The development of robust catalytic methods to assemble tertiary alkylamines provides a continual challenge to chemical synthesis. In this regard, transformation of a traditionally unreactive C-H bond, proximal to the nitrogen-atom, into a versatile chemical entity would be a powerful strategy for introducing functional complexity to tertiary alkylamines. A practical and selective metal-catalyzed C(sp 3)-H activation facilitated by the tertiary alkylamine functionality, however, remains an unsolved problem. Here, we report a Pd(II)-catalyzed protocol that appends arene feedstocks to tertiary alkylamines via C(sp 3)-H functionalization. A simple ligand for Pd(II) orchestrates the C-H activation step in favor of deleterious pathways. The reaction can utilize both simple and complex starting materials to produce a range of multi-faceted g-aryl tertiary alkylamines and can

Stereoselective total syntheses of (-)-histrionicotoxin and (-)-histrionicotoxin 235A are described. The 1-azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation-cyclization reaction involving a chiral cyclic acetal; the use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity. The cyclization product was converted into (-)-histrionicotoxin 235A through a one-pot partial-reduction-allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (-)-histrionicotoxin.

An acylsilane synthesis by a Pd-catalyzed cross-coupling reaction of thiol esters and silylzinc chlorides was developed. S-Phenyl thiol esters with a variety of functional groups were converted to corresponding acylsilanes.Since acylsilanes possess a variety of unique reactivities, 1 their synthesis has been an important research topic in organic chemistry.1p1r,24 Brook 2a and Corey 2b independently reported representative methods to prepare acylsilanes by silylation of a lithiated dithiane followed by removal of dithiane. Acylsilanes are also synthesized by 1,2-addition of silyllithium to aldehydes followed by oxidation according to a procedure of Reich. 5However, both methods have only limited functional group compatibility since they use strong bases such as n-BuLi. To circumvent these problems, palladium-catalyzed cross-coupling of acid chlorides with disilane 4a4d or stannylsilane 4e has recently been reported. These methods, however, are unsatisfactory because they require harsh conditions such as heating at high temperature without solvent. On the other hand, thiol esters are a suitable substrate for cross-coupling reactions based on oxidative addition of a transition-metal catalyst to the CS bond. 6,7 Under this background, we initiated a study of the transformation of thiol esters to acylsilanes. Herein, we report a mild synthesis of acylsilanes by palladium-catalyzed crosscoupling of thiol esters and silylzinc chlorides.Based on the proposed reaction mechanism for the palladium-catalyzed cross-coupling reaction of thiol esters with organozinc reagent (Scheme 1), we considered a working hypothesis for transformation of thiol esters to acylsilanes as shown in Scheme 2. Oxidative addition of palladium(0) to the CS bond of the thiol ester gives acyl palladium species which should be transformed to the acylsilane via transmetalation with a silyl metal reagent followed by reductive elimination with regeneration of Pd(0).With this idea in mind, we explored a suitable silyl metal reagent for the expected cross-coupling reaction. Using thiol ester 1a as the model substrate, various silyl metal reagents 4,8

Total synthesis of (−)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation−cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol. After the radical translocation−cyclization reaction, a hydroxymethyl group at the C-13 position was stereoselectively introduced by a one-pot partial reduction−allylation protocol of the unprotected lactam derivative. Finally, the total synthesis is completed by formation of a C ring.

Stereoselective total syntheses of (À)-histrionicotoxina nd (À)-histrionicotoxin 235A are described. The 1azaspiro[5.5]undecane skeleton was constructed diastereoselectively by aradical translocation-cyclization reaction involving ac hiral cyclic acetal;t he use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity.T he cyclization product was converted into (À)-histrionicotoxin 235A through ao ne-pot partial-reduction-allylation reaction of ad erivative containing an unprotected lactam. Finally,t wo terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (À)-histrionicotoxin.