The thiopyran route to polypropionates. Asymmetric synthesis of the building blocks by enantioselective protonation

A highly efficient method for solvent‐free synthesis of bisarylmethylidenes of pyranones and thiopyranones

“…In addition, substituted products of thiopyranone 2 are attractive as well since they could be converted via removal of sulfur atom to ␣,␤-unsaturated ketones which are not easily prepared by direct standard procedures [4]. The strategy to use such skeletons for construction of various synthetic targets is well established and has been recently demonstrated by Ward et al for the synthesis of polypropionate building blocks [5].…”

The thiopyran route to polypropionates

“…Reaction of the lithium anion of N,Ndimethylhydrazone 38 with 37 followed by hydrolysis of the hydrazone produced a 1 : 1.6 mixture of 39 and the desired 40, respectively. RANEY s nickel desulfurization of the desired 40 gave the volatile serricornin (41) in moderate yield.…”

“…The enantioselective preparation of (S)-(À)-54 is illustrated in Scheme 11. 41 Thiol ester (AE)-63 was obtained in three steps from 3 in excellent yield without need for chromatography. Reaction of (AE)-63 with s BuLi followed by enantioselective protonation 42 of the resulting lithium enolate with (À)-64 43 at low temperature gave (+)-63 (er 8-10 : 1) in near quantitative yield.…”

“…The reaction of 5 with (S)-(À)-54 (er > 35 : 1) as described in Table 1 (entries 2-5) provided (À)-55as, (+)-55ss, (À)-55sa, and (À)-55aa with high enantiomeric purities (er >30 : 1) (Scheme 10); 45 the enantiomers are similarly available using (R)-(+)-54 prepared as shown in Scheme 11 but using (+)-ent-64. 41 Using the conditions established for diastereoselective aldol reactions of 5 with 54, reactions with aldehydes (AE)-60a and (AE)-60b were examined (Scheme 12; Table 2). In keeping with Evans' model for additions to related acyclic 3-alkoxy-2methyl aldehydes, 46 the cis aldehyde (AE)-60a gave both Felkin (65as, 65ss) and non-Felkin adducts (65sa, 65aa) with low diastereoselectivity under non-chelating conditions (entries 1 and 2) but the non-Felkin adducts were formed exclusively with moderate diastereoselectivity under chelating conditions (entry 3).…”

An Efficient and Improved Method for the Synthesis of Bis(arylmethylidene)thiopyranones

“…3 The strategy to use thiopyran skeletons for the construction of various synthetic targets is well established and has been recently demonstrated by Ward et al for the synthesis of polypropionate building blocks. 4 The crossed aldol condensation has been employed for the synthesis of bis(arylmethylidene)cycloalkanones by the reaction of homocyclic ketones with aromatic aldehydes. 5 Many developments have been achieved in recent years to widen the synthetic scope of bis(arylmethylidene)cycloalkanones by optimizing the reaction temperature, reaction time, and product yield.…”