Search

The synthesis of structurally complex and highly strained natural products provides unique challenges and unexpected opportunities for the development of new reactions and strategies. Herein, the synthesis of (+)-[5]-ladderanoic acid is reported. En route to the target, unusual and unexpected strain release driven transformations were uncovered. This occurrence required a drastic revision of the synthetic design that ultimately led to the development of a novel stepwise cyclobutane assembly by an allylboration/Zweifel olefination sequence.

Rigid bicycles are becoming more popular in the pharmaceutical industry because they allow for expansion to new and unique chemical spaces. This work describes a new strategy to construct 2‐azanorbornanes, which can act as rigid piperidine/pyrrolidine scaffolds with well‐defined exit vectors. To achieve the synthesis of 2‐azanorbornanes, new strain‐release reagent, azahousane, is introduced along with its photosensitized strain‐release formal cycloaddition with alkenes. Furthermore, new reactivity between a housane and an imine is disclosed. Both strategies lead to various substituted 2‐azanorbornanes with good selectivities. [ABSTRACT FROM AUTHOR]

The synthesis of polycyclic compounds is of high interest due to the prevalence of these motifs in drugs and natural products. Herein, we report on the stereoselective construction of 3D bicyclic scaffolds and azetidine derivatives by modulation of N‐sulfonylimines to achieve either [4+2]‐ or [2+2]‐cycloaddition reactions. The utility of the method was established by further modulation of the product. Mechanistic studies are also included, which support reaction via Dexter energy transfer. [ABSTRACT FROM AUTHOR]

The ladderane family of natural products are well known for their linearly concatenated cyclobutane skeletal structure. Owing to their unique carbocyclic framework, several chemical syntheses have been reported since their discovery in 2002. The focus of this review is to showcase the novel tactics that have been used to generate the ladderane core and the challenges that are associated with the synthesis of these unusual and complex natural products. [ABSTRACT FROM AUTHOR]

A method for the stereoselective [4+2]‐cycloaddition of alkenylboranes and dienes is presented. This transformation was accomplished through the introduction of a new strategy that involves the use of chiral N‐protonated alkenyl oxazaborolidines as dieneophiles. The reaction leads to the formation of products that can be readily derivatized to more complex structural motifs through stereospecific transformations of the C−B bond such as oxidation and homologation. Detailed computation evaluation of the reaction has uncovered a surprising role of the counterion on stereoselectivity. [ABSTRACT FROM AUTHOR]

Abstract: The first synthesis of hebelophyllene E is presented, along with assignment of its previously unknown relative configuration through synthesis of epi‐ent‐hebelophyllene E. Development of a catalytic enantioselective [2+2] cycloaddition of alkenes and allenoates provides access to the required chiral geminal dimethylcyclobutanes. Key to its success is the identification of a novel oxazaborolidine catalyst which promotes the cycloaddition in high enantioselectivities with good functional‐group tolerance (9 examples, up to 97:3 e.r.). Thus, a late‐stage cycloaddition using a fully functionalized alkene, followed by a diastereoselective reduction allows a concise entry to this class of natural products. [ABSTRACT FROM AUTHOR]

An unexpected [4+2] cycloaddition of aryl allenes and simple acrylate derivatives is reported. This process functions well with a variety of allenes and acrylates to generate bi- and tricyclic dihydronaphthalene derivatives through a nonconventional bond disconnection. [ABSTRACT FROM AUTHOR]

Cyclobutanes and cyclobutenes are important structural motifs found in numerous biologically significant molecules, and they are useful intermediates for chemical synthesis. Consequently, [2+2] cycloadditions to access cyclobutanes and cyclobutenes have been established to be particularly useful transformations. Within the last 10 years, an increase in the frequency of publications for catalytic enantioselective [2+2] cycloadditions has occurred. These reactions provide access to a wide array of enantiomerically enriched chemical diversity that was not previously attainable. Described in this review are the advances made in catalytic enantioselective [2+2] cycloadditions to access cyclobutanes and cyclobutenes. [ABSTRACT FROM AUTHOR]

The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene-alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp3)H oxidation. The synthesis requires only eight steps from norbornadiene. [ABSTRACT FROM AUTHOR]

A strategy for the photosensitized [2+2]‐cycloaddition between styrenyl dihaloboranes and unactivated allylamines to access cyclobutylboronates with control of stereochemistry and regiochemistry is presented. The success of the reaction relies on the temporary coordination between in situ generated dihaloboranes and amines under mild reaction conditions. In addition, cyclobutanes with varying substitution patterns have been prepared using N‐heterocycles as directing group. Manipulation of the C−B bond allows for the synthesis of a diverse class of cyclobutanes from simple precursors. Moreover, these reactions lead to the synthesis of complex amines and heteroaromatic compounds, which have significant utility in medicinal chemistry. Finally, a dearomative [4+2]‐cycloaddition of naphthalenes using a boron‐enabled temporary tethering strategy has also been uncovered to synthesize complex 3‐dimensional borylated building blocks. [ABSTRACT FROM AUTHOR]

The application of thioallenoates to catalytic enantioselective [2+2]-cycloadditions with unactivated alkenes is reported. In many cases, the thioallenoates examined exhibit superior reactivity and selectivity compared to the allenic esters generally used in these cycloadditions. Image 1 [ABSTRACT FROM AUTHOR]

Cyclobutanes are important motifs that have found utility in many contexts. Prior work has demonstrated an enantioselective isomerization/stereoselective [2 + 2] as a means to access bicyclo [4.2.0]octanes. Herein, the utility of this method is demonstrated towards the synthesis of benzocyclobutenes and a key intermediate towards the endiandric acids. To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. [Display omitted] [ABSTRACT FROM AUTHOR]