Intramolecular [4 + 4] photoreaction of 2-pyrones with a 1,3-enyne yields an unstable 1,2,5-cyclooctatriene product. Without a C4 pyrone substituent, 1,3-hydrogen migration converts the allene to a 1,3-diene, with a skeleton related to dactylol. With methoxy substitution, Cope rearrangement yields a nine-membered ring fused to a cyclobutane. Both structures were confirmed by X-ray crystallography. The Cope rearrangement is apparently reversible, reforming the allene which undergoes a proton shift to the more stable 1,3-diene product.

Benzene is unreactive as a photochemistry partner with 2-pyridone, however benzene substitution can allow for an efficient [4+4] (a k a, ‘para’) photocycloaddition. Productive substituents include alkoxy, cyano, ester, and trifluoromethyl, suggesting that inductively electron-withdrawing groups are sufficient, however a single fluorine substituent does not result in cycloaddition. When the product of this cycloaddition contains a conjugated system (e.g., an unsaturated ester) a secondary photocycloaddition can follow, forming triply bridged all-syn-[3]ladderane products.

Reactive 1,2,5-cyclooctatrienes, formed by photocycloaddition of 2-pyridones with enynes, are stabilized by steric shielding, slowing or preventing an otherwise facile [2 + 2]-dimerization reaction. Diisopropylsilyl ether-tethered reactants paired with an alkene substituent (R) produce allenes that are stable (R = TMS) or that isomerize to 1,3-dienes by hydrogen migration (R = alkyl). Under acidic conditions, hydrolysis of the photoproduct’s silyl ether can lead to a [3,3]-sigmatropic rearrangement.

Homopolymers of β-lactams can be grown by surface-initiated polymerization. These surface-linked β-peptides are living polymers with the potential to be utilized as tunable, protease-resistant interfaces in multiphase structural composites where the characteristics of the interface influence bulk properties.

Silanediol peptidomimetics are demonstrated to inhibit a serine protease. Asymmetric synthesis of the inhibitor was accomplished using Brown hydroboration and CBS reduction of an acylsilane intermediate. The silanediol product was found to inhibit the serine protease chymotrypsin with a Ki of 107 nM. Inhibition of the enzyme may involve exchange of a silane hydroxyl with the active site serine nucleophile, contrasting with previous silanediol protease inhibitors.

An amino acid carrying a 1-(4-dihydroxymethylsilyl)butyl side chain has been prepared in enantiomerically pure form as a potential inhibitor of the enzyme arginase, a pharmaceutical target. As a water-soluble silanediol, this compound was anticipated to be entropically stabilized against polymerization and siloxane formation. At 50 mM in D2O, the degree of oligomerization was found to be pH dependent, with diastereomeric mixtures formed on condensation. Above pH 11 the silane is largely monomeric.

A five-step assembly of silicon-protected dipeptide mimics from commercially available reagents is described. This methodology makes silanediol protease inhibitors readily available for the first time. The sequence features asymmetric hydrosilylation, a novel reduction of a silyl ether to a silyllithium reagent, and addition of this dianion to a sulfinimine, to produce the complete inhibitor skeleton with full control of stereochemistry. Oxidation of the primary alcohol to an acid completes the synthesis.

Enyne photocycloaddition with a 2-pyridone yields a mixture of products including amide-bridged 1,2,5-cyclooctatrienes, the first examples of enyne [4 + 4] adducts. Four regio- and stereochemical isomers of the [4 + 4] adduct are possible. All appear to be too strained to be isolated, but they have been identified as their [2 + 2] cyclobutane dimers. Cyclobutane and cyclobutene adducts have also been isolated, [2 + 2] addition products possibly related to the unstable [4 + 4] adducts via Cope rearrangement. Calculations suggest that [3,3] rearrangements have high energy barriers, however, making thermal interconversion unlikely.

Intramolecular [4 + 4] photocycloaddition of a furan and a cyclopentane-annulated 2-pyridone yields a cyclooctadiene product with four new stereogenic centers. Transannular ring closure produces the 5−5−5−5 fused ring system of the crinipellins, including three contiguous quaternary carbons, with the correct absolute stereochemistry derived from (−)-carvone.

An approach to assembling unsymmetrically coupled piperidines is described, involving initial [4 + 4] photocycloaddition of 2-pyridones, followed by Cope rearrangement and retro-Mannich reaction. In these reactions, four stereogenic centers set during cycloaddition are relayed or erased during the subsequent steps. Two methods for retro-Mannich reaction are demonstrated.

Four diastereomers of a Phe-Ala peptide mimic incorporating a central silanediol group have been individually prepared and tested as inhibitors of angiotensin-converting enzyme (ACE). Three of the silanediols exhibit levels of inhibition that are similar to those of corresponding ketones reported by Almquist. For the fourth diastereomer, with both stereogenic carbons inverted relative to the most active isomer, the ketone gives the least enzyme inhibition whereas the silanediol shows a surprisingly low IC50 value.Four diastereomers of a Phe-Ala peptide mimic incorporating a central silanediol group have been individually prepared and tested as inhibitors of angiotensin-converting enzyme (ACE). Three of the silanediols exhibit levels of inhibition that are similar to those of corresponding ketones reported by Almquist. For the fourth diastereomer, with both stereogenic carbons inverted relative to the most active isomer, the ketone gives the least enzyme inhibition whereas the silanediol shows a surprisingly low IC50 value.

Homopolymers of β-lactams can be grown by surface-initiated polymerization. These surface-linked β-peptides are living polymers with the potential to be utilized as tunable, protease-resistant interfaces in multiphase structural composites where the characteristics of the interface influence bulk properties.

Polycyclic aromatics undergo [4 + 4] photocycloaddition to give substituted cyclooctadiene products. We have examined the [4 + 4] photoreactivity of these aromatics with enynes using a recently developed substitution pattern that undergoes a 1,3-hydrogen migration, forming a single cycloadduct. Several substrates yield stable, isomerized [4 + 4] adducts.

Correction for ‘Enyne [4 + 4] photocycloaddition with polycyclic aromatics’ by Buddha B. Khatri et al., Org. Chem. Front., 2014, 1, 961–964.