A new class of bidirectionally quantitative photoswitches based on the hemithioindigo (HTI) scaffold is reported. Incorporation of a pyrrole hydrogen-bond donor leads to a bathochromic shift allowing for quantitative bidirectional isomerization. Additionally, extending conjugation from the electron-rich pyrrole results in quantitative visible-light photoswitches, as well as photoswitches that isomerize with red and near-infrared light. The presence of the hydrogen bond leading to the observed redshift is supported by computational and spectroscopic evidence.

A 13-step total synthesis of the fungal meroterpenoid berkeleyone A is reported. The molecular skeleton is formed using the first examples of two critical construction reactions: (1) an epoxide-initiated, β-ketoester-terminated polycyclization, and (2) an isomerization–cyclization cascade to generate the remaining bicyclo[3.3.1]nonane framework. The resulting 6-step synthesis of the carbocyclic core of the berkeleyone natural products has been used to access protoaustinoid A and berkeleyone A, and will aid future biosynthetic investigations into the origin of related natural products.

AbstractThe telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.

AbstractA highly practical and step-economic α,β-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2⋅2 LiCl as a base in the presence of excess ZnCl2, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches.

AbstractA highly practical and step-economic α,β-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2⋅2 LiCl as a base in the presence of excess ZnCl2, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches.

AbstractMeroterpenes derived from dimethylorsellinic acid (DMOA) and farnesyl pyrophosphate have attracted much biosynthetic attention, yet only recently have synthetic solutions to any family members appeared. A key point of divergence in DMOA-derived meroterpene biosynthesis is the protoaustinoid A carbocation, which can be diverted to either the berkeleyone, andrastin, or terretonin structural classes by cyclase-controlled rearrangement pathways. Shown herein is that the protoaustinoid bicyclo[3.3.1]nonane nucleus can be reverted to either andrastin or terretonin ring systems under abiotic reaction conditions. The first total syntheses of members of these natural product families are reported as their racemates.

AbstractThe telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.

Several Gold's reagents were synthesized from cyanuric chloride and N,N-dialkylformamides. These synthetic equivalents of N,N-dimethylformamide dimethyl acetal were used in an optimized and scalable procedure for the regioselective synthesis of a variety of enaminones from ketone starting materials, whose utility was demonstrated by the stereoselective synthesis of Rawal-type dienes.Download high-res image (144KB)Download full-size image

We report the first total synthesis of the limonoid andirolide N using a 12-step sequence from commercially available materials. The final step of this route demonstrates the chemical feasibility of our biosynthetic proposal that andirolide N arises from 8α-hydroxycarapin. The strategic use of a degraded limonoid as a platform for the synthesis of more structurally complex congeners may be a general approach to obtain limonoids with diverse functional properties.

A practical and direct method for the α,β-dehydrogenation of amides is reported using allyl-palladium catalysis. Critical to the success of this process was the synthesis and application of a novel lithium N-cyclohexyl anilide (LiCyan). The reaction conditions tolerate a wide variety of substrates, including those with acidic heteroatom nucleophiles.

An improved protocol for the formal elimination of propene from organic substrates is reported. This process entails the ozonolytic conversion of an alkene to a methoxy hydroperoxide which undergoes fragmentation mediated by copper and iron. The use of soluble Cu(BF4)2 and Fe(BF4)2 results in reproducible results up to a 100 gram scale.

A highly practical and general palladium-catalyzed methodology for the α,β-dehydrogenation of esters and nitriles is reported. Generation of a zinc enolate or (cyanoalkyl)zinc species followed by the addition of an allyl oxidant and a palladium catalyst results in synthetically useful yields of α,β-unsaturated esters, lactones, and nitriles. Preliminary mechanistic investigations are consistent with reversible β-hydride elimination and turnover-limiting, propene-forming reductive elimination.

An improved protocol for the formal elimination of propene from organic substrates is reported. This process entails the ozonolytic conversion of an alkene to a methoxy hydroperoxide which undergoes fragmentation mediated by copper and iron. The use of soluble Cu(BF4)2 and Fe(BF4)2 results in reproducible results up to a 100 gram scale.