Guang Yu Fang

Asymmetric Synthesis of Allylsilanes by the Borylation of Lithiated Carbamates: Formal Total Synthesis of (−)-Decarestrictine D†

Chiral allylsilanes are highly valuable nucleophiles in stereoselective organic synthesis because of the multitude of asymmetric transformations that they can undergo. For example, b-hydroxy allylsilanes have been used extensively by the groups of both Panek and Roush in natural product synthesis. Amongst the most useful applications in recent years are the [3+2] annulation and the [4+2] annulation as they allow facile access to furans and pyrans. However, the synthesis of substituted b-hydroxy allylsilanes is not always straightforward and usually requires multiple steps. The broad synthetic utility of b-hydroxy allylsilanes motivated us to develop more efficient synthetic routes to such intermediates. We recently reported a new method for the homologation of boronic esters and boranes by employing the lithiated carbamates reported by Hoppe et al. Our method involved the use of carbamates derived from primary and secondary alcohols, which led to the formation of secondary and tertiary alcohols in high enantiomeric ratios after oxidation. The reaction could be extended to a one-pot, multiple homologation process and its application in the synthesis of (+ )-faranal was demonstrated. In extending this methodology further, we considered its application in the stereocontrolled, one-pot synthesis of b-hydroxy allylsilanes. We envisioned that the reaction of a lithiated carbamate with bsilyl vinyl borane 3 would form the intermediate allylborane 5 which could react with an aldehyde to give an Zconfigured anti-allylsilane 7 (Scheme 1). Subsequent epoxidation and elimination/ring-opening could then provide a stereocontrolled route to 2-ene-anti-1,4-diols 9, a common motif in natural products (Scheme 1). Herein we detail our success in developing this methodology and its application in synthesis. Our initial studies, however, revealed some unexpected results (Scheme 2). For example, the reactions of lithiated carbamates 2a,b with B-Ph-9-BBN and subsequent oxidation gave the corresponding alcohols 11a,b in 97:3 e.r. and with complete retention of configuration. Surprisingly, reaction of the lithiated carbamate 2b with borane 3 and subsequent trapping with benzaldehyde gave allylsilane 7b in only 71:29 e.r. More alarmingly, lithiated carbamate 2a gave allylsilane ent-7a in 93:7 e.r. but now with inversion of the expected stereochemistry. Through a careful set of control experiments we established that the recalcitrant step causing the unexpected selectivity was the reaction of the lithiated carbamate with the borane, and that the reaction was critically dependent upon the nature of the amine that was complexed to the lithiated carbamate. In our detailed studies we used the related stannane 12 since the stereochemistry associated with the synthesis of 12, its subsequent lithiation, and electrophilic trapping had been reported and rigorously proven by Hoppe et al. We first explored diamine-free reactions by initial formation of Scheme 1. Proposed synthesis of b-hydroxy allylsilanes 7 and anti-diols 9 ; Cb= N,N-diisopropylcarbamoyl, sp = ( )-sparteine, Cy = cyclohexyl.

Reactions of silyl-stabilised sulfur ylides with organoboranes: enantioselectivity, mechanism, and understanding

The reaction of trimethylsilyl-substituted sulfonium ylides with organoboranes (Ph(3)B, Et(3)B) has been studied and although homologated products were obtained in good yield (after oxidation to the corresponding alcohols), the enantiomeric excesses were low with our camphor-based chiral sulfide (up to 40% ee, cf. corresponding phenyl-substituted sulfonium ylides gave >95% ee). Cross-over experiments were conducted to ascertain the nature of this difference in selectivity. Thus, aryl- and silyl-substituted sulfonium ylides (1 equiv.) were (separately) reacted with Et(3)B (1.5 equiv.) followed by Ph(3)B (1.5 equiv.) The experiments were repeated changing the order of addition of the two boranes. It was found that the aryl-substituted sulfonium ylide only trapped the first borane that was added indicating that ate complex formation was non-reversible and so was the selectivity determining step. In contrast the silyl-substituted sulfonium ylide only trapped Ph(3)B (it is more reactive than Et(3)B) indicating that ate complex formation was reversible and so 1,2-migration was now the selectivity determining step. The reactions have been studied computationally and the experimental observations have been reproduced. They have further revealed that the cause of reversibility in the case of the silyl-substituted sulfonium ylides results from ate complex formation being less exothermic and a higher barrier to 1,2-migration.