REGITZ Diazo transfer

R = aryl, alkyl, 0-alkyl, 0-aryl, NH2, NR2 R = Me, p-tolyl, p-C02H-phenyl R = alkyl, aryl R = H, alkyl, aryl base piperidine, NEts, HNEt2, KOEt, KOH solvent MeOH, EtOH, EtOH-H20, Et20, CH2CI2, CHCI3, acetonitrile 

In the laboratory of A. Padwa, a novel synthetic approach to the fully functionalized core of lysergic acid was developed utilizing an intramolecular isomunchone cycloaddition pathway. The key cycloaddition precursor diazo imide was prepared using the standard Regitz diazo tranter conditions. The diazo imide then was heated with catalytic amouts of rhodium(ll)-perfluorobutyrate in dichloromethane to afford the desired cycloadduct as a single diastereomer and in excellent yield. The only reason the authors were not able to complete the total synthesis of lysergic acid was that they could not affect the isomerization of the double bond between the two six-membered rings. 

A versatile stereoselective synthesis of endo,exo-furofuranones was accomplished by R.C.D. Brown and coworkers. One of the key steps was a Rh(ll)-catalyzed C-H insertion reaction and the required diazo lactone was prepared via the Regitz diazo transfer reaction. The 2-acetyl substituted lactone substrate proved to be recalcitrant toward the deacylative diazo transfer under standard conditions. Eventually the authors decided to use the very reactive triflyl azide (TfNs), which was generated in situ under phase-transfer conditions to afford the desired a-diazo lactone. The C-H insertion product was then converted to (+)-methylxanthoxylol. 

The carbocyclic [6-7] core of guanacastepenes was prepared by. D. Trauner et al. using the intramolecular reaction between carbenoids derived from diazo carbonyl compounds and furans. The required diazo carbonyl substrate was synthesized using p-acetamidobenzenesulfonyl azide (p-ABSA) as the diazo-donor component in the Regitz diazo transfer reaction. 

---

The reaction sequence is called the Regitz diazo transfer and requires active methylene compounds as substrates/ Hence it is common to use formic esters to create P-carbonyl compounds from ketones or aldehydes in an aldol reaction. These are used as substrates for deformy-lative diazo transfer reactions in which the diazo group is transferred and the formyl group is removed in one concerted step. The mechanism of the deformylative diazo transfer is shown below. In this case the bulky base NaHMDS ensures deprotonation at the less-hindered a-position of 3, forming the so-called kinetic enolate 13. This enolate is formylated by ethyl formate yielding the P-formyl ketone 14, which is used as substrate in the deformylative diazo transfer. 

P-keto ester a-diazo-P-keto ester Regitz diazo transfer... 

Regitz diazo transfer reactions have been reviewed previously.1-3 The following two main routes have been known for the synthesis of diazo compounds (1) diazotization of amines, oximes, nitrosoamines, and hydrazones (2) transfer of the diazo function from tosyl or mesyl azides to active methylene compounds. 

Other references related to the Regitz diazo transfer are cited in the literature. ... 

---