Publications and Patent Applications

Reductive Cleavage of Aryl O-Carbamates to Phenols by the Schwartz Reagent. Expedient Link to the Directed Ortho Metalation Strategy.Morin J, Zhao Y, Snieckus V. Org Lett. Aug 2013

A general, mild, and efficient method for the reductive cleavage of aryl O-carbamates to phenols, 1 → 2 using the Schwartz reagent is reported. The method is selective, tolerating a large number of functional groups; may be carried out by direct or by an economical in situ procedure; and, notably, establishes a synthetic connection to the directed ortho metalation strategy allowing new entries into difficult to prepare contiguously substituted aromatics and heteroaromatics.

C-H Activation versus Directed ortho Metalation (DoM): Complementary Borylation of Aromatics and Heteroaromatics, Hurst, T.E., Macklin, T., Hartmann, E., Kügel, W., Parisienne-La Salle, J., Becker, M., Marder, T. and Snieckus, V., Chem. –Eur. J., 20

Systematic studies are presented demonstrating the complementarity of directed ortho metalation (DoM) and Ir-catalyzed strategies for the provision of borylated aromatics and their subsequent Suzuki–Miyaura coupling reactions. A new concept, the use of the TMS group, readily introduced by DoM, as a latent regiodirective moiety to overcome the otherwise problematic production of isomeric borylated product mixtures is presented. Additional electrophile-induced ipso-deborylation and DoM reactions of the Bpin products are described.

A Directed ortho Metalation (DoM) – Halogen Dance Strategy for the Construction of Polysubstituted Aromatics and Pyridines. The Halogen Dance – Anionic ortho Fries Rearrangement, Miller, R.E., Rantanen, T., Ogilvie, K.A., Groth, U., Snieckus, V., Org. L

A general and efficient directed ortho metalation (DoM)-halogen dance (HD)-electrophile quench sequence for the synthesis of trisubstituted pyridyl O-carbamates is described. A second HD sequence furnishes highly functionalized tetrasubstituted pyridines. Furthermore, a hitherto unobserved double HD rearrangement is reported. Under similar LDA conditions, aromatic O-carbamates with OMe, Cl, and F substituents (4a-c) undergo either a HD-electrophile quench sequence, 4a-c --> 18-20, or a HD-anionic ortho Fries rearrangement, 4a-c --> 6a-c, respectively

Copper Catalyzed Cross Coupling Interrupted by an Opportunistic Smiles Rearrangement: An Efficient Domino Approach to Dibenzoxazepinones, Kitching, M.O., Hurst, T.E., Snieckus, V., Angew. Chem. Int. Ed., 2011, submitted.

Unexpected Smiles! An unusual and highly regioselective synthesis of dibenzoxazepinones by a domino sequence assisted by an unexpected Smiles rearrangement is reported. The process is effective on electronically differentiated phenols and shows a high tolerance to variation in the benzamide substituents. A plausible path for the reaction, supported by preliminary mechanistic data, is offered.

In Situ Anionic Shielding for Regioselective Metalation: Directed peri and Iterative Metalation Routes to Polyfunctionalized 7-Azaindoles, Schneider, C., David, E., Toutov, A., Snieckus, V., Angew. Chem. Int. Ed., 2012, 2722–2726.

Strolling the ring: A general regioselective directed peri(C4)-metalation route to 1 through an in situ N-anionic protection of C2 is reported. The azaindoles may be elaborated by directed ortho metalation (DoM) and Suzuki coupling to more complex heterocyclic systems. An iterative ring-walk DoM sequence furnishes the exhaustively substituted 2. DMG=directed metalation group, TMEDA=N,N,N′,N′-tetramethylethylenediamine, TMS=trimethylsilyl.

Directed ortho-Metalation–Cross-Coupling Strategies. One-Pot Suzuki Reaction to Biaryl and Heterobiaryl Sulfonamides, Cedric Schneider, Broda, E. and Snieckus, V. Org. Lett., 2011, 13, 3588–3591.

A general synthesis of stable ortho-boropinacolato aryl and heteroaryl sulfonamides by directed ortho-metalation (DoM) and either MeOBPin or i-PrOBpin electrophile quench, 3 f 4, is described. A one-pot metalation␣Suzuki cross-coupling procedure for the synthesis of biaryls and heterobiaryls, 3 f 5, and a complementary DoM␣Ir-catalyzed boronation sequence (Scheme 6) are delineated.

Schwarz Reagents: Methods of In Situ Generation US 2010 0145060 A1

Embodiments of the invention provide a method of using Schwartz Reagent, Cp2Zr(H)Cl, without accumulating or isolating it. Methods provide mixtures of Cp2ZrCl2, reductants that selectively reduce Cp2ZrCl2, and substrates. After reaction of Cp2ZrCl2 and the reductant, an intermediate reduction product is formed, apparently Schwartz Reagent. The in situ Schwartz Reagent then selectively reduces certain functional groups on the substrate. Substrates include tertiary amides, tertiary benzamides, aryl O-carbamates, and heteroaryl N-carbamates, which are reduced to aldehydes, benzaldehydes, aromatic alcohols, and heteroaromatics, respectively. Compared to prior methods, reagents are inexpensive and stable, reaction times are short, and reaction temperature in certain cases is conveniently room temperature. It has been estimated that using the in situ method described herein instead of synthesized or commercially obtained Schwartz Reagent provides a 50% reduction in cost

Read More
Methods and Agents for Treating Tuberculosis WO/2007/118329 A1

The present invention relates to mycobacterial infections. More specifically, it relates to therapeutic agents and methods for treating mycobacterial infections.  

Read More