Trost s reagent

From intermediate 12, the path to periplanone B (1) is short but interesting. Enolization of 12 with lithium bis(trimethylsilyl)amide at -78 °C, followed by sulfenylation using Trost s reagent,12 affords a 16 1 mixture of regioisomeric monosulfenylated ketones favoring intermediate 17. The regioselectivity displayed in this reaction is... 

Annulation to carbonyl functions has also been achieved with Trost s bifunctional reagents. Whereas the parent silyl acetate (97) yields only simple alkylation products with aldehydes under normal conditions, addition of only a few mole % of trimethyltin acetate to the reaction mixture results in facile formation of methylenetetrahydrofurans Furthermore, excellent diastereoselectivity is observed in the cycloaddition to a galactose-derived aldehyde (125) (equation 136). The tin acetate co-catalyst also promotes addition to relatively unreactive ketone carbonyls, such as in the case of benzofuran (126) and the acetylenic ketone (127) (equations 137, 138). It is remarkable that even the sterically hindered enone (128) reacts preferentially at the ketone function (equation 139). A tributyltin analog (129) of (97) has been used in the stepwise formation of a methylenetetrahydrofuran from aldehydes. Similarly, pyrrolidines can be prepared from the corresponding imines in two steps via a Lewis acid-catalyzed 1,2-addition of the tin reagent, which is then followed by a Pd-catalyzed cyclization (equation 140). Direct formation of pyrrolidine from the imine is possible if one uses a mesylate analog of (97) and a nickel(O) catalyst (equation 141). ... 

Next, process chemistry for the practical synthesis of 7b (MGS0028) is discussed (Schemes 3.5-3.7) [42-45]. First, the synthesis of key intermediate (+)-29 from racemic acetoxycyclopentene (34) is shown in Scheme 3.5 [43]. The key reaction in this approach was Trost s asymmetric ally lie alkylation reaction of ethyl 2-fluoroacetoacetate with 34, which afforded 35 in high yield and high enantioselectivity, especially when a bulky tetra-n-hexyl ammonium bromide was used as a phase-transfer reagent (89% yield, 94-96%... 

Trost s group has developed an annulation reagent (a trimethylenemethane syn-thon) which achieves a nucleophilic addition to an aldehyde followed by a ring closure onto a 7r-allyl palladium complex in the one pot (Fig. 15) [18]. 

Fig. 15. Trost s design for the annulation of aldehydes with the trimethylenemethane reagent 57...

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