We have developed a new umpolung strategy for catalytically forming a chiral α-alkoxyalkyl anion from an aromatic aldehyde for use in asymmetric synthesis. The reaction between aromatic aldehydes and aryl or allyl electrophiles with a silylboronate utilizing a chiral copper−N-heterocyclic carbene catalyst and a palladium−bisphosphine catalyst in a synergistic manner occurred with high enantioselectivities to deliver the three-component coupling products, chiral silyl-protected secondary alcohol derivatives. Our method features the catalytic generation of enantioenriched chiral αalkoxyalkylcopper(I) intermediates from aldehydes and their subsequent palladium-catalyzed stereospecific crosscoupling.
The first Csp3-Csp2 cross-coupling using aldehydes as latent α-alkoxyalkyl anion equivalents has been achieved. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes and aryl bromides with a silylboronate afforded the three-component coupling products, silyl-protected benzhydrol derivatives. The reaction pathway involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(i) species followed by its palladium-catalyzed cross-coupling with aryl bromides.
Upon exposure to a catalytic amount of [RhCl(CO) ] in 1,4-dioxane, homopropargylallene-alkynes underwent a novel cycloisomerization accompanied by the migration of the alkyne moiety of the homopropargyl functional group to produce six/five/five tricyclic compounds in good yields. A plausible mechanism was proposed on the basis of an experiment with C-labeled substrate. The resulting tricyclic derivatives were further converted into the corresponding bicyclo[3.3.0] skeletons with vicinal cis dihydroxy groups.
A convenient
asymmetric reductive amination of benzylic ketones
(α-arylated ketones) catalyzed by newly designed Cp*Ir complexes
bearing a chiral N-(2-picolyl)sulfonamidato ligand
was developed. Using readily available β-amino alcohols as chiral
aminating agents, a range of benzo-fused and acyclic ketones were
successfully reduced with formic acid in methanol at 40 °C to
afford amines with favorable chemo- and diastereoselectivities. The
amino alcohol-derived chiral auxiliary was easily removed by mild
periodic oxidants, leading to optically active primary β-arylamines
without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering
the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000,
and the amination could be performed on a large scale exceeding 100
g. The precise hydride transfer to iminium species generated from
the ketonic substrate and the chiral amine counterpart was suggested
by the mechanistic studies on stoichiometric reactions of isolable
hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.
The KHMDS-catalyzed tertiary alkylation of aldehydes, ketones or imines using tertiary benzylic organoboronates is reported. This protocol permitted the use of tertiary benzylic alkylboronates as the tertiary alkyl anion for construction of highly congested contiguous sp3 carbon centers. The mild and transition-metal-free reaction conditions are attractive features of the protocol.
The combination of an allenyne with an additional π‐component in the presence of a rhodium(I) catalyst constitutes a new approach for ring closure. In their Communication on page 4707 ff., C. Mukai and co‐workers report a rhodium(I)‐catalyzed cycloisomerization of homopropargylallene‐alkynes into six/five/five tricyclic frameworks that proceeds through migration of the alkyne moiety of the homopropargyl substituent. The cover picture shows the famous “Tsuzumi Gate” of Kanazawa station.
Upon exposure to ac atalytic amount of [RhCl-(CO) 2 ] 2 in 1,4-dioxane,h omopropargylallene-alkynes underwent anovel cycloisomerization accompanied by the migration of the alkyne moiety of the homopropargyl functional group to produce six/five/five tricyclic compounds in good yields.A plausible mechanism was proposed on the basis of an experiment with 13 C-labeled substrate.T he resulting tricyclic derivatives were further converted into the corresponding bicyclo-[3.3.0] skeletons with vicinal cis dihydroxyg roups.Transition-metal-catalyzed cyclization reactions involving CÀH [1] and/or CÀC [2] bond activation steps have emerged as one of the most powerful and straightforward methods in terms of step economy for the construction of complex polycyclic frameworks.O ur recent endeavors in this field focused on the utilization of the inherent properties of the allene functional group [3] in the presence of additional p-components under rhodium catalysis as summarized in Scheme 1. [4,5] These novel rhodium-catalyzed cycloisomerization reactions of allenynes 1 [6] were tentatively surmised to proceed via the initial formation of the plausible rhodabicyclo[4.3.0] intermediates A,w hich should subse-quently collapse through several steps to various types of final products 2-6. [4,7] As af urther utilization of intermediate A,w ee nvisaged that allene-alkyne derivatives 7,with ahomopropargyl group, would produce benzocyclobutene derivatives 8 if it reacted in ap rocess similar to the conversion of 1c into 6 via intermediates A' ' and B (Scheme 2).Our initial study was carried out using 9,with adimethyl group at the allenic position to avoid unfavorable b-hydride elimination. [8] Thus as olution of 9a (R 1 = R 2 = Me) in 1,4dioxane was heated at 80 8 8Ci nt he presence of 10 mol %o f [RhCl(CO) 2 ] 2 .T he reaction reached completion within 10 min to provide the unexpected six/five/five tricyclic compound 10 a (R 1 = R 2 = Me) in 90 %y ield (Table 1, entry 1). Theexpected product 8 could not be detected in the reaction mixture.T hese conditions ([RhCl(CO) 2 ] 2 in 1,4-dioxane at 80 8 8C) were indeed found to be optimal for conversion of 9a into 10 a. [9] Thet wo derivatives 9b and 9c afforded 10 b and 10 c in 89 and 87 %yield, respectively (entries 2and 3). Upon exposure to the optimized reaction conditions,s ubstrates 9d and 9e,with aphenyl group at one of the two alkyne termini, reacted to give 10 d and 10 e in 78 and 85 %yield, respectively Scheme 1. Our previous work:R h I -catalyzed cyclization of allenynes 1.Scheme 2. This study:R h I -catalyzed cyclization of homopropargylallene-alkynes 7. Table 1: [RhCl(CO) 2 ] 2 -catalyzed cycloisomerizationo fhomopropargylallene-alkynes 9. [a] Entry 9 R 1 R 2 Product Yield [%] [b]
Die Kombination eines Allenins …… mit einer zusätzlichen π‐Komponente in Gegenwart eines Rhodium(I)‐Katalysators ermöglicht einen neuartigen Ringschluss. In ihrer Zuschrift auf S. 4797 berichten C. Mukai et al. über die Entwicklung einer Rhodium(I)‐katalysierten Cycloisomerisierung von Homopropargylallen‐substituierten Alkinen zu tricyclischen Gerüsten, die über die Verschiebung der Alkin‐Einheit des Homopropargyl‐Substituenten verläuft. Das Bild zeigt das bekannte Tsuzumi‐Tor am Bahnhof von Kanazawa.
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