Rychnovsky and coworkers have described a Re(VII)-catalyzed Prins cyclization using commercially available O₃ReOSiPh₃. Usually strong Bronsted or Lewis acids effectively promote Prins cyclizations and therefore the use of a Re(VII) catalyst in a Prins cyclization is novel and noteworthy. Additionally, the chemistry is effective with both electron-rich and electron-poor aldehydes and provides access to the alcohol in the 4-position resulting from equatorial positioning of the substituent. The mechanism is currently under investigation, but a the proposed rationale involves formation of the hemiacetal upon reaction with the aldehyde electrophile followed by formation of the Re-ester intermediate, solvolysis, and cyclization to the THP as shown below.

Tadpetch, K.; Rychnovsky, S. D. Org. Lett. ASAP.

Shen and Hartwig have recently described an efficient catalyst system comprised of PdCl₂ and (R)-1-[(S_P)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine for the amination of heteroaryl and aryl halides. Since the complex itself is air- and moisture-stable, it does not need to be prepared in situ, which consequently results in lower catalyst loadings (0.001-0.05 mol %). The amination was observed to be fastest with aryl bromides, followed by aryl chlorides, while aryl iodides required higher catalyst loadings (5-10 times higher). The amination reactions using [(CyPF-tBu)PdCl₂] are very generally and exhibit excellent functional group compatibility (cyano, ketone free carboxylates, amido, carboalkoxy, aromatic, and aliphatic hydroxyl and amino functional groups are all tolerated). Reactions containing any protic functional groups are conducted in the presence of 2 equiv of LiHMDS in place of NaOtBu.

Shen, Q.; Hartwig, J. F. Org. Lett. 2008, 10, 4109.

If you didn’t catch the September 15th Issue of Chemical & Engineering News yet, grab a copy and check out the article “Elements Achieve Internet Stardom”. C&EN reports that chemistry Professor Martyn Poliakoff (University of Nottingham, UK) has made the Period Table of Elements a YouTube star in its own right.

The documentary-styled videos debuted July 17th and have generated quite a buzz among Nobel Laureates, chemistry professors, students and their parents. With the appearance of a stereotypical mad scientist, this non-scientist found the videos entertaining and educational, and Professor Poliakoff simply oozing with British charm and humor. No more mysterious wall charts for me. No searching Wiki’s endlessly learning the elements. Just straight up information and fascinating demonstrations (some dangerous for even trained chemists – do not attempt these at home warnings included).

The videos can be found at www.youtube.com/periodicvideos and for those of you at schools or institutions who are blocked from YouTube visit http://www.periodicvideos.com/. ENJOY! I know I did.

The 3rd Negishi-Brown Lectures - CAOSS Short Course will take place October 13th & 14, 2008 at Purdue University in West Lafayette, Indiana USA. Come learn about the latest advances in asymmetric synthesis from such reknowned educators as:

M. P. Doyle (U. of Maryland)
S. Hanessian (U. of Montreal)
D. R. Williams (Indiana U.)
E. Negishi (Purdue U.)
P. Kündig (U. of Geneva)
M. Krische (U. of Texas, Austin)
T. V. RajanBabu (Ohio St. U.)
P. Walsh (U. of Pennsylvania)

Registration Fees

FREE Student or Postdoctoral Associate (inclds 2 lunches, refreshments & mixer on 10/13)
Outside Academician (beyond Post. Doc.) $50 (inclds 2 lunches, refreshments, & mixer on 10/13)
Industrial Chemist $I50 (inclds 2 lunches, refreshments &mixer on 10/13)

 Visit sigma-aldrich.com  for more information and registration form. Deadline for registration is September 26, 2008.

Basle and Li have described a regioselective sp³ C-H bond arylation of tetrahydroisoquinolines using an inexpensive copper catalyst (CuBr), and T-HYDRO^® (or O₂) in dimethoxyethane in the absence of a directing group. Tetrahydroisoquinolines are important moieties, which display pharmacological and physiological effects. The authors also began a preliminary investigation towards the development of an enantioselective version, and found the use of (R,R)-2,6-Bis(4,5-dihydro-4-phenyl-2-oxazolyl)pyridine (PhPyBox) ligand provided the product in combination with CuOTf as the copper source in 44% ee. Two possible mechanisms for the Cu-catalyzed C-H arylation were proposed, both of which proceed via a common iminium ion-Cu alkoxide intermediate (regioselectively likely a result of stabilized benzylic position). The more likely possibility involves Cu-catalyzed C-C bond formation between the iminium ion-Cu-alkoxide species and the aryl boronic acid.

 Basle, O.; Li, C-J. Org. Lett. 2008, 10, 3661.

Biaryls are present in a plethora of natural products, pharmaceuticals, polymers, sensors and ligands and their synthesis often involves a cross coupling reaction, such as a Stille, Suzuki, Negishi, or Hiyama coupling. Akai and coworkers have recently disclosed a three-component approach, involving a Diels-Alder reaction followed by a Hiyama coupling utilizing a silylated benzyne, a furan derivative, and an aryl iodide. The optimal silylated benzyne derivative contains a TBDMS group, which provided good regioselectivity in the Diels-Alder reaction. After regioselective cleavage (pTsOH·H₂O or [Cp*RuCl(cod)] ) of the epoxy ring to afford the alcohol, a Hiyama coupling (Ar-I, [(allyl)PdCl]₂, AsPh₃, Cs₂CO₃, DME, 60 °C) provides (after silyl group activation and migration to the neighboring alcohol) the cross-coupled biaryl. 

Akai, S.; Ikawa, T.; Takayanagi, S-i.; Morikawa, Y.; Mohri, S.; Tsubakiyama, M.; Egi, M.; Wada, Y.; Kita, Y. Angew. Chem. Int. Ed. 2008, 47, ASAP.

Belot and coworkers have recently demonstrated an enantioselective 1,4-addition of aldehydes to nitrodienes using a diphenylprolinol silyl ether organocatalyst. The reaction is feasible with a variety of substituted aldehydes and nitrodienes providing the 1,4-adduct with good levels of diastereo- and enantiocontrol using low loadings of  (S)-(?)-alpha,alpha-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether. The synthetic utility of the reaction was also demonstrated via treatment of the 1,4 adduct with NaBH₄ in MeOH to afford the alcohol, followed by treatment with PhSeCl to provide the tetrahydropyran. Additionally, hexen-5-al was converted to a cyclohexene derivative after the conjugate addition and treatment with the Grubbs II catalyst.

Belot, S.; Massaro, A.; Tenti, A.; Mordini, A.; Alexakis, A. Org. Lett. ASAP.

Lu and Falck have recently reported an iridium-catalyzed C-H functionalization/silylation of N-, S-, and O- heteroarenes, which allows access to silyl-substituted arenes that are prevalent and useful to both synthetic and materials scientists. Using [{Ir(OMe)(cod)}₂] as the catalyst, in the presence of Et₃SiH, 4,4-di-tert-butyl-2,2-bipyridine, and norbornene, the silylation of the heteroarene occurs readily at 80 °C, placing the silyl group in the 2-position (except in one case). The use of C-H bond functionalization for the preparation of aryl silanes is complementary and in some ways superior to other know methods for their preparation. While other C-H bond functionalization methods are often limited with respect to regioselectivity, harsh reaction conditions, substrate structural requirements, and unfeasible ratios of reagents relative to each other, Lu and Falck?s method is regioselective, mild, and tolerates a broad range of functionality. The mechanism has not yet been investigated, but the authors propose coordination of the catalyst to the N, O, or S, followed by insertion into the adjacent C-H bond.

Lu, B.; Falck, J. R. Angew. Chem. Int. Ed. ASAP.

Written by William Sommer, PhD

The development of gold catalysis has been an endeavor for the past 10 years.¹ One of the leaders in this field, professor Toste and coworkers, developed a new way to synthesize azepines via a gold catalyzed intermolecular [4+3]-annulation.² In this study, the authors demonstrated the efficiency of the transformation, catalyzed by PicAuCl₂, with a variety of substrates. It was noted that the substrates containing electron-rich N-aryl groups gave the highest yields. In a typical procedure, 2 to 10 mol% of the gold catalyst is needed in methylene chloride at room temperature. Good to excellent yields are obtained with good diastereomic ratios.