Isothiourea-catalysed chemo- and enantioselective [2,3]-sigmatropic rearrangements of N,N-diallyl allylic ammonium ylides

Abstract

Please cite this article as: West TH, Spoehrle SSM, Smith AD, Isothiourea-catalysed chemo-and enantioselective [2,3]-sigmatropic rearrangements of N,N-diallyl allylic ammonium ylides, Tetrahedron (2017), doi: 10.1016/j.tet.2017.01.062. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Leave this area blank for abstract info. The isothiourea-catalysed chemo-and enantioselective [2,3]-sigmatropic rearrangement of N,Ndiallyl allylic ammonium ylides is explored as a key part of a route to free functionalised α-amino esters and piperidines. The [2,3]-sigmatropic rearrangement proceeds with excellent diastereo-and enantiocontrol (>95:5 dr, up to 97% ee), with the resultant N,N-diallyl α-amino esters undergoing either mono-or bis-N-allyl deprotection. Bis-N-allyl deprotection leads to free α-amino esters, while the mono-deprotection strategy has been utilised in the synthesis of a target functionalised piperidine. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT

Tandem Palladium and Isothiourea Relay Catalysis: Enantioselective Synthesis of α-Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic Rearrangement

“…The high stereoselectivity observed is consistent with competitive racemic [2,3]-rearrangement processes having been completely suppressed without recourse to the addition of additives such as HOBt. 17 , 18 The use of the defined, bench-stable succinimide-based Pd complex 18 (FurCat, 5 mol%), first developed by Fairlamb and co-workers for use in Stille cross-coupling 28 gave further improvement while simplifying the catalytic system, allowing syn - 14 to be isolated in 79% yield as a single diastereoisomer in 99:1 er ( Table 2 , entry 6). Decreasing the catalyst loading of BTM 1 led to reduced yields and stereoselectivity ( Table 2 , entries 7 and 8).…”

“…Notably, the yields and stereoselectivity of this relay Pd/isothiourea catalysis generally exceed those obtained from the previously reported isothiourea-catalyzed [2,3]-rearrangement of isolated allylic ammonium salts. 17 The reactions of non-aryl-substituted allyl phosphate with 13 under the standard relay conditions gave no [2,3]-rearrangement products, with the major product obtained being the corresponding aryl ether formed from allylic substitution with 4-nitrophenoxide. 25…”

“… 16 In 2014, we reported the first catalytic enantioselective [2,3]-rearrangement of allylic quaternary ammonium salts 5 using the isothiourea BTM 1 as a Lewis base and co-catalytic hydroxybenzotriazole (HOBt) to form syn -α-amino acid derivatives 6 with excellent stereoselectivity ( Scheme 2 b). 17 In this process the HOBt additive (i) aids catalyst turnover through interception of a post-[2,3]-rearrangement acylammonium species and (ii) leads to increased diastereo- and enantioselectivity of the [2,3]-rearrangement products. 18 A recognized challenge encountered by ourselves and others 19 for such [2,3]-rearrangement processes is the problematic synthesis and isolation of the required allylic quaternary ammonium salts.…”

Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides

“…This strategy offers a potentially Molecules 2021, 26, 6333 2 of 13 general solution to allow the expansion of electrophile scope within catalytic processes using C(1)-ammonium enolate intermediates. In 2014, we applied this concept for the isothiourea-catalyzed [2,3]-rearrangement of allylic ammonium ylides (Scheme 1b) [60][61][62][63][64]. More recently, this approach has been used by Snaddon (Scheme 1c) [65][66][67][68][69][70][71][72], Hartwig (Scheme 1d) [73] and Gong [74,75] for co-operative isothiourea/transition metal-catalyzed α-functionalization of pentafluorophenyl esters.…”

Multiple roles of aryloxide leaving groups in enantioselective annulations employing α,β-unsaturated acyl ammonium catalysis

“…The use of electron-deficient aryl esters in enantioselective tertiary amine catalysis was first reported by our research group in 2014 for the 2,3-rearrangement of allylic ammonium ylides ( Scheme 1b ). 6 , 7 This method represented a conceptually different approach, with the aryloxide released from the substrate also required to facilitate intermolecular catalyst turnover. 8 This approach, in which the aryloxide performs a dual role, has since been successfully applied in ammonium enolate and α,β-unsaturated acyl ammonium catalysis.…”