Philip Wai Hong Chan

Transition‐metal‐catalyzed aminations and aziridinations of CH and CC bonds with iminoiodinanes

Catalytic insertion or addition of a metal-imido/nitrene species, generated from reaction of a transition-metal catalyst with iminoiodanes, to C-H and C=C bonds offers a convenient and atom economical method for the synthesis of nitrogen-containing compounds. Following this groundbreaking discovery during the second half of the last century, the field has received an immense amount of attention with a myriad of impressive metal-mediated methods for the synthesis of amines and aziridines having been developed. This review will cover the significant progress made in improving the efficiency, versatility and stereocontrol of this important reaction. This will include the various iminoiodanes, their in situ formation, and metal catalysts that could be employed and new ligands, both chiral and non-chiral, which have been designed, as well as the application of this functional group transformation to natural product synthesis and the preparation of bioactive compounds of current therapeutic interest.

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 intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols. A concise synthesis of (+/-)-angustureine.

An efficient synthetic route to 1,2-dihydroquinolines that relies on AuCl(3)/AgSbF(6)-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols is described herein. Uniquely, the reactions were found to only proceed rapidly at room temperature in the presence of the gold and silver catalyst combination and produce the 1,2-dihydroquinoline products in yields of 40-91%. The method was shown to be applicable to a broad range of 2-tosylaminophenylprop-1-en-3-ols containing electron-withdrawing, electron-donating, and sterically demanding substrate combinations. The mechanism is suggested to involve activation of the alcohol substrate by the AuCl(3)/AgSbF(6) catalyst. This is followed by ionization of the starting material, which causes intramolecular nucleophilic addition of the sulfonamide unit to the allylic cation moiety and construction of the 1,2-dihydroquinoline. The utility of this N-heterocyclic ring forming strategy as a synthetic tool that makes use of alcohols as pro-electrophiles was exemplified by its application to the synthesis of the bioactive tetrahydroquinoline alkaloid (+/-)-angustureine.

Ytterbium(III) Triflate Catalyzed Tandem Friedel−Crafts Alkylation/Hydroarylation of Propargylic Alcohols with Phenols as an Expedient Route to Indenols

A method to prepare indenols efficiently by ytterbium(III) triflate catalyzed tandem Friedel-Crafts alkylation/hydroarylation of propargylic alcohols with phenols is described. The reaction was accomplished in moderate to excellent yields and regioselectivity under mild conditions and offers a straightforward and convenient one step synthetic route to bioactive indenols and its derivatives.

Chiral rhodium(II,II) dimers catalyzed enantioselective intramolecular aziridination of sulfonamides and carbamates

The asymmetric intramolecular aziridination of unsaturated sulfonamides and carbamates catalyzed by chiral dirhodium(II,II) complexes were achieved in good yields (up to 95%) and enantioselectivity (up to 76% e.e.).

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 Cycloisomerizations of 1-(2-(Tosylamino)phenyl)prop-2-yn-1-ols to 1H-Indole-2-carbaldehydes and (E)-2-(Iodomethylene)indolin-3-ols

A method to prepare 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols by gold(I)-catalyzed cycloisomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols with N-iodosuccinimide (NIS) is reported. The reactions were shown to be operationally simplistic and proceed efficiently for a wide variety of substrates, affording the corresponding products in good to excellent yields (70-99%). The mechanism is suggested to involve activation of the alkyne moiety of the substrate by the gold(I) catalyst. This triggers intramolecular addition of the tethered aniline moiety to give a vinyl gold intermediate, which undergoes iododeauration with NIS to give the (E)-2-(iodomethylene)indolin-3-ol adduct. Subsequent 1,3-allylic alcohol isomerization (1,3-AAI) followed by formylation of this vinyl iodide intermediate then gives the 1H-indole-2-carbaldehyde.

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.