With fragments 4 and 5 in hand, we turned our attention to their union through a stereocontrolled lithiationborylation reaction. Before embarking on this key C-C bond forming reaction we wanted to explore what level of substrate control might be imparted by the neighbouring 6-ring acetonide moiety in TIB ester 5. Previously, Hoppe reported that the 5-ring acetonide in carbamate 30 exerted strong control over stereoselectivity in the deprotonation with s BuLi in the absence of diamine ligands (Scheme 3A). However, our attempts at a diaminefree lithiation-borylation using model acetonide-containing TIB ester 25 and boronic ester 32 were unsuccessful due to the failure of 25 to deprotonate under these conditions (Scheme 3B). We attribute this contrasting reactivity to the weaker complexation of s BuLi to the 6-membered acetonide in 25 compared to the 5-membered acetonide in 30. Hoppe found that substrate control in the deprotonation of 30 could be largely overridden with diamine ligands, including TMEDA and sparteine. Fortunately, we found that addition of TMEDA enabled the coupling of 25 and 32 to proceed in excellent yield. Using TMEDA the diastereoselectivity was low, indicating no substrate-control, but using (+)-or (-)-sparteine enabled either diastereoisomer of 33 to be obtained with high selectively. Further studies by ReactIR revealed that deprotonation of 25 was exceptionally fast (t1/2 deprotonation ~2 min at -78 °C) and that borylation was essentially instantaneous with primary boronic ester 32. Scheme 3. Study of Effects of Substrate Control on Asymmetric Lithiation.