Catalyzed olefin isomerization leading to highly stereoselective Claisen rearrangements of aliphatic allyl vinyl ethers

Iridium(I)-catalyzed olefin isomerization in bis(allyl) ethers is integrated into a generally applicable strategy for affecting highly stereoselective Claisen rearrangements. Catalyzed alkene isomerization affords allyl vinyl ethers from easily prepared di(allyl) ethers; direct thermolysis of these reaction mixtures leads to highly diastereoselective [3,3] sigmatropic rearrangements affording syn-2,3-dialkyl-4-pentenal derivatives. An easily executed strategy for realizing asymmetric variants of the isomerization-Claisen rearrangement (ICR) reactions is also described.     

Strategies for expanding structural diversity available from olefin isomerization-claisen rearrangement reactions

Boron-substituted di(allyl) ethers provide an efficient conduit for expanding the structural diversity available from olefin isomerization-Claisen rearrangement (ICR) reactions. Easily prepared allyl propargyl ethers undergo chemoselective Zr(IV)-catalyzed hydroboration to afford the boron-substituted ICR substrates. The boron-substituted allyl residue undergoes chemoselective Ir(I)-catalyzed olefin isomerization and in situ Claisen rearrangement to afford stereodefined beta-boryl aldehyde products. Functionalization of the C-B linkage by oxidation or Suzuki cross-coupling provides a route to Claisen adducts previously inaccessible from the ICR methodology.     

Stereoselective Construction of Tertiary Homoallyl Alcohols and Ethers by Nucleophilic Substitution at Quaternary Carbon Stereocenters

An efficient method for the stereoselective construction of tertiary C−O bonds via a stereoinvertive nucleophilic substitution at the quaternary carbon stereocenter of cyclopropyl carbinol derivatives using water, alcohols and phenols as nucleophiles has been developed. This substitution reaction proceeds under mild conditions and tolerates several functional groups, providing a new access to the stereoselective formation of highly congested tertiary homoallyl alcohols and ethers.     

Studies toward the total synthesis of armatol F: stereoselective construction of the C6 and C7 stereocenters and formation of the A-ring skeleton

Armatol F, isolated from the red alga Chondria armata as a polyether triterpene, has a solitary oxepane (A-ring) and a fused tricyclic ether moiety (BCD-ring). The A-ring features a rare cis-relationship between the hydroxy group at the quaternary carbon C6 and the carbon chain at C7. As part of our program toward the total synthesis of armatol F, a new stereoselective method for the construction of the C6 and C7 stereocenters has been developed based on chirality-transferring Ireland-Claisen rearrangement. The A-ring skeleton has also been synthesized from the rearrangement product by a process including ring-closing olefin metathesis.     

Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes

The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo‐ and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter.     

Lewis acid promoted highly stereoselective rearrangement of 2,3-aziridino alcohols: a new efficient approach to beta-amino carbonyl compounds

A new Lewis acid promoted rearrangement reaction of 2,3-aziridino alcohols was discovered, which involved the highly stereoselective construction of a diastereogenic quaternary carbon center and efficient formation of beta-amino carbonyl compounds in excellent yields. A wide variety of Lewis acids were proved to be effective for the reaction, and a possible reaction mechanism was also discussed.     

Total synthesis of (-)-amathaspiramide F

The stereoselective total synthesis of the marine alkaloid (-)-amathaspiramide F (1) was achieved from the alpha-hydoxy-alpha-ethynylsilane 2. The crucial steps in this synthesis involved not only the enolate Claisen rearrangement of the alpha-acyloxy-alpha-alkenylsilane 6 for the construction of the nitrogen-containing quaternary carbon center, but also the chemoselective formation of the azaspirohemiaminal 12 using heptamethyldisilazane as the methylamine equivalent and the regioselective dibromination of the phenol moiety of 12 using n-Bu(4)NBrCl(2).     

A new entry to Amaryllidaceae alkaloids from carbohydrates: total synthesis of (+)-vittatine

The stereoselective and chiral synthesis of the Amaryllidaceae alkaloid, (+)-vittatine 1, is described; the quaternary carbon in 1 was generated by Claisen rearrangement of a cyclohexenol derived from D-glucose by way of a Ferrier's carbocyclisation reaction and a hexahydroindole skeleton was effectively constructed by intramolecular aminomercuration-demercuration, followed by Chugaev reaction.     

Stereoselective synthesis of the right-hand segment of tubiferal A

Tubiferal A, a triterpenoid isolated from myxomycete Tubifera dimorphotheca, exhibits a reversal effect of vincristine (VCR) resistance against VCR-resistant KB cell lines. The compound possesses a complex structure involving the 6-7-6-5 polycyclic carbon framework with various functional groups. The stereoselective synthesis of the right-hand segment of tubiferal A was achieved on the basis of the cyclopentene annulation method and the semi-pinacol rearrangement reaction of an epoxy alcohol for constructing the trans-fused 6-5 bicyclic skeleton possessing two quaternary carbon atoms at the angular positions.     

Stereocontrolled synthesis of substituted bicyclic ethers through oxy-Favorskii rearrangement: total synthesis of (±)-communiol E

The potential of the oxy-Favorskii rearrangement to form branched cis-fused bicyclic ethers was explored. Both tertiary and quaternary centers were constructed in highly stereospecific manners. Methanol and primary amines were effective nucleophiles for the rearrangement. The total synthesis of (±)-communiol E was achieved based on this method.     

Imino 1,2-Wittig rearrangement of hydroximates and its application to synthesis of cytoxazone

The imino 1,2-Wittig rearrangement of hydroximates provides a novel method for the construction of 2-hydroxyoxime ethers. Upon treatment with LDA, Z-hydroximates smoothly underwent stereoselective rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into amino alcohols. On the other hand, the rearrangement of E-hydroximates gave a mixture of E- and Z-2-hydroxyoxime ethers. This method was successfully applied to a practical synthesis of cytoxazone.     

Brook Rearrangement as a Trigger for the Ring Opening of Strained Carbocycles

The combined regio‐ and stereoselective carbometalation of cyclopropenyl amides, followed by the addition of an acyl silane, led to the formation of polysubstituted cyclopropyl derivatives as unique diastereoisomers. Upon warming of the reaction mixture to room temperature, a Brook rearrangement proceeded with inversion of configuration to provide ready access to δ‐ketoamides possessing a quaternary carbon center with high enantiomeric ratios through selective C? C bond cleavage of the ring.     

Progressive studies on the novel samarium-catalyzed diastereoselective tandem semipinacol rearrangement/Tishchenko reduction of secondary alpha-hydroxy epoxides

A novel and highly diastereoselective samarium-catalyzed tandem rearrangement/reduction of secondary alpha-hydroxy epoxides, which involves a C1 to C3 carbon migration rearrangement and a very interesting hetero-Tishchenko reduction of the intermediate aldehyde and the reductant aldehyde, has been reported. This reaction could be developed to provide a facile and stereoselective construction of 2-quarternary 1,3-diol units with an hydroxymethyl moiety attached to the diastereogenic quaternary carbon center. Detailed investigations have been carried out concerning the screening of the aldehydes as a reductant, the optimization of reaction conditions, and the substrate scope of this tandem reaction. A catalytic cycle for this reaction, the electronic and steric effects of the reductant aldehydes, and the mechanism for the acyl migration of 1,3-diol monoesters are proposed.     

Addition of TMS-substituted oxiranyl anions to acylsilanes. A highly stereoselective approach to tetrasubstituted (Z)-β-hydroxy-α-TMS silyl enol ethers

A highly stereoselective approach to novel tetrasubstituted (Z)-β-hydroxy-α-TMS silyl enol ethers is described. The reaction proceeds via a sequential addition/[1,2]-Brook rearrangement/epoxide-opening process of TMS-substituted oxiranyl anions with acylsilanes.     

Carbanion-accelerated Claisen rearrangements 3. Vicinal quaternary centers

The preparation and Claisen rearrangement of highly substituted allyl vinyl ethers is described. It is demonstrated that the thermal and anionic versions of the Claisen rearrangement are capable of creating vicinal quaternary centers.     

Asymmetric synthesis of alpha-substituted aldehydes by Pd-catalyzed asymmetric allylic alkylation-alkene isomerization-Claisen rearrangement

[Structure: see text] Enantiospecific aliphatic Claisen rearrangement was realized with generally high chirality transfer. The requisite substrates were synthesized via Pd-catalyzed asymmetric allylic alkylation (AAA) from easily obtained starting materials. After protection, the resultant bisallyl ethers underwent olefin isomerization and in situ Claisen rearrangement (ICR) to generate alpha-chiral aldehydes. Remarkable chemoselectivity in the olefin isomerization step was observed. An asymmetric synthesis of communiol A was accomplished applying this methodology.     

Expedient synthesis of highly substituted pyrroles via tandem rearrangement of α-diazo oxime ethers

An efficient rhodium-catalyzed synthesis of 2H-azirines and pyrroles has been developed. Novel rearrangement of α-oximino ketenes derived from α-diazo oxime ethers provides 2H-azirines bearing quaternary centers and allows for subsequent rearrangement to highly substituted pyrroles in excellent yields.     

A highly stereoselective approach to tetrasubstituted (E)-β-hydroxy silyl enol ethers by addition of aryl-substituted oxiranyl anions to acylsilanes

A highly stereoselective approach to tetrasubstituted (E)-β-hydroxy silyl enol ethers is described. The reaction proceeds via a sequential addition/[1,2]-Brook rearrangement/epoxide-opening process of aryl-substituted oxiranyl anions with acylsilanes.     

Spiroketals via oxidative rearrangement of enol ethers

Oxidative rearrangement of cyclic enol ethers leads to alpha-alkoxyesters. In the presence of a neighboring spiroether, this approach provides a stereoselective access to spiroketals. A modified proposal for the biosynthesis of acutumine is presented.     

Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids using (S,S)-cyclohexane-1,2-diol as a chiral auxiliary

Diastereoselective alkylation of ethyl 2-methyl- and/or 2-ethylacetoacetates using the (S,S)-cyclohexane-1,2-diol as an acetal chiral auxiliary afforded enol ethers (2a-f and 5a-f) of 92->95% de in 31-70% yields. Removal of the cyclohexane-1,2-diol with BF(3)-OEt(2) afforded beta-keto esters (3 and 6) bearing a chiral quaternary carbon. The beta-keto esters could be easily converted into optically active alpha-methylated and/or alpha-ethylated alpha,alpha-disubstituted amino acids (12 and 13) in 21-99% yields using Schmidt rearrangement.