1. Organic Pedagogical Electronic Network An Introduction to Catalytic Nitrene C–H Oxidation Ashley M. Adams, Justin Su, And J. Du Bois

2. Nitrenes & Nitrenoids 1. Acc. Chem. Res. 1987, 20, 18-27. 2.For general reviews, see: a) Chem. Rev. 2008, 108, 3379-3394. b) Catalyzed Carbon-Heteroatom Bond Formation; Weinheim, 2011; pp 137-156. c) Chem. Commun. 2009, 5061–5074. d) Top. Curr. Chem., 2010, 292, 347-378. e) Acc. Chem. Res. 2012, 45, 911-922. Electron deficient with only six valence electrons (analogous to carbenes); hyper-reactive 1 Can be generated through thermal or photochemical extrusion of N 2 from organoazides Nitrene reactivity can be tempered through association with certain metal complexes The use of dirhodium complexes is particularly effective for nitrenoid formation Nitrenes NitreneCarbene Nitrenoids (aka a metal-bound nitrene) Examples include:

3. Rh-Catalyzed C–H Amination 1.Angew. Chem. Int. Ed. 2001, 40, 598-600; J. Am. Chem. Soc. 2004, 126, 15378–15379. 2.J. Am. Chem. Soc. 2009, 131, 7558-7559. 3.Tetrahedron, 2009, 65, 3042-3051 Reaction initiates with condensation of carbamate or sulfamate and PhI(OAc) 2 to generate an iodoimine  Modern methods for nitrenoid C–H amination can be used to generate heterocyclic products  Reactions rely on catalytic amounts of dirhodium complex and an iodine(III) oxidant Iodoimine coordination to dirhodium catalyst results in Rh-nitrene formation Step 1: Step 2: Step 3: Nitrenoid C–H insertion

4. Reaction Selectivity 1.Modern Rhodium-Catalyzed Organic Reactions, Ed.: P. A. Evans, Wiley-VCH Verlag, Weinheim, 2005, 379-416 2.Org. Lett. 2003, 5, 4823-4826; Angew. Chem. Int. Ed 2009, 48, 2777-2779; Tetrahedron 2009, 65, 3042-3051, Choice of functional group alters selectivity between 5- and 6-membered ring formation Competition between different C–H bond types favors 3° and benzylic C–H bonds Tces = S(O) 2 OCH 2 CCl 3 Despite intrinsic reactivity differences, choice of metal catalyst can alter C–H bond selectivity

5. Suggested Problems 1.J. Am. Chem. Soc. 2003, 125, 11510-11511 2.Angew. Chem. Int. Ed 2009, 48, 2777-2779 1. Predict the product for the following reaction en route to the complex natural product (−)-tetrodotoxin, the poisonous constituent of the puffer fish. 2. Provide two stereochemical models to rationalize the following results: 3. Oxidative cyclization of substrate A gives a single, major product as shown. Conversely, reaction of a 1:1 mixture of substrates B and C give a 1:1 mixture of the corresponding heterocyclic products. Provide a mechanistic rationale for these disparate results.