Lessons in Strain and Stability: An Enantioselective Synthesis of (+)-[5]-Ladderanoic Acid.

The synthesis of structurally complex and highly strained natural products provides unique challenges and unexpected opportunities for the development of new reactions and strategies. Herein, the synthesis of (+)-[5]-ladderanoic acid is reported. En route to the target, unusual and unexpected strain-release driven transformations were uncovered. This required a drastic revision of the synthetic design that ultimately led to the development of a novel stepwise cyclobutane assembly by allylboration/Zweifel olefination.

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