Asymmetric Synthesis of trans-3,4-Dialkyl-γ-butyrolactones via an Acyl-Claisen and Iodolactonization Route

Abstract

[reaction: see text] A new, efficient, and general asymmetric synthesis of enantiomerically pure trans-3,4-dialkyl-gamma-lactones has been developed. The key steps are (1) copper-catalyzed three-component coupling of chiral amine, aldehyde, and alkyne, (2) acyl-Claisen rearrangement, and (3) iodolactonization. The products, chiral gamma-lactones, are versatile synthetic intermediates and structural units of natural products and modified nucleosides.

A Concise Total Synthesis of (+)‐Tetrabenazine and (+)‐α‐Dihydrotetrabenazine

“…To the best of our knowledge, use of a Grignard reagent such as iPrMgCl is the first example for ACR. [20][21][22][23] With the key ten-membered lactam 3 to hand, we explored an electrophile-assisted transannulation strategy [14,25] for the construction of the desired benzoisoquinolizidine scaffold of (+)-2 (Scheme 4). Fortunately, the transannulation of lactam 3 to afford the benzoisoquinolizidine 9 could be accomplished with the assistance of TsOH (RT, benzene, 24 h) with the concomitant cleavage of the TBS ether in a highly diastereoselective fashion (36:1, 84 % yield, isolated).…”

Copper‐catalyzed one‐pot synthesis of propargylamines via CH activation in PEG

“…The model reaction of benzaldehyde (1a), morpholine (2a) and phenylacetylene (3a) was conducted to screen the optimal reaction conditions and the results are listed in Table 1 [8][9][10][11][12].…”

Carbohydrate Chemistry for RNA Interference: Synthesis and Properties of RNA Analogues Modified in Sugar-Phosphate Backbone

“…18 may be difficult to modify for preparation of all four doubly modified nucleosides that are required for synthesis of uniformly modified amide-linked RNA (A M 2 ) . Therefore, we explored a total synthesis [120,121] of 3'-azidomethyl-5'-carboxylic acids 64 (Fig. 19) following the same principles as for the 5'-azido-3'-carboxymethyl derivatives 51 (Fig.…”

“…Because our attempts to use the ene reaction as a starting point were not successful, we chose a stereoselective [3,3]-sigmatropic rearrangement as a route to the key iodolactonization precursor 60. After considerable experimentation with Ireland-Claisen and aza-Claisen rearrangements [120,121], the most efficient synthetic entry was achieved when using the zwitterionic Belluš-Claisen rearrangement [122]. Thus, a copper bromide mediated asymmetric three component coupling [123] followed by a Lindlar reduction gave the allyl amine 59 [121].…”

“…After considerable experimentation with Ireland-Claisen and aza-Claisen rearrangements [120,121], the most efficient synthetic entry was achieved when using the zwitterionic Belluš-Claisen rearrangement [122]. Thus, a copper bromide mediated asymmetric three component coupling [123] followed by a Lindlar reduction gave the allyl amine 59 [121]. Treatment of 5 9 with benzyloxyacetyl chloride under conditions developed by MacMillan and co-workers [124] (triethylamine and TiCl 4 ) initiated a zwitterionic [3,3]sigmatropic rearrangement that gave the amide 60 in good yield and stereoselectivity.…”