Vitamin D (1, VitD) was identified in the early 20 th century as one of the essential molecules of the diet to support human life. A deficiency of VitD3 (4, Figure ) can result in a range of maladies such as a weakened immune system, rickets and osteomalacia. The structure of VitD3 was first elucidated by Windaus and Thiele in 1936 building on the findings of Askew et al. who demonstrated that VitD2 (5) could be derived from irradiation of ergosterol. Radiolabeling studies established the most active form of VitD in the body to be calcitriol (6). From 1965-1975, foundational pharmacological studies established the basic role that VitD plays in regulating serum calcium and phosphorus and bone homeostasis. Critically, VitD is also implicated in a number of biological processes specifically through the regulation of the transcription of hundreds of genes in a cell-specific fashion. As a consequence, starting in the 1950's, an enormous amount of effort was expended by medicinal chemists to search for VitD analogs that could exhibit prodifferentiating and antiproliferative effects on normal and cancer cells as well as immunomodulatory effects without causing hypercalcemia. Such programs resulted in the synthesis of >3000 modified VitD analogs and the commercial launch of about a dozen new medicines (e.g. Hectorol, Zemplar, Calcijex, Rocaltrol). Calcipotriol (7, Dovonex TM , LEO Pharma) is currently the most successful VitD analog and is prescribed for the treatment of psoriasis, an autoimmune skin disease. To date, the majority of approaches to access VitD derivatives (1) have utilized a convergent assembly of an A-ring fragment (2) with a fully formed CD bicycle (3, including the side-chain). As the side-chain appears to play a critical role in modulating bioactivity this results in very lengthy medicinal chemistry routes. The case study from LEO Pharma depicted in Figure is emblematic of this challenge. Thus, in order to explore a simple aryl side-chain substituent, it must be tediously stitched onto the bicyclic aldehyde (8) [derived from degradation of VitD2 (5)], followed by coupling to the A-ring thereby severely limiting accessible chemical space. The goal of this study was two-fold: (1) design an enantioselective, scalable, and convergent approach to 7 not wedded to semisynthesis; and (2) use of such a platform to create known and novel VitD analogs in a modular fashion (such as 1). Extensive explorations from both academic and industrial arenas in this area provided a useful foundation for this study and set the stage for a completely unique approach. In this Article, the realization of the plan outlined in Figure through the strategic application of radical retrosynthesis for both ring annulation and substitution to address the CD rings, as well as symmetry recognition to scalably access 8 ring A is described. This convergent approach enables late-stage side-chain installation onto triene 9 (a stable precursor to VitD analogs) prepared via the union of fully formed A-ring (10) and CD ring (11) fragments derived from inexpensive materials (p-cresol and cyclohexanone, respectively).