Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Calcium(II)- and Triflimide-Catalyzed Intramolecular Hydroacyloxylation of Unactivated Alkenes in Hexafluoroisopropanol Chenxiao Qi,† Shengwen Yang,†,‡ Vincent Gandon,*,†,‡ and David Lebœuf*,†
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†
Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), CNRS UMR 8182, Université Paris-Sud, Université Paris-Saclay, Bâtiment 420, Orsay 91405 Cedex, France ‡ Laboratoire de Chimie Moléculaire (LCM), CNRS UMR 9168, Ecole Polytechnique, Institut Polytechnique de Paris, route de Saclay, Palaiseau 91128 Cedex, France S Supporting Information *
ABSTRACT: We report an efficient intramolecular hydroacyloxylation of unactivated alkenes, offering a streamlined access to relevant γ-lactones, which features the utilization of either a calcium(II) salt or triflimide as a catalyst in hexafluoroisopropanol. This method could be applied to the synthesis of natural products and the late-stage functionalization of natural and bioactive molecules. Additionally, DFT computations were used to elucidate the twist of reactivity observed between the hydroamidation and hydroacyloxylation of unactivated alkenes regarding the formation of 5- and 6-membered rings.
I
to expand the reactivity of unactivated alkenes, this reaction piqued our attention. In previous studies, we have demonstrated that the association of a catalytic amount of calcium(II) salts5 with hexafluoroisopropanol (HFIP)6,7 was a powerful synthetic tool regarding the hydroamidation of unactivated alkenes8 and the hydroarylation of highly deactivated styrenes.9 In these reactions, the role of calcium is not to act as a traditional Lewis acid that will activate either the nucleophile or the olefin but, instead, to strengthen the acidity of H-bond clusters of HFIP and trigger the hydrofunctionalization process.10 Moreover, what makes this strategy enticing is the remarkable hydrogendonor ability of HFIP, which prevents an unwanted coordination between the substrate and the catalyst by substituting itself to the catalyst. As a result, it usually enables an extended reaction scope with respect to prior reports.8,9 In this context, we believed that our approach could open a new door to rapidly forge γlactones while being compatible with a large variety of precursors. In addition, by means of DFT computations, we tried to shed some light on the difference of selectivity observed between hydroacyloxylation and hydroamidation processes, a common trend often overlooked in the hydrofunctionalization of alkenes. As a first step, we conducted the hydroacyloxylation of 4pentenoic acid 1a (Table 1) using our standard conditions, Ca(NTf2)2/nBu4NPF6 (5 mol %) in HFIP (0.2 M) at 80 °C, which proved to be highly effective in the hydroamidation of unactivated alkenes.8 These conditions led to γ-valerolactone 2a in 92% yield within 2 h (entry 1). Other common solvents were
ntramolecular hydroacyloxylation of unactivated alkenes represents in theory one of the most efficient and atomeconomical processes to provide γ-lactones, notably γbutyrolactones. Taking into account the wide range of applications exhibited by these motifs, whether as agrochemicals, drugs, fragrances, or food additives,1 tremendous endeavors have been dedicated to the development of new and effective protocols for the synthesis of these derivatives,2 bearing in mind that they have to be compatible with a large array of functional groups to be truly meaningful. Yet, to date, most of the methods reported, which feature transition metals or Lewis or Brønsted acids as catalysts, suffer from a lack of versatility and flexibility in terms of reactivity (Scheme 1).3 In addition, in comparison with the hydroamination and hydroalkoxylation of unactivated alkenes,4 only a few catalytic systems have been described. Although the reason behind remains unclear, one could argue that an unwanted coordination between the catalyst and the carboxylic acid might come into play, which makes this reaction still highly challenging. As part of our continuing efforts Scheme 1. Hydroacyloxylation of Unactivated Alkenes
Received: August 2, 2019
© XXXX American Chemical Society
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DOI: 10.1021/acs.orglett.9b02705 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Reaction Optimization for the Formation of γButyrolactone 2aa
entry
catalyst
additive
solvent
time (h)
conversion 2a (%) (yield, %)
1 2 3 4 5 6 7 8 9
Ca(NTf2)2 Ca(NTf2)2 Ca(NTf2)2 Ca(NTf2)2 HNTf2 Ca(NTf2)2
nBu4NPF6 nBu4NPF6 nBu4NPF6 nBu4NPF6
HFIP 1,2-DCE toluene MeNO2 HFIP HFIP HFIP HFIP HFIP HFIP
2 5 5 5 1 2 2 2 2 6
100 (92) 40 (33) NR (−) 100 (79) 100 (63)
