Alistair Boyer

Rhodium(II)-Catalyzed Stereocontrolled Synthesis of Dihydrofuran-3-imines from 1-Tosyl-1,2,3-triazoles

Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to give substituted dihydrofuran-3-imines in high yield and diastereoselectivity.

The Azadirachtin Story

Azadirachtin has been the subject of intensive research within the scientific community ever since its isolation from the neem tree in 1968. There are now over 1000 publications relating to this natural product which cover all aspects of structural, biological and synthetic studies. Herein, we describe the worldwide synthesis efforts towards this fascinating molecule.

Practical Asymmetric Synthesis of Bioactive Aminotetralins from a Racemic Precursor Using a Regiodivergent Resolution

Catalyst-controlled asymmetric ring opening of a racemic oxabicyclic alkene leads to two readily separable regioisomeric products both in excellent ee. A cationic Rh catalyst, with added NH(4)BF(4) to modulate reactivity, was required to obtain synthetically useful yields. The utility of each substituted aminotetralin product has been demonstrated by their conversion to different biologically relevant molecules in a highly efficient and practical manner.

Rhodium(II)-Catalyzed Stereocontrolled Synthesis of 2-Tetrasubstituted Saturated Heterocycles from 1-Sulfonyl-1,2,3-triazoles

Rhodium(II) acetate catalyzes the denitrogenative transformation of 4-substituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ethers and thioethers to onium ylides that undergo [2,3]-sigmatropic rearrangement to give 2-tetrasubstituted heterocycles with high yield and diastereoselectivity.

Organocatalytic Synthesis of Highly Substituted Furfuryl Alcohols and Amines

A simple organocatalytic synthesis of substituted furans has been developed. The novel features of the procedure include the use of a simple thioether as the organocatalyst, the formation of a furan under neutral conditions rather than the anionic or acidic conditions employed in conventional syntheses, and the intermediacy of a versatile sulfonium ylide that has the potential to be intercepted directly by a variety of electrophiles rather than being protonated to give a sulfonium ion. The reaction proceeds with a wide range of substrates and nucleophiles to give highly decorated furans in good yield. The process is mild and can lead to the formation of a fragile, biologically-relevant epoxyfuran motif. The complementary nature of the thioether catalysis with other organocatalyzed processes has allowed the reaction to be incorporated into a three-component domino sequence.

The Synthesis of Azadirachtin: A Potent Insect Antifeedant

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.

Rhodium‐Catalyzed Domino Enantioselective Synthesis of Bicyclo[2.2.2]lactones

Once, twice, three times a catalyst! A novel domino rhodium(I)-catalyzed asymmetric transformation of substituted oxabicyclic alkenes into bicyclo[2.2.2]lactones proceeded with good yields (up to 78 %) and excellent stereoselectivity (>97 % ee; see scheme; cod=1,5-cyclooctadiene, Tf=trifluoromethanesulfonyl). Mechanistic investigations suggest that this process proceeds by rhodium-catalyzed asymmetric ring opening, allylic alcohol isomerization and oxid

Enantioselective synthesis of (+)-petromyroxol, enabled by rhodium-catalyzed denitrogenation and rearrangement of a 1-sulfonyl-1,2,3-triazole.

Petromyroxol is a nonracemic mixture of enantiomeric oxylipids isolated from water conditioned with larval sea lamprey. The (+)-antipode exhibits interesting biological properties, but only 1 mg was isolated from >100 000 L of water. Recently, transition-metal-catalyzed denitrogenation of 1-sulfonyl-1,2,3-triazoles has emerged as a powerful strategy for the synthesis of value-added products, including efficient diastereocontrolled construction of tetrahydrofurans. This methodology enabled the rapid development of the first synthesis of (+)-petromyroxol in 9 steps and 20% overall yield from a readily accessible starting material.

Synthesis of cyclopropyl-substituted furans by brønsted Acid promoted cascade reactions.

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction.

Second‐Generation Synthesis of Azadirachtin: A Concise Preparation of the Propargylic Mesylate Fragment

A second bite of the apple: A new and highly efficient synthesis of the propargylic mesylate fragment of azadirachtin has been accomplished (see scheme; Bn = benzyl, Ms = methanesulfonyl, PMB = para-methoxybenzyl, TBDPS = tert-butyldiphenylsilyl). An enantioselective catalytic hetero Diels-Alder reaction sets up the stereocenter at C15, which then controls the installation of the remaining functionality in a total of only 17 steps.