A hydrogen borrowing reaction employing secondary alcohols and Ph* (MeC) ketones to give β-branched carbonyl products is described (21 examples). This new C-C bond forming process requires low loadings of [Cp*IrCl], relatively low temperatures, and up to 2.0 equiv of the secondary alcohol. Substrate-induced diastereoselectivity was observed, and this represents the first example of a diastereoselective enolate hydrogen borrowing alkylation. By utilizing the Ph* group, the β-branched products could be straightforwardly cleaved to the corresponding esters or amides using a retro-Friedel-Crafts reaction. Finally, this protocol was applied to the synthesis of fragrance compound (±)-3-methyl-5-phenylpentanol.

Spirocyclic oxindoles undergo an enantioselective oxygenation reaction (nine examples; e.r. up to 97:3) upon catalysis by a chiral ruthenium porphyrin complex (1 mol %). The catalyst exhibits a lactam ring, which is responsible for substrate association through hydrogen bonds, and an active ruthenium center, which is in a defined spatial relationship to the oxygenation substrate. DFT calculations illustrate the perfect alignment of the active site with the reactive C-H bond and suggest--in line with the kinetic isotope effect--an oxygen rebound mechanism for the reaction.

An iridium catalyzed method for the synthesis of functionalized cyclohexanes from methyl ketones and 1,5-diols is described. This process operates by two sequential hydrogen borrowing reactions, providing direct access to multisubstituted cyclic products with high levels of stereocontrol. This methodology represents a novel (5 + 1) strategy for the stereoselective construction of the cyclohexane core.

The application of an iridium-catalyzed hydrogen borrowing process to enable the formation of α-branched ketones with higher alcohols is described. In order to facilitate this reaction, ortho-disubstituted phenyl and cyclopropyl ketones were recognized as crucial structural motifs for C-C bond formation. Having optimized the key catalysis step, the ortho-disubstituted phenyl products could be further manipulated by a retro-Friedel-Crafts acylation reaction to produce synthetically useful carboxylic acid derivatives. In contrast, the cyclopropyl ketones underwent homoconjugate addition with several nucleophiles to provide further functionalized branched ketone products.

Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include 1) synthesis of the C1–C9 pyran core (5) using an AuCl3-catalysed cyclisation; 2) formation of C10–C22 vinyl iodide (55) by sequential bidirectional Stille reactions and 3) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (d.r.=91:9 at C9). The common callipeltoside aglycon (4) was completed in a further five steps. Following this, all three sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR spectrum of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2).