Deacylative diazo transfer

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. 

Preparative Method by the reaction of 2,4-dimethyl-3-pentanol with diketene followed by methylation and deacylative diazo transfer. ... 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

Two strategies have been developed for the preparation of esters of diazoacetic acid. If the alcohol is inexpensive, it is first converted (diketene) into the corresponding acetoacetate (120 equation 49). Diazo transfer with subsequent deacylation then yields the diazoacetate (121). If the alcohol is particularly valuable or sensitive, it may alternatively be esterified with a more direct precursor to diazoacetate. One reagent that has been used for this purpose is glyoxalic acid 2,4,6-triisopropylbenzenesulfonylhydrazone (TIPPS) (123 equation 50). Esterification of the alcohol (122) with (123), using dicyclohexylcarbo-diimide followed by addition of 4-dimethylaminopyridine, gives the diazoacetate (124). ... 

As with diazo ketones, an a-diazo ester (126) can be prepared by nitrosation of the corresponding a-amino acid (125) or a derivative (equation 51). Alternatively, an a-diazo ester (128) can be prepared by diazo transfer to an alkylated acetoacetate (127), with concomitant deacylation (equation 52). ... 

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