Specific and Strong Acceleration of Nitrosation by Nitrosyl Sulfonates Using the Bis-Coordinating Lewis Acid TiCl4 or SnCl4.

Nitrosyl triflate is an excellent donor of NO+ to C═C and very unreactive benzenoids, in contrast to the much less reactive nitrosyl mesylate. However, both of these reagents are strongly activated by the bis-coordinating Lewis acids TiCl4 and SnCl4 and become super reactive NO+ donors. Strong catalysis and activation are even observed with the inherently less electrophilic nitrosyl trifluoroacetate. Monocoordinating strong Lewis acids, e.g., MeAlCl2, are relatively ineffective.

Synthetically Useful Transformations of Olefins via Cationic 1,2-Oxazetium Intermediates.

Nitrosyl triflate serves as a NO+ donor in reactions with many olefinic substrates to form reactive, cationic 1,2-oxazetium cycloadducts that can be converted selectively into a wide range of useful products depending on reagents and conditions.

Synthesis of Tetracyclic C2-Symmetric Ketiminium Salts and Evaluation as Catalysts for Epoxidation.

Short synthetic routes to the nonplanar tetracyclic ketiminium salt A and two close analogs are described. These are helical nonplanar structures as shown by X-ray crystallography.

Two Unprecedented Reactions of Nitrosyl Triflate: NO+-Induced Cationic Cascade Cyclization and C═C Oxidative Cleavage.

Nitrosyl triflate is shown to react with olefins in a CH2Cl2 solution by three different pathways depending on structure and reaction conditions: (1) cationic cyclization, (2) C═C cleavage, and (3) allylic nitrosation. Possible reaction pathways are described.

Mechanism of the Reaction of Olefins with Nitrous Anhydride (O═N-O-N═O) to Form 1,2-Oxazetes.

The mechanistic pathway for the formation of 1,2-oxazetes by reaction of olefins with nitrous anhydride has been clarified. The initial reaction intermediate, a ß-nitroso nitrite ester that is sensitive to light, undergoes O-NO fission to form a ß-nitroso alkoxy radical, even with ambient fluorescent lighting but much faster with blue light irradiation. The oxygen of the alkoxy radical subsequently adds to the adjacent nitroso group to generate a cyclic four-membered nitrosyl radical. The 1,2-oxazete is then produced by elimination to generate the C═N bond. No 1,2-oxazete formation occurs in the dark.

Nitrosyl Triflate and Nitrous Anhydride, Same Mode of Generation, but Very Different Reaction Pathways. Direct Synthesis of 1,2-Oxazetes, Nitroso or Bisoxazo Compounds from Olefins.

Nitrosyl triflate (TfONO) can be generated in situ from tetra-n-butylammonium nitrite and triflic anhydride (1:1) in CH2Cl2 solution at ca. -30 °C. It acts as a powerful and soluble nitrosating agent with a wide range of olefinic or aromatic substrates. Nitrous anhydride (O═N-O-N═O) can be generated in the same way using tetra-n-butylammonium nitrite and triflic anhydride (2:1) in CH2Cl2 solution at ca. -30 °C. Each reagent has been isolated and characterized. They react with olefins to give different products. Nitrosyl triflate is an excellent reagent for generating either vinylic or allylic nitroso compounds or their dimeric bisoxazo derivates. Nitrous anhydride efficiently converts many olefins to 1,2-oxazetes in a single step, making this class of compounds readily available from olefins for the first time. We have also discovered another route to 1,2-oxazetes involving a novel rearrangement/isomerization of allylic nitroso compounds which is catalyzed by Pd-C/H2.

Contrasting Diastereoselectivity between Cyclic Nitrones and Azomethine Ylides. Stereocontrolled Pathways to cis-anti-anti-cis-Oxazatetraquinanes from a Bicyclic Nitrone.

A study of [3 + 2] cycloaddition reactions of a bicyclic nitrone with various cyclopentenes has clarified the diastereomeric preferences as a function of the olefinic structure. It has also identified an important stereochemical difference between nitrones and the analogous azomethine ylides in [3 + 2] cycloaddition reactions.

A Useful Method for the Conversion of Olefins to Nitro Olefins.

Triflyl nitrate is easily generated from tetra-n-butylammonium nitrate in CH2Cl2 solution and serves as an effective nitrating agent for a wide range of unsaturated substrates to form nitro olefins.

Unraveling the C2-Symmetric Azatetraquinane System. Simple, Enantioselective Syntheses.

Concise stereocontrolled synthetic routes to the C2-symmetric azatetraquinane 1 (or, also, the enantiomer) are described. The successful execution of the synthesis involved innovation in the methodology for [3+2] cycloaddition and stereochemical control.

CuBr2-catalyzed diastereoselective allylation: total synthesis of decytospolides A and B and their C6-epimers.

An efficient CuBr2-catalyzed diastereoselective allylation of a cyclic hemiacetal with allyltrimethylsilane as a nucleophile has been developed. The protocol offers a cost effective, protecting group tolerant, and operationally simple approach to 2,6-trans-disubstituted tetrahydropyran with excellent diastereoselectivity. Furthermore, the application of this methodology has been demonstrated in the total synthesis of decytospolides A and B and their C6-epimers.

Total synthesis and stereochemical revision of relgro and 10'-oxorelgro.

The first asymmetric total synthesis and stereochemical assignments of 10-membered macrolactones relgro and 10'-oxorelgro are disclosed. To this end, palladium-catalyzed Stille coupling, the Mitsunobu reaction, ring-closing metathesis, EDCI promoted coupling and the Jacobsen hydrolytic kinetic resolution are used as key steps. The total synthesis followed by thorough evaluation of the optical rotation and CD spectral data led to the revision of the absolute configuration at C-6' for both relgro and 10'-oxorelgro. Moreover, the 1H as well as 13C NMR data are reported for the first time for relgro.

Total Synthesis of Four Isomers of the Proposed Structures of Cryptorigidifoliol K.

The first asymmetric convergent total synthesis of four isomers of proposed structures of cryptorigidifoliol K (1a, 1b, 1c, and 1d) has been achieved from commercially available starting materials. The key steps in this synthesis involve tandem isomerization followed by a C-O and C-C bond-forming reaction for the construction of trans-2,6-disubstituted dihydropyran, iodolactonization, isomerization of terminal alkene, and cross-metathesis reaction. The large discrepancies in the spectroscopic data (1H NMR) of synthetic cryptorigidifoliol K from the natural product suggest that the structure of the natural cryptorigidifoliol K requires revision.

Gold(I)-Catalyzed Cyclization for the Synthesis of 8-Hydroxy-3- substituted Isocoumarins: Total Synthesis of Exserolide F.

A highly regioselective gold(I)-catalyzed 6-endo-dig cyclization of 2,2-dimethyl-5-(alkynyl)-4H-benzo[d][1,3]dioxin-4-ones for the synthesis of 8-hydroxy-3-substituted isocoumarins is described. Key features of the reaction include the broad substrate scope, scalability, and tolerance for protecting groups. The synthetic utility of this novel method is demonstrated by the first total synthesis of exserolide F, an isocoumarin-containing polyol natural product.

First asymmetric total synthesis of aspergillide D.

The first asymmetric total synthesis of a 16-membered macrolide, aspergillide D, is described. The chiral centers of the acid are derived from d-ribose and the alcohol subunit from 1,8-octane diol through Sharpless kinetic resolution, respectively. The other key reactions include Yamaguchi esterification, ring-closing metathesis reaction, and Shiina macrolactonization to construct the fully functionalized macrocycle.

Total Synthesis of Tetraketide and Cryptorigidifoliol I via a Sequential Allylation Strategy.

A unified and efficient synthetic route for both tetraketide (1) and cryptorigidifoliol I (2) has been devised successfully from commercially available starting materials in 11 and 17 steps, with 16% and 11% overall yields, respectively. Highlights of the syntheses involved sequential Lewis acid-catalyzed highly regio- and diastereoselective allylations and intramolecular Mitsunobu lactonization.