.2d,3 Intramolecular
halide-carbonyl and ketyl-olefin couplings are carried
out by SmI2 along with FeCl2, FeCl3, Fe(acac)3, tris-
(dibenzoylmethido)iron(III), or Cp2ZrCl2.4 A dipolar co-
solvent HMPA is a general and effective additive to
facilitate the above-mentioned and other reactions5 such
as the reduction of halides, cleavage of carbon-sulfur
bonds, deoxygenation of sulfones, and halide-olefin
couplings. Other dipolar cosolvents6 such as 1,3-di-
methyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU)
and tripiperidinophosphine oxide (C5H10N)3PO are oc-
casionally utilized as a substitute for HMPA.
X Abstract published in Advance ACS Abstracts, J uly 1, 1997.
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