Asymmetric aldol reactions are a powerful method for the construction of carbon-carbon bonds in an enantioselective fashion. Historically this reaction has been performed in a stoichiometric fashion to control the various aspects of chemo-, diastereo-, regio- and enantioselectivity, however, a more atom economical approach would unite high selectivity with the use of only a catalytic amount of a chiral promoter. This critical review documents the development of direct catalytic asymmetric aldol methodologies, including organocatalytic and metal-based strategies. New methods have improved the reactivity, selectivity and substrate scope of the direct aldol reaction and enabled the synthesis of complex molecular targets

A ring expanded bryostatin analogue was synthesized by utilizing a Ru-catalyzed tandem tetrahydropyran formation, a Pd-catalyzed tandem dihydropyran formation, and a ring-closing metathesis (RCM) as key steps. The analogue possesses potent anti-tumor activity against the NCI-ADR cancer cell line with an IC 50 of 123 nM. The bryostatins are a family of marine natural products that display a wide range of biological activities, most notably their anticancer activity in vivo. 1 This effect is attributed to their ability to modulate the functions of protein kinase C isozymes within cells. One of the members of this family, bryostatin 1, is currently is several phase I and phase II clinical trials for the treatment of several cancers. 2 The syntheses of bryostatins and their analogues have been an active research area since the structure elucidation of bryostatin 1 in 1982. 3 To date, three total and one formal syntheses have been reported 4-7 and potent bryostatin analogues 8 have been identified. In the analogue synthesis front, efforts have been centered on the simplification of the 26-membered macrolactone backbone. Herein, we report the synthesis of a ring expanded analogue 1 (Scheme 1), which retains all the functionalities in the bryostatins, and its biological activities against several cancer cell lines. Shown in Scheme 1 is our retrosynthetic analysis. Inspired by the Bring and C-ring segments, we developed a Ru-catalyzed tandem process 9 for the synthesis of 4-methylene-cis-2,6tetrahydropyran and a Pd(II)-catalyzed tandem reaction 10 for the synthesis of dihydropyrans. Since our Pd(II)-catalysis necessitates an early installation of the sensitive α,β-unsaturated methyl ester at C(13), we decided to evaluate a ring-closing metathesis (RCM) approach for the formation of the macrocycle. 11,12 The steric hindrance of the C(16)-C(17) double bond (bryostatins numbering) made this approach risky, but we were encouraged by the potential to access ring-expanded analogues. 13 Our synthesis of the northern hemisphere 2 is outlined in Scheme 2. The alcohol 9 14 was converted to the hydroxyketone 12 following a procedure 5 from Evans. Subsequent hydroxyldirected anti-reduction, 15 lactonization, 16 and protection gave lactone 14. At this stage, a β,γ-unsaturated ketone was introduced to give 5. The key Ru-catalyzed tandem coupling between enone 5 and homopropargylic alcohol 4 furnished tetrahydropyran 15 in 56% yield as a 9:1 cis:trans diastereomeric mixture, no double bond isomer was observed. Although excess 5 (2.2 equivalents) were used in the reaction, 1.2 equivalents were recovered and recycled. Subsequent bromination and deprotection gave the corresponding diol, which was subjected to a tandem lactone methanolysis-ketolization to afford 16. Compound 16 was converted to vinyl bromide 16 and then the northern hemisphere 2 in 8 steps. Our synthesis of the southern hemisphere 3 commenced with D-glactonic acid 1,4-lactone (Scheme 3). Epoxide opening of 18 17 with methyl propionate delivered methyl ynoate 19,

Leustroducsin B exhibits a large variety of biological activities and unique structural features. An efficient and highly convergent total synthesis of Leustroducsin B was achieved in 17 longest linear and 39 total steps by disconnecting the molecule into three fragments having similar levels of complexity. These pieces were connected via a highly efficient chelate-controlled addition of a vinyl zincate to an α-hydroxy ketone and a silicon-mediated cross-coupling. The stereochemistry of the central and western fragments was set catalytically in high yields and excellent de by a zinc-ProPhenol-catalyzed aldol reaction and a palladium-catalyzed asymmetric allylic alkylation.

The reaction of the bisulfite ion with aldehydes to form charged bisulfite adducts is a well-established method for the purification of aldehydes. This reaction has been modified to create a convenient liquid−liquid extraction method for the removal of aldehydes from mixtures. The use of a water-miscible solvent allows the reaction to occur during a simple 30 s shaking protocol by increasing the contact between the bisulfite ion and the aldehyde. The introduction of an immiscible solvent allows for the extraction of the uncharged organic components away from the bisulfite adduct. The developed protocol is applicable to a wide range of aldehydes, including sterically hindered neopentyl aldehydes. Sterically unhindered cyclic and linear ketones, as well as highly electrophilic ketones, are also removed using this protocol. The mild conditions tolerate a wide range of functional groups, allowing for excellent aldehyde contaminant removal rates with high levels of recovery of the desired component.

Fostriecin and related natural products present a significant challenge for synthetic chemists due to their structural complexity and chemical sensitivity. This review will chronicle the successful efforts of synthetic chemists in the construction of these biologically active molecules. Key carbon–carbon bond forming reactions will be highlighted, as well as the methods used to install the numerous stereocenters present in this class of compounds.

Highly enantioselective vicinal iodoamination of olefins is accomplished through the iodocyclization of alkenyl trichloroacetimidates catalyzed by a new chiral Schiff-base urea derivative. The resulting products are converted readily to a variety of polyfunctional amine-containing chiral building blocks.

Irradiation of biphenyl encapsulated in the cavities of a NaZSM-5 zeolite framework has been reported to result in the formation of an extremely long-lived radical cation. Here, we show that such zeolite encapsulated radical cations can act as irreversible one-electron oxidants for simple alkenes and dienes, in a solid-state analogue to solution-phase cosensitization. Compared to the well-known semiconductor photooxidizers, such as titanium dioxide, the NaZSM-5 zeolite-based solid photooxidants exhibit enhanced selectivity based on oxidation potential, molecular size and shape, and Lewis base character.

This article describes chemoselective and atom-economical methods for the stereoselective assembly of the A- and B-ring subunits of the bryostatins. A Ru-catalyzed tandem alkene-alkyne coupling/Michael addition was developed and applied to the synthesis of the bryostatin B-ring. We explored an acetylide-mediated epoxide-opening/6-exo-dig cyclization route to access the bryostatin A-ring; and the A-ring was eventually furnished via an acid-catalyzed tandem transketalization/ketalization sequence. In addition, a dinuclear zinc-catalyzed methyl vinyl ketone (MVK) aldol strategy was evaluated for the construction of the polyacetate moiety. Utilization of these methods ultimately led to the rapid assembly of a northern bryostatin fragment containing both the A- and B-ring subunits.