A Butyrolactone → 1,3‐Diol Strategy for the Obtention of Tolypothrix Polyethers – Stereoselective Synthesis of a Key Lactone Precursor

Abstract

AbstractA novel access to 1,3,5,7,…︁‐polyols is developed. It follows – in the context of the planned synthesis of the natural permethylated 1,3,5,7,9‐pentaol 1a from the blue‐green alga Tolypothrix conglutinata – the strategy depicted in Scheme 4. The present paper concerns the enantioselective synthesis of the key building block syn‐9a. This γ‐lactone was derived from O‐tert‐butyldiphenylsilylglycidol (R−15) via a synthetic equivalent of the 6‐hydroxy‐4‐ketoester 12 (cf. Scheme 5). As such, we used the hydroxydiene 28 rather than the 2‐(5‐hydroxy‐3‐methylenepentyl)‐1,3‐oxazoline 26 or the (5‐hydroxy‐3‐methylenepentyl)‐substituted orthoester 27 because of its greater ease of preparation (cf. Scheme 7). A double ozonolysis of the hydroxydiene 28 provided the desired 6‐hydroxy‐4‐ketoester 12 itself (Scheme 8). The CO bond of this compound was reduced syn‐selectively (ds = 100:0) through successive additions of Et2B(OMe) and NaBH4 and anti‐selectively (ds = 80:20) through the addition of NaBH(OAc)3 (Scheme 9). The dihydroxy ester syn‐34 formed in the mentioned syn‐selective reduction was isolable or could be lactonized in the presence of acid so that the syn‐configured hydroxy lactone syn‐9a was obtained directly (Scheme 10).