The factors that influence the stereocontrol of trimethylenemethane (TMM) cycloadditions are examined in the context of a synthesis of a perhydroazulene. The diastereofacial selectivity with respect to the acceptor is established in an intramolecular [3 + 2] reaction with a five-carbon tether. When a doubly activated acceptor is utilized, complete selectivity is observed wherein the Z-situated activating group is proposed as a diastereoselectivity control element. Further, the use of trimethylstannyl acetate as a cocatalyst for cycloadditions to electron deficient alkenes is illustrated for the first time, A one-pot, three-component coupling protocol provides a facile new entry into acyl-substituted TMM precursors specifically and a-hydroxy ketones more generally. The methodology led to a total synthesis of (-)-isoclavukerin A. The shortest version of the synthesis involves eleven steps from methallyl alcohol.