aryl- and alkenylboronic acids can be conveniently prepared
by a variety of methods.7
Initial screening of reaction conditions with compound 1a
led to [(cod)2Rh]BF4 and Ba(OH)2 as the best choices in
catalyst and base for the tandem conjugate addition-Michael
cyclization process.
Reaction of compound 1a with arylboronic acids (Table
1, entries 1-5) took place with good yield and diastereo-
The success of a tandem process initiated by the conjugate
addition of an organorhodium compound to an unsaturated
carbonyl functional group (FG1) relies on the adequate choice
of a secondary functional group (FG2) suitably placed in the
starting material. FG2 must not react intermolecularly with
the R2-RhI compound, but must be reactive enough to trap
intramolecularly the oxa-π-allyl-RhI intermediate A generated
in the conjugate addition step (Scheme 1).
Table 1. Addition of RB(OH)2 to Ketones 1a-ca
Scheme 1. Tandem Process Triggered by Conjugate Addition
In addition, A must be stable enough as not to be
protonated in the organic solvent-H2O reaction medium
usually used in these reactions.
In this regard, the combination of enone (FG1) and ketone
(FG2), i.e., tandem conjugate addition-aldol reaction, has
been reported to produce cyclic aldols in a stereoselective
fashion,8 and the combination of R,â-unsaturated ester (FG1)
and nitrile (FG2) has been reported to produce cyclic
â-enamino esters.9
a Reactions carried out at room temperature with 0.2 mmol of substrates
1, 1.5 equiv of RB(OH)2, and 1.0 equiv of base with 5 mol % of RhI with
respect to 1 in 0.5 mL of dioxane-H2O (10:1). b Yield of the isolated
product mixture after column chromatography on silica gel. c Product ratio
1
determined by integration of the H NMR signals of the reaction crudes.
We report herein the first examples of the stereoselective
sequence RhI-catalyzed tandem conjugate addition of aryl-
boronic acids to enones-Michael cyclization (FG1 ) enone,
FG2 ) enone). Compounds 1 (Scheme 2) have been chosen
selectivity in favor of the 1,2-trans-2,3-trans-indans 2a, with
the exception of p-F-C6H4-B(OH)2 (entry 4) and o-MeO-
C6H4-B(OH)2 (entry 5), which afforded the corresponding
products with low diastereoselectivity. Therefore, the reac-
tions of 1a are sensible both to electronic (para electron-
withdrawing group) and steric (ortho electron-donating
group) effects. In addition, the tandem process was also
successful for the addition of vinylboronic acids (entry 6),
which took place with good yield and diastereoselectivity.
On the other hand, the 1,2-trans-2,3-trans-indans 2b were
obtained in a highly diastereoselective fashion when com-
pounds 1b were used as starting materials (Table 1, entries
7-12), for the reaction with both aryl- and vinylboronic
Scheme 2. Addition of RB(OH)2 to Esters 3-5
(8) (a) Cauble, D. F.; Gipson, J. D.; Krische, M. J. J. Am. Chem. Soc.
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as starting materials to produce 1,2,3-trisubstitued indans,
which constitute relevant pharmaceutical scaffolds.10
(7) For recent leading references on the synthesis of boronic acids and
derivatives, see: (a) Kalinin, A. V.; Scherer, S.; Snieckus, V. Angew. Chem.,
Int. Ed. 2003, 42, 3399. (b) Zhu, W.; Ma, D. Org. Lett. 2006, 8, 261. (c)
Stefani, H. E.; Cellab, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623. (d)
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and references therein cited.
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