Synthesis of ethyl 1,3,6-trioxaspiro[4.5]Decane-4-carboxylate derivatives from δ-lactones [preparation of 2-methoxy-2-glycolamide-tetrahydro-2h-pyran; elaboration of pederamide side-chain]

✍ Scribed by Angelina J.Duggan; Michael A. Adams; Jerrold Meinwald

• Book ID: 104246239
• Publisher: Elsevier Science
• Year: 1978
• Tongue: French
• Weight: 206 KB
• Volume: 19
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)95215-3

✦ Synopsis

In a preceding communication we reported the preparation of hemiketals by the addition of lithium ester enolates to the carbonyl groups of d-lactones and y-lactones.

1,2 Herein, we describe the utility of these derivatives in the synthesis of 1,3,6-trioxaspiro[4.5]decanes which can be transformed into substituted glycolamides, synthons for molecules related to pederamide. 3

We have observed that lithium ethyl O_(P-methoxy-2-propyl)glycolate (2j4 reacts with &valerolactone at -75'C in THF to generate hemiketal 3 in 71% yield.' Since the alcohol protecting group derived from isopropenyl methyl ether is extremely labile,5 the hemiketal 3 is converted in 90% yield to the a-hydroxy hemiketal 46 within minutes at ambient temperature in THF-dilute acid.