Weidong Rao

Gold-catalyzed cycloisomerization reactions of 2-tosylaminophenylprop-1-yn-3-ols as a versatile approach for indole synthesis.

] decomposes (2) andautocatalytically grows to pure Fe nanocrystals (3) at predefined positions until theprecursor supply is stopped. In their Communication on page 4669 ff., H. Marbachet al. describe how the two-step process might be the starting point of a novel way togenerate nanostructures (see the 3D representation of the SEM data in thebackground).Nanoporous Metal FoamsThe controlled combustion of metal bistetrazolamine complexes offers a route to awide variety of metal foams that have a nanoporous structure. The development ofthis area is documented by B. C. Tappan et al. in their Review on page 4544 ff.C O Bond ActivationD. J. Shi et al. report in their Communication on page 4566 ff. on the first successfulcoupling reaction involving the direct application of naphtholates as electrophiles.InfochemistryIn their Communication on page 4571 ff., G. Whitesides et al. describe “infofuses”,which are systems for non-electronic communication consisting of a fast-burningnitrocellulose fuse and a slow-burning cotton fuse.

Gold-Catalyzed Tandem 1,3-Migration/[2 + 2] Cycloaddition of 1,7-Enyne Benzoates to Azabicyclo[4.2.0]oct-5-enes

A synthetic method that relies on gold(I)-catalyzed tandem 1,3-migration/[2 + 2] cycloaddition of 1,7-enyne benzoates to prepare azabicyclo[4.2.0]oct-5-enes is described.

Gold-Catalyzed Cycloisomerization of 1,7-Diyne Benzoates to Indeno(1,2-c)azepines and Azabicyclo(4.2.0)octa-1(8),5-dines

A synthetic method that relies on Au(I)-catalyzed cycloisomerization reactions of 1,7-diyne benzoates to prepare indeno[1,2-c]azepines and azabicyclo[4.2.0]octa-1(8),5-dines is described.

Gold‐Catalyzed Tandem Intramolecular Heterocyclization/Petasis–Ferrier Rearrangement of 2‐(Prop‐2‐ynyloxy)benzaldehydes as an Expedient Route to Benzo[b]oxepin‐3(2 H)‐ones

Partially or fully hydrogenated benzo[b]oxepines are common ring motifs found in many pharmaceutically interesting and potentially bioactive natural compounds. Representative examples range from the structurally simple and bioactive heliannuol A, pterulone, and radulanin A to the architecturally challenging compounds edulisone A and ovafolinin B. For this reason, the establishment of new synthetic methods to construct this biologically important class of compounds has received an immense amount of attention. The synthetic strategies toward functionalized benzo[b]oxepines can be divided into two groups: manipulation of a pre-existing oxygen-containing cyclic core or assembly from acyclic precursors. Despite the advances made through both these approaches, the development of new synthetic methods to prepare this class of oxygen heterocycles from readily available substrates and catalysts with selective control of substitution patterns under mild and operationally simplistic conditions remains desirable. The emergence of gold complexes as powerful and versatile Lewis acid catalysts that can mediate a plethora of C X (X=C, N, O, S) bond formations has been well documented in recent years. Among this myriad of works, one notable innovation has been the formation of carbocycles and heterocycles from cyclization of a carbonyl compound tethered to an alkyne in the presence of a gold catalyst. For example, Yamamoto and Jin recently reported an efficient synthetic route to fused triand tetracyclic enones based on the AuCl3/AgSbF6-catalyzed tandem heteroenyne metathesis/Nazarov cyclization of 1,3-enynyl ketones. On the basis of this and other previous studies on carbonyl metathesis, we reasoned that a strategy that made use of Opropargylated salicylaldehydes in the presence of a Lewis acid gold catalyst would hold promise as a new method for benzo[b]oxepin-3 ACHTUNGTRENNUNG(2H)-one synthesis. As part of an ongoing program exploring the scope of gold catalysis in heterocyclic synthesis, our discovery that Au complex 3 can effect tandem intramolecular heterocyclization/Petasis–Ferrier rearrangement of 2-(prop-2-ynyloxy)benzaldehydes is reported herein (Scheme 1). This process provides a convenient synthetic route to benzo[b]oxepin-3ACHTUNGTRENNUNG(2H)-ones in 21– 99% yield for a wide variety of substrates under mild and operationally simplistic conditions that did not require the exclusion of air or moisture. A study that delineates the influence on reactivity of a substituent at the ortho position to the ethereal moiety on the salicylaldehyde is also presented. To the best of our knowledge, synthetic methods involving metal-mediated cyclizations of propargylic aldehydes of type 1 have thus far been reported to typically give the benzopyran product. We began by examining the cyclization of 1a by a variety of Lewis and Bronsted acids to establish the optimal reaction conditions (Table 1 and Table S1 in the Supporting In[a] E. M. L. Sze, Dr. W. Rao, M. J. Koh, Prof. Dr. P. W. H. Chan Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University Singapore 637371 (Singapore) Fax: (+65)6791-1961 E-mail : waihong@ntu.edu.sg Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201003096. Scheme 1. Gold(I)-catalyzed synthesis of benzo[b]oxepin-3 ACHTUNGTRENNUNG(2H)-ones from 2-(prop-2-ynyloxy)benzaldehydes. R=H, alkyl, aryl, halide, or NO2; R , R=H or alkyl.

Gold-and Silver-Catalyzed Tandem Amination/Ring Expansion of Cyclopropyl Methanols with Sulfonamides as an Expedient Route to Pyrrolidines

An efficient synthetic route to pyrrolidines that relies on AuCl/AgOTf-catalyzed tandem amination/ring expansion of substituted cyclopropyl methanols with sulfonamides is reported herein. The reactions proceed rapidly at 100 degrees C with catalyst loadings as low as 2 mol % and produce the pyrrolidine products in yields of 30-95 %. The method was shown to be applicable to a broad range of cyclopropyl methanols, including unactivated ones, and sulfonamide substrates containing electron-withdrawing, electron-donating, and sterically-demanding substituents. The mechanism is suggested to involve activation of the alcohol substrate by the AuCl/AgOTf catalyst, followed by ionization of the starting material, which causes ring opening of the cyclopropane moiety and trapping by the sulfonamide nucleophile. The resultant aminated acyclic intermediate undergoes subsequent intramolecular hydroamination to give the pyrrolidine.

Ytterbium(III) triflate-catalyzed amination of 1-cyclopropylprop-2-yn-1-ols as an expedient route to conjugated enynes.

Ytterbium(III) triflate-catalyzed ring opening of substituted 1-cyclopropyl-2-propyn-1-ols with sulfonamides as an efficient synthetic route to conjugated enynes is described herein. The reaction was operationally straightforward and accomplished in moderate to good yields and regioselective manner in all except one case under mild conditions.

Rapid Access to Halohydrofurans via Brønsted Acid-Catalyzed Hydroxylation/Halocyclization of Cyclopropyl Methanols with Water and Electrophilic Halides

A one-pot, two-step method to prepare 3-halohydrofurans efficiently by TfOH-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with H(2)O and N-halosuccinimide (NXS, X=1, Br, Cl) or Selectfluor is described. The reactions proceed rapidly under mild and operationally straightforward conditions with a catalyst loading as low as 1 mol % and afford the 3-halohydrofuran products in moderate to excellent yields and, in most cases, with preferential cis diastereoselectivity. The method was shown to be applicable to cyclopropyl methanols containing electron-withdrawing, electron-donating, and sterically demanding functional groups and electrophilic halide sources. The mechanism is suggested to involve protonation of the alcohol substrate by the Brønsted acid catalyst and ionization of the starting material. This results in ring-opening of the cyclopropane moiety and in situ formation of a homoallylic alcohol intermediate, which undergoes subsequent intramolecular halocyclization on treating with the electrophilic halide source to give the halohydrofuran. The observed cis product selectivity is thought to be determined by the reaction proceeding through an in situ generated unsaturated alcohol intermediate that contains a (Z)-alkene moiety under the kinetically controlled conditions.

Cyclopropyl Carbinol Rearrangement for Benzo-Fused Nitrogen Ring Synthesis

A synthetic method that relies on gold-catalysed cyclopropyl carbinol rearrangement of 2-tosylaminophenyl cyclopropylmethanols to prepare 2,3-dihydro-1H-benzo[b]azepines and 2-vinylindolines efficiently is reported. The reactions were shown to be chemoselective, with secondary and tertiary alcohol substrates exclusively providing benzo-fused five- and seven-membered ring products, respectively. The ring-forming process was also found to proceed in moderate to excellent yields under mild conditions only in the presence of the gold and silver catalyst combination. The mechanism is thought to involve activation of the alcohol by the (p-CF(3)C(6)H(4))(3)PAuCl/AgOTf (Tf = triflate) catalyst, resulting in ionization of the starting material. The tertiary carbocationic intermediate generated in situ in this manner then triggers ring-opening of the cyclopropane moiety and trapping by the tethered aniline group to give the 2,3-dihydro-1H-benzo[b]azepine. Cyclopropane ring fragmentation of the secondary carbocationic analogue, on the other hand, results in diene formation followed by subsequent intramolecular hydroamination to afford the 2-vinylindoline.

Gold-catalyzed [2+2+1] cycloaddition of 1,6-diyne carbonates and esters with aldehydes to 4-(cyclohexa-1,3-dienyl)-1,3-dioxolanes

A synthetic method to stereoselectively prepare 4-(cyclohexa-1,3-dienyl)-1,3-dioxolanes in good to excellent yields by gold(I)-catalyzed [2+2+1] cycloaddition of 1,6-diyne carbonates and esters with aldehydes is described. The cascade process involves 1,2-acyloxy migration followed by cyclopropenation and cycloreversion. This leads to an unprecedented [2+2+1] cycloaddition of the resulting alkenylgold carbenoid species, examples of which are extremely rare, with two aldehyde molecules at catalyst loadings as low as 1 mol %. The usefulness of this cycloisomerization chemistry was further demonstrated by the transformation of one example to the corresponding phenol.

Gold-Catalyzed Domino Aminocyclization/1,3-Sulfonyl Migration of N-Substituted N-Sulfonyl-aminobut-3-yn-2-ols to 1-Substituted 3-Sulfonyl-1H-pyrroles

A method to prepare 1-substituted 3-sulfonyl-1H-pyrroles efficiently that relies on the gold(I)-catalyzed cycloisomerization of N-substituted N-sulfonyl-aminobut-3-yn-2-ols is described. The method was shown to be applicable to a broad range of 1,7-enyne alcohols containing electron-withdrawing, electron-donating, and sterically demanding substrate combinations. The mechanism is suggested to involve activation of the propargylic alcohol by the Au(I) catalyst, which causes the intramolecular nucleophilic addition of the sulfonamide unit to the alkyne moiety. The resulting nitrogen-containing heterocyclic intermediate undergoes dehydration and deaurative 1,3-sulfonyl migration, a process that remains rare in gold catalysis, to give the aromatic nitrogen-containing product.