Semipinacol Rearrangement Research Articles

Synthesis of the C1–C17 Segment of Bafilomycin N

The C1–C17 segment of bafilomycin N has been synthesized. The C1–C11 segment was synthesized by the anti-selective vinylogous Mukaiyama aldol reaction with a chiral vinylketene silyl N,O-acetal and the Horner–Wadsworth–Emmons reaction, whereas C12–C17 was constructed by the syn-selective vinylogous Mukaiyama aldol reaction and the Jung’s semipinacol rearrangement. Those segments were connected by the Stille coupling to afford the C1–C17 segment.

Synthesis of 2-(2-Oxo-2-phenylethyl)cyclopentanone by Rhodium-Catalyzed Tandem Alkynyl Cyclobutanols Hydroacylation and Semipinacol Rearrangement.

A rhodium-catalyzed tandem reaction of alkynyl cyclobutanols with salicylaldehydes has been developed. The reaction offers a new and atom-economical approach for the selective preparation of multisubstituted 2-(2-oxo-2-phenylethyl)cyclopentanone in high yields under mild reaction conditions with tolerance of a broad range of substituted alkynyl cyclobutanols and salicylaldehyes. The isolation of intermediate suggests that the reaction proceeds through a sequential process of intermolecular hydroacylation and semipinacol rearrangement.

Deciphering the exceptional selectivity of semipinacol rearrangements in cis-fused β-lactam diols using high-level quantum chemical methods

The semipinacol rearrangement mechanism in cis-fused β-lactam diols has been found to kinetically and thermodynamically favor acyl migration. The semipinacol rearrangement was also investigated for trans-fused β-lactam diol, in which the reversed selectivity that favors the alkyl migration was observed.

Photoredox-catalyzed sulfonylation of alkenylcyclobutanols with the insertion of sulfur dioxide through semipinacol rearrangement

A photoredox-catalyzed sulfonylation of alkenylcyclobutanols with the insertion of sulfur dioxide through semipinacol rearrangement under visible light irradiation is developed.

Sonochemically assisted 2,3-dideoxygenation and skeletal rearrangement of ecdysteroid derivatives

Sonochemical 2,3-dideoxygenation of ecdysteroids with the Δ 2(3)-bond generation and activation of the C–C bonds of the steroid core in the poststerone derivatives, that causes the skeletal rearrangement have been carried out for the first time. Thus, the ultrasonically assisted reaction of 2,3-dimesyloxy derivatives of ecdysteroids with the NaI-Zn-DMF system gives rise to their 2,3-dideoxy-Δ2(3)-analogues with yields 70–92%. In the case of 2,3-dimesyloxypoststerone as the initial ecdysteroid substrate the reaction is accompanied by the activation of the allyl moiety and semipinacol rearrangement, resulting in the C13–C14 bond migration with C/D rings contraction/expansion and providing novel short chain (8R)-13(14 → 8)-abeo-isomer.

Catalytic Radical-Polar Crossover Reactions of Allylic Alcohols.

Radical-polar crossover hydrofunctionalizations of tertiary allylic alcohols are described. Depending on the structure of the catalyst, corresponding epoxides or semipinacol rearrangement products are selectively obtained in good yields. Experimental evidence points to the participation of alkylcobalt complexes as electrophilic intermediates.

A Facile Approach to Oximes and Ethers by a Tandem NO+ -Initiated Semipinacol Rearrangement and H-Elimination.

An efficient oximation method has been developed on the basis of NO+ -initiated semipinacol rearrangement and subsequent proton elimination. The procedure enabled the rapid construction of a series of oximes and oxime ethers with spiro quaternary stereocenters from allylic silyl ethers. Additional features of this reaction include wide substrate tolerance as well as the commercial availability of the safe nitrosation reagent NOBF4 . The key N-heterotricyclic cores of three natural alkaloids, tuberostemoninol B, (+)-quebrachidine, and an insecticide, were also constructed efficiently by this method.

A Facile Approach to Oximes and Ethers by a Tandem NO+‐Initiated Semipinacol Rearrangement and H‐Elimination

AbstractAn efficient oximation method has been developed on the basis of NO+‐initiated semipinacol rearrangement and subsequent proton elimination. The procedure enabled the rapid construction of a series of oximes and oxime ethers with spiro quaternary stereocenters from allylic silyl ethers. Additional features of this reaction include wide substrate tolerance as well as the commercial availability of the safe nitrosation reagent NOBF4. The key N‐heterotricyclic cores of three natural alkaloids, tuberostemoninol B, (+)‐quebrachidine, and an insecticide, were also constructed efficiently by this method.

Borinic Acid/Halide Co-catalyzed Semipinacol Rearrangements of 2,3-Epoxy Alcohols.

A new mode of catalysis of the semipinacol rearrangement of 2,3-epoxy alcohols is described. In combination with a halide salt additive, diarylborinic acids promote a Type II rearrangement that occurs with net retention of configuration. This unusual stereochemical outcome is consistent with a mechanism involving regioselective ring opening of the epoxy alcohol by halide, followed by rearrangement of the resulting halohydrin-derived borinic ester. The protocol is applicable to a range of substrates, enabling ring contractions and expansions as well as stereospecific syntheses of acyclic β-hydroxycarbonyl compounds.

Organocatalytic Asymmetric Cascade Aerobic Oxidation and Semipinacol Rearrangement Reaction: A Visible Light-Induced Approach to Access Chiral 2,2-Disubstituted Indolin-3-ones.

An enantioselective cascade aerobic oxidation and semipinacol rearrangement reaction of 2-aryl-3-alkyl-substituted indoles via visible-light-driven cooperative organophotoredox and H-bonding catalysis is reported. The current method provides an expedient and sustainable approach to furnish a variety of valuable chiral 2-aryl-2-alkyl-substituted indolin-3-ones in 64-90 % yield with 58-94 % ee. Preliminary control experiments present important insights into the stereochemistry.

Recent Advances in the Synthesis of β-Functionalized Ketones by Radical-Mediated 1,2-Rearrangement of Allylic Alcohols.

β-Functionalized ketones are a highly important and valuable class of compounds that have gained increasing attention from organic chemists due to their intensive uses as versatile synthetic intermediates and building blocks in complex molecule assembly and natural product synthesis. Accordingly, there is continuing interest in the development of new approaches for the synthesis of β-functionalized ketones. In recent years, radical-mediated 1,2-rearrangement reactions of allylic alcohols, which proceed through cationic (semipinacol) rearrangements or radical (neophyl) rearrangements, have presented an attractive and powerful strategy to access various diversely β-functionalized ketones. Interestingly, this strategy allows for the direct installation of a variety of valuable functional groups at the β-position of cyclic and acyclic ketones by employing different radical precursors. However, a review focusing on the preparation of β-functionalized ketones by radical-mediated 1,2-rearrangement reactions of allylic alcohols has not been summarized to date. This Minireview highlights recent progress made in this highly active and interesting research area, and the corresponding mechanisms will also be discussed.

Stereocontrolled Construction of ABCD Tetracyclic Ring System with Vicinal All-Carbon Quaternary Stereogenic Centers of Calyciphylline A Type Alkaloids.

A unique approach to the synthesis of an ABCD tetracyclic core bearing the vicinal all-carbon quaternary stereogenic centers of the calyciphylline A type alkaloids is reported. The synthesis features two C-C bond formations at a sterically congested position: one is an intramolecular pinacol coupling to construct the central A ring; the other is a semipinacol rearrangement to construct a quaternary stereogenic center adjacent to another quaternary center.

Intramolecular Hydrogen Bonding in α-Epoxy Alcohols: A Conformational Analysis of 1,2-Dialkyl-2,3-epoxycyclopentanol Diastereomers

Geometry optimizations for 11 1,2-disubstituted-2,3-epoxycyclopentanol diastereomers were studied using the M06-2X/cc-pVTZ method and basis set to probe mechanistic details in the α-epoxy alcohol semipinacol rearrangement reaction. Computations show that the electronic energies of active cis diastereomers are lower than those of the corresponding trans diastereomers by an average of 0.9 kcal mol–1. Intramolecular hydrogen bonding stabilizes the cis substrate energy by 3.4 kcal mol–1, on average. These results provide the first evidence into an intramolecular H-atom transfer as the α-epoxy alcohol converts into the corresponding 2,2-disubstituted-1,3-ketol.

A catalytic allylic cation-induced intermolecular allylation-semipinacol rearrangement.

A catalytic intermolecular semipinacol rearrangement induced by allylic carbocations has been realized. This tandem reaction is highly efficient under the catalysis of ZnBr2, generating a wide range of α-homoallyl substituted ketones which contain all-carbon quaternary centres in good to excellent yields (up to 98%) with moderate to high diastereoselectivities (up to >20 : 1). Synthetic application of this novel methodology in the construction of core structures of natural products is also reported.

Optimization of Manganese Coupling Reaction for Kilogram-Scale Preparation of Two Aryl-1,3-dione Building Blocks

Aryl-1,3-diones represent a promising new class of herbicidal acetyl-CoA carboxylase (ACCase) inhibitors. The original synthesis of this structural motif employed in the research phase involved a selenium oxide mediated oxidation, the use of diazoacetate and aryl lead reagents, and a low temperature oxidation of an aryl lithium intermediate, so it was not well suited to large scale synthesis. For kilogram scale synthesis of the two aryl-1,3-dione building blocks (3 and 4), we developed an alternative route which employs a manganese or manganese–copper catalyzed alkyl Grignard coupling and a semi-pinacol rearrangement of an epoxide as the key steps. The optimized conditions could be of general interest as scalable methods for the synthesis of 2-alkyl substituted benzaldehydes and of 2-aryl-1,3-diones.

Copper-Catalyzed Enantioselective Domino Arylation/Semipinacol Rearrangement of Allylic Alcohols with Diaryliodonium Salts.

A copper-catalyzed enantioselective arylative semipinacol rearrangement of allylic alcohols was developed. In the presence of a catalytic amount of an in situ generated chiral copper-bisoxazoline complex, reaction of allylic alcohols with diaryliodonium salts afforded spirocycloalkanones in high yields with high diastereo- and enantioselectivities. A two-point binding model engaging the carbon-carbon double bond and the proximal hydroxyl group was proposed to be responsible for the highly efficient chirality transfer.

Enantioselective Copper-Catalyzed Arylation-Driven Semipinacol Rearrangement of Tertiary Allylic Alcohols with Diaryliodonium Salts.

A copper-catalyzed enantioselective arylative semipinacol rearrangement of allylic alcohols using diaryliodonium salts is reported. Chiral Cu(II)-bisoxazoline catalysts initiate an electrophilic alkene arylation, triggering a 1,2-alkyl migration to afford a range of nonracemic spirocyclic ketones with high yields, diastereo- and enantioselectivities.

Semipinacol and protoadamantane-adamantane rearrangements of 5,6-dibromoadamantan-2-one and -2-ol

A number of new polybrominated adamantanes were formed by rearrangements and bromination of 2,2,6,6-tetrabromoadamantane under Friedel-Crafts conditions. Protoadamantane-4,10-dione, 10-acetoxyprotoadamantan-4-one, 1,2,6-triacetoxyadamantane and 5,6-diacetoxyadamantan-2-one were formed by successive semipinacol and protoadamantane-adamantane rearrangements of 5,6-dibromoadamantan-2-one and 5,6-dibromoadamantan-2-ol. This work may open up new pathways for the synthesis of 1,2,6-trisubstituted adamantanes.

Synthesis of Macrocyclic Ketones through Catalyst-Free Electrophilic Halogen-Mediated Semipinacol Rearrangement: Application to the Total Synthesis of (±)-Muscone.

A series of macrocycles were successfully prepared using electrophilic halogen-mediated semipinacol rearrangement under mild conditions. Although the expansion from small ring to medium ring is an energetically unfavorable process, the electrophilic halogenation was found to be powerful enough to override such an energy barrier. The rearranged products could further undergo Dowd-Beckwith rearrangement to give the corresponding one-carbon ring-expanded ketones. This approach has been applied to the total synthesis of the natural product (±)-muscone, which is widely used in modern perfumery and medicines, in a two-step sequence.

Ring strain-dictated divergent fluorinating Prins cyclization or semipinacol rearrangement.

We have developed ring-strain dictated divergent diastereoselective fluorinating Prins cyclization reactions or semipinacol rearrangement reactions to access tetrahydropyrans containing a fluorohydrin or a carbonyl moiety at quaternary carbon centers under mild conditions, respectively.