A general synthetic strategy featuring a diastereoselective intramolecular Pauson–Khand reaction (IPKR) and some tactical synthetic manoeuvres to access ten iridoids in a stereocontrolled manner is delineated.

Experimental 13C kinetic isotope effects (KIEs) and density functional theory (DFT) calculations are used to evaluate the mechanism and origin of enantioselectivity in the formal C­(sp2)–H alkylative desymmetrization of cyclopentene-1,3-diones using nitroalkanes as the alkylating agent. An unusual combination of an inverse (∼0.980) and a normal (∼1.033) KIE is observed on the bond-forming carbon atoms of the cyclopentene-1,3-dione and nitroalkane, respectively. These data provide strong support for a mechanism involving reversible carbon–carbon bond formation followed by rate- and enantioselectivity-determining nitro group elimination. The theoretical free-energy profile and the predicted KIEs indicate that this elimination event occurs via an E1cB pathway. The origin of remote stereocontrol is evaluated by distortion–interaction and SAPT0 analyses of the E1cB transition states leading to both enantiomers.

Ladderane phospholipids, with their unusual ladder-like arrangement of concatenated cyclobutane rings, represent an architecturally unique class of natural products. However, despite their fascinating structure and other necessary impetus, only a few synthetic studies of these molecules have been reported so far. We have now devised a concise total synthesis of [3]-ladderanol, a component of natural ladderane phospholipids, using an organocatalytic enantioselective desymmetrizing formal C(sp 2 )À H alkylation. Our synthetic strategy rests on the late-stage introduction of chirality, thus allowing facile access to both enantiomers of [3]-ladderanol as well as an analogue. This is the first time a desymmetrization strategy is applied to the synthesis of [3]-ladderanol. The scope of this desymmetrizing C(sp 2 )À H alkylation of meso-cyclobutane-fused cyclohexenediones is also presented.

Ladderane phospholipids, with their unusual ladder‐like arrangement of concatenated cyclobutane rings, represent an architecturally unique class of natural products. However, despite their fascinating structure and other necessary impetus, only a few synthetic studies of these molecules have been reported so far. We have now devised a concise total synthesis of [3]‐ladderanol, a component of natural ladderane phospholipids, using an organocatalytic enantioselective desymmetrizing formal C(sp2)−H alkylation. Our synthetic strategy rests on the late‐stage introduction of chirality, thus allowing facile access to both enantiomers of [3]‐ladderanol as well as an analogue. This is the first time a desymmetrization strategy is applied to the synthesis of [3]‐ladderanol. The scope of this desymmetrizing C(sp2)−H alkylation of meso‐cyclobutane‐fused cyclohexenediones is also presented.

Ladderane phospholipids, with their unusual ladder-like arrangement of fused cyclobutane rings, represent an architecturally unique class of natural products. However, despite their fascinating structure and other necessary impetus, only a few synthetic studies of these molecules have been reported so far. We have now devised a concise synthesis of [3]-ladderanol, a component of ladderane phospholipids, using an organocatalytic enantioselective desymmetrizing formal C(sp2)‒H alkylation. Our synthetic strategy rests on a late-stage introduction of chirality, thus allowing facile access to both the enantiomers of [3] ladderanol as well as its analog. This is the first time a desymmetrization strategy is applied to the synthesis of [3]-ladderanol. The scope of this desymmetrizing C(sp2)‒H alkylation of meso cyclobutane fused cyclohexenediones is also presented.