Tandem Mukaiyama aldol lactonization

The zinc chloride-mediated tandem Mukaiyama aldol-lactonization reaction of aldehydes 21 and thiopyridylketene acetals 22 gave mainly the trans isomer 23. However, if the catalyst is stannic chloride and the reaction is carried out at -78 °C, then the cyclization is highly diastereoselective and yields the cis-isomer 24 <990L1197>. 

Diastereoselective /3-lactone formation was also carried out by a tandem Mukaiyama aldol lactonization between an aldehyde 132 and a thiopyridyl ketene acetal 133 (Equation 46) <2005CCL1448>. This reaction gave the /3-lactone 134 as a 10 1 (transacts) mixture of diastereoisomers and the major isomer was converted into (-)-tetrahydrolipstatin by silyl deptotection followed by a Mitsunobu coupling to form the ester. 

A highly diastereoselective, tandem Mukaiyama aldol-lactonization provides chiral... 

The synthetic utility of the Mukaiyama aldol reaction is broadened when coupled with other reactions in a tandem fashion. Romo and coworkers developed a highly diastereoselective tandem Mukaiyama aldol-lactonization... 

The p-lactone cyclization precursors come from Romo and Yang s tandem Mukaiyama aldol lactonization (TMAL) process (Scheme 7) [10]. As an example of this, lactone 25 was the product of the ZnCl2-mediated cyclization of a-benzyloxy aldehyde 24 with thio-ketene acetal 23. Ozonolytic cleavage of the alkene gave 26. 

Pyrid-2-yl congeners of the reagent have been employed for the synthesis of 8-lactones via a tandem Mukaiyama aldol lac-tonization (TMAL) process. Herein, choice of Lewis acid promoter (zinc(n) chloride or tin(IV) chloride) determines whether cis or trans 8-lactone products are obtained (eq 15). The analogous Mannich initiated sequence provides /3-lactams. ... 

---