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The presence of a quaternary centre--a carbon with four other carbons bonded to it--in any given molecule can have a substantial chemical and biological impact. In many cases, it can enable otherwise challenging chemistry. For example, quaternary centres induce large rate enhancements in cyclization reactions--known as the Thorpe-Ingold effect--which has application in drug delivery for molecules with modest bioavailability.sup.1. Similarly, the addition of quaternary centres to a drug candidate can enhance both its activity and its metabolic stability.sup.2. When present in chiral ligands.sup.3, catalysts.sup.4 and auxiliaries.sup.5, quaternary centres can guide reactions toward both improved and unique regio-, stereo- and/or enantioselectivity. However, owing to their distinct steric congestion and conformational restriction, the formation of quaternary centres can be achieved reliably by only a few chemical transformations.sup.6,7. For particularly challenging cases--for example, the vicinal all-carbon.sup.8, oxa- and aza-quaternary centres.sup.9 in molecules such as azadirachtin.sup.10,11, scopadulcic acid A.sup.12,13 and acutumine.sup.14--the development of target-specific approaches as well as multiple functional-group and redox manipulations is often necessary. It is therefore desirable to establish alternative ways in which quaternary centres can positively affect and guide synthetic planning. Here we show that if a synthesis is designed such that each quaternary centre is deliberately leveraged to simplify the construction of the next--either through rate acceleration or blocking effects--then highly efficient, scalable and modular syntheses can result. This approach is illustrated using the conidiogenone family of terpenes as a representative case; however, this framework provides a distinct planning logic that is applicable to other targets of similar synthetic complexity that contain multiple quaternary centres. An approach in which quaternary centres are leveraged to improve synthetic planning can lead to shorter and optimized syntheses, demonstrated here on a series of polycyclic terpenes., Author(s): Pengfei Hu [sup.1] , Hyung Min Chi [sup.1] , Kenneth C. DeBacker [sup.1] , Xu Gong [sup.1] , Jonathan H. Keim [sup.1] , Ian Tingyung Hsu [sup.1] , Scott [...]