This Chemical Reaction Is Literal Magic & You Never Heard Of It

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If there is a chemistry cheat code, this reaction might be it. In this video, we explain the theoretical grounds and practical applications of dyotropic reactions. In these rearrangements, two sigma bonds migrate simultaneously or "swap places". This first part will involve some time travel, discussion of the infamous Woodward-Hoffmann rules and discovery of strange paper footnotes. In the second part, we discover how these reactions facilitated a synthesis of a cancer-killing worm molecule - because why not.

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00:00 Your teacher HATES this simple chemistry trick
01:27 PART 1: Steroids, fertile grounds for many chemistry insights
02:39 Dyotropic reaction mechanism, Manfred Reetz and type I dyotropic reactions
04:10 Entering the rabbit hole: Woodward-Hoffmann
05:14 Conservation of orbital symmetry, orbital diagrams and symmetry operations
07:02 Allowed reaction (Diels-Alder) and "forbidden" reaction ([2+2] addition)
09:35 How can you achieve your learning goals better and faster?
11:19 A shortcut to symmetry-allowed vs. symmetry-forbidden reactions
14:05 Exiting the rabbit hole: How do we categorize sigma-bond migrations?
15:31 Why do forbidden reactions occur? Secondary orbital effects
17:22 Type II dyotropic reactions, and visiting an old friend
19:02 Where to find free organic chemistry practice problems
19:18 Dyotropic reactions in nature
20:35 PART 2: 160kg of Cephalodiscus worms, and shark alarm
21:55 Structure-activity relationship in cephalostatins
23:25 Why we need total synthesis of natural products
25:17 Synthesis A: "Brute force"
26:10 Synthesis B: "Dyotropic elegance"
29:27 Many stories end without a happy end

Key publications:
PART 1: DYOTROPIC REACTIONS
Monatsh. Chem. 1906, 27, 421 | Neue Beiträge zur Kenntnis des Cholesterins
Helvetica Chimica Acta 1952, 35, 782 | Mechanismus der Mutarotation von 5,6-Dibromcholestan
Angew. Chem. Int. Ed. 1972, 11, 129 | Dyotropic Rearrangements, a New Class of Orbital-Symmetry Controlled Reactions. Type I
Tetrahedron 1973, 29, 2189 | Primary and secondary orbital effects in dyotropic rearrangements
Angew. Chem. Int. Ed. 1969, 8, 781 | The Conservation of Orbital Symmetry
Adv. Organomet. Chem. 1977, 16, 33 | Dyotropic Rearrangements and Related σ-σ Exchange Processes
Helvetica Chimica Acta 1972, 55, 67 | The Stabilization of Bridged Structures of Ethanes
Chem. Rev. 2009, 109, 6687 | Dyotropic Reactions: Mechanisms and Synthetic Applications
Chem. Eur. J. 2006, 12, 6323 | Stereoelectronic Effects on Type I 1,2-Dyotropic Rearrangements in Vicinal Dibromides
Angew. Chem. Int. Ed. 1972, 11, 130 | Dyotropic Rearrangements, a New Class of Orbital-Symmetry Controlled Reactions. Type II
PART 2: CEPHALOSTATIN
J. Am. Chem. Soc. 1988, 110, 2006 | Antineoplastic agents. Isolation and structure of the powerful cell growth inhibitor cephalostatin
J. Nat. Prod. 2015, 78, 1446 | The Cephalostatins. Isolation, Structure, and Cancer Cell Growth Inhibition of Cephalostatin 20
J. Am. Chem. Soc. 1998, 120, 692 | Interphylal Product Splicing:  The First Total Syntheses of Cephalostatin 1, the North Hemisphere of Ritterazine G, and the Highly Active Hybrid Analogue, Ritterostatin GN1N
Chem. Rev. 2009, 109, 2275 | Chemistry of Trisdecacyclic Pyrazine Antineoplastics: The Cephalostatins and Ritterazines
J. Am. Chem. Soc. 2002, 124, 4548 | Dyotropic rearrangement facilitated proximal functionalization and oxidative removal of angular methyl groups: efficient syntheses of 23'-deoxy cephalostatin 1 analogues

Some recommended books on organic synthesis:
Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
Nicolaou; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)