Alkenes and arenes represent two classes of feedstock compounds whose union has fundamental importance to synthetic organic chemistry. We report a new approach to alkene arylation using diaryliodonium salts and Cu catalysis. Using a range of simple alkenes, we have shown that the product outcomes differ significantly from those commonly obtained by the Heck reaction. We have used these insights to develop a number of new tandem and cascade reactions that transform readily available alkenes into complex arylated products that may have broad applications in chemical synthesis.

An efficient method for the asymmetric gold(I)-catalyzed preparation of medium sized rings has been developed. The method provides 7-to 9-membered rings in excellent yield. High enantioselectivities can be achieved for 7-and 8-membered ring products employing chiral gold(I) complexes. The results provide insight into the mechanism, showing the fluxional nature of gold(I)-stabilized vinyl carbenoid intermediates.The construction of medium sized rings is an important and challenging goal in organic synthesis. 1 Transition metal catalyzed cycloisomerization and cycloaddition reactions are powerful methods to access these ring systems. 2 However, only a few of these methods are applicable to the enantioselective synthesis of medium-sized rings. 3 Although cyclization with rhodium carbenes generated from diazo-precursors has provided some limited success, dimerization can be a significant problem. 4 On the other hand, dimerization of the propargyl ester derived gold(I)-carbenoid is absent in the gold(I)-catalyzed asymmetric olefin cyclopropanation reaction (eq 1). 5a Moreover, the reactions of propargyl esters represent a rare class of gold-catalyzed carbon-carbon bond forming transformations that work efficiently in an intermolecular sense. 5-7 Given this unique reactivity, we hypothesized that the goldcatalyzed olefin cyclopropanation reaction might provide an opportunity for the enantioselective preparation of medium-sized ring compounds, 5,6a despite the fact that enantioselective gold(I)-catalyzed enyne cycloisomerization reactions remain rare. 8(1)We were pleased to find that triphenylphosphinegold(I)-catalyzed the cycloisomerization of propargyl ester 3 to cycloheptene 4 in quantitative yield (eq 2). 9,10 A similar result was fdtoste@berkeley.edu. obtained for the formation of 8-membered ring 6 from propargyl ester 5. The gold-catalyzed intramolecular cyclopropanation reaction also allowed for the synthesis of a 9-membered ring, albeit in diminished yields. 11 Surprisingly, reaction of propargyl ester 1 provided 6-membered ring product 2 in only 10% yield. 12 Moreover, reaction of 3 or 5 in the presence of styrene only resulted in the intramolecular 7-or 8-membered ring products (4 and 6 respectively); no intermolecular cyclopropanation was observed. NIH Public Access(2)On the basis of these results we turned our attention towards the development of a catalytic enantioselective intramolecular cyclopropanation. To this end, we first examined the catalyst system developed for the intermolecular enantioselective cyclopropanation reaction (eq 1); however, we were disappointed to find that under these conditions cyclooctene 10 was formed with very low enantiomeric excess (Table 1, entry 1). Further experiments found that the BINAP family of ligands was optimal with xylyl-BINAP giving the highest enantioselectivity (entries 2-4). In contrast to the intermolecular reaction in which pivaloate esters were required to achieve high enantioselectivity, acetate ester 9 afforded the cyclopropane with noticeably bett...

Bacopa monnieri is an Ayurvedic plant with rising interest in the pharmacological effects of its extract and constituents, including flavonoids, saponins, and triterpenes such as cucurbitacins, betulinic acid, and bacosine. The latter two compounds are isomeric 3-hydroxy lupenoic acids, which vary only in the arrangement of the carboxylic acid group and the methyl group at C-27 and C-28 and the orientation of the hydroxy group at C-3. In this study, we have reinvestigated the contents of betulinic acid and bacosine, respectively, in extracts from various commercially available B. monnieri powders and food supplements. To our surprise, HPLC-ion trap time-of-flight analyses identified only betulinic acid, but not bacosine, in all extracts under study, which was verified by GC-MS, HPLC-ELSD, 1D NMR (1H,13C), and 2D NMR (1H,1H COSY, 1H,13C HMBC, 1H,13C HSQC, 1H,1H NOESY) experiments. Moreover, it turned out that commercially available reference samples of bacosine were structurally identical with betulinic acid.

A synthetic approach towards (5R)‐5‐methyl‐6‐oxa‐desacetamido colchicine as a conformationally defined non‐natural colchicine analog with a modified B‐ring was undertaken. The synthetic strategy was based on a Rh‐catalyzed cascade reaction involving a [5+2] cycloaddition of a carbonyl ylide intermediate as a key step, in which both seven‐membered rings of the polycyclic framework are formed in a single operation. Starting from 2‐iodo‐3,4,5‐trimethoxy‐acetophenone, an upper side‐chain was constructed through enantioselective CBS reduction (up to 75 % ee) and propargylation, while a lower succinoyl side‐chain was attached either throughiodine–magnesium–copper exchange and subsequent reaction with methyl 4‐chloro‐4‐oxobutanoate, or by Pd‐catalyzed Stille cross‐coupling with 2‐tributylstannyl‐5‐methoxyfuran followed by hydrolytic furan‐opening. Treatment of an α‐diazoketone intermediate with Rh2(OAc)4 (3 mol‐%)initiated the diastereoselective key cyclization cascade (≥97:3 dr). Treatment of the cycloadduct 3 with Et2AlCl afforded an interesting 11,12‐dihydrocolchicine analog 24, which, however, could not be oxidized to the corresponding tropolone. Structural assignments were confirmed by X‐ray crystallography. While compounds 3 and 24 did not exhibit noteworthy cytotoxic activity by themselves, they were found to strongly enhance the cytostatic (apoptosis‐inducing) activity of doxorubicin against resistant Nalm‐6 cells (i.e., in a synergy effect).