Yuki Naganawa

Stereoselective Construction of Seven-Membered Rings with an All-Carbon Quaternary Center by Direct Tiffeneau−Demjanov-type Ring Expansion

Insertion of one methylene unit into the C-C bond of cyclohexanones is a potentially useful, straightforward method for the construction of seven-membered carbocycles. An especially appealing but largely unexplored method in this arena is the nucleophilic addition of diazoalkanes to the Lewis acid-activated cyclohexanones and subsequent ring expansion accompanied by the extrusion of nitrogen (direct Tiffeneau-Demjanov-type ring expansion). Our primary finding is the unprecedented insertion of alpha-alkyldiazoacetates to cyclohexanone and its heteroanalogues, generating seven-membered rings with one all-carbon quaternary center. On the basis of this finding, highly diastereoselective ring expansion of substituted cyclohexanones was developed, furnishing seven-membered rings with 1,4-quaternary-tertiary, 1,4-quaternary-quaternary, or 1,3,5-quaternary-tertiary-tertiary stereogenic centers in a single operation starting from readily available materials. The stereochemical outcome of the product can be easily predicted from the conformation of starting cyclohexanones. Enantioenriched products could be also accessed by the use of (-)-phenylmenthyl alpha-alkyldiazoacetates.

Brønsted acid-catalyzed insertion of aryldiazoacetates to sp2 carbon-CHO bond: facile construction of chiral all-carbon quaternary center.

Aryldiazoacetates could be formally inserted into the carbon−carbon bond of the Bronsted acid-activated aromatic and α,β-unsaturated aldehydes. Use of phenylmenthyl esters allowed the asymmetric induction at the inserted all-carbon quaternary carbon center with the excellent stereoselectivities.

Stereoselective Synthesis of α-Alkyl-β-keto Imides via Asymmetric Redox C−C Bond Formation between α-Alkyl-α-diazocarbonyl Compounds and Aldehydes

Asymmetric redox C-C bond formation between alpha-alkyl-alpha-diazocarbonyl compounds and aldehydes was developed as a practical and general method for the construction of alpha-alkyl-beta-keto imides having a chiral nonracemic tertiary stereogenic center.

Construction of a Chiral Silicon Center by Rhodium-Catalyzed Enantioselective Intramolecular Hydrosilylation.

Rhodium-catalyzed enantioselective desymmetrizing intramolecular hydrosilylation of symmetrically disubstituted hydrosilanes is described. The original axially chiral phenanthroline ligand (S)-BinThro (Binol-derived phenanthroline) was found to work as an effective chiral catalyst for this transformation. A chiral silicon stereogenic center is one of the chiral motifs gaining much attention in asymmetric syntheses and the present protocol provides cyclic five-membered organosilanes incorporating chiral silicon centers with high enantioselectivities (up to 91 % ee). The putative active Rh(I) catalyst takes the form of an N,N,O-tridentate coordination complex, as determined by several complementary experiments.

Asymmetric Induction at Remote Quaternary Centers of Cyclohexadienones by Rhodium-Catalyzed Conjugate Hydrosilylation

The enantioselective desymmetrizing conjugate hydrosilylation of prochiral differently γ,γ-disubstituted cyclohexadienone derivatives 2 to furnish the corresponding cyclohexenones 4 with a remote chiral all-carbon quaternary center at the γ position is described. Chiral rhodium-bis(oxazolinyl)phenyl complexes 1 were effective catalysts for this transformation. This catalytic system was extended to the asymmetric transformation of spirocarbocyclic cyclohexadienones 5 to give the corresponding products 6 with high enantiomeric ratios.

Reactions Triggered by Lewis Acidic Organoaluminum Species

The use of organoaluminum-based Lewis acids (AlRnX3–n; R 1⁄4 alkyl, alkynyl, X 1⁄4 halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on: (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C–X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels–Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions).

Construction of stereodefined 1,1,2,2-tetrasubstituted cyclopropanes by acid catalyzed reaction of aryldiazoacetates and α-substituted acroleins

Michael-initiated ring closure of aryldiazoacetates and alpha-substituted acroleins under acid catalysis offers a unique opportunity for the stereoselective formation of various tetrasubstituted cyclopropanes.