摘要：

Fluorination often confers a range of advantages in modulating the conformation and reactivity of small molecule organocatalysts. By strategically introducing fluorine substituents, as part of a β-fluoroamine motif, in a triazolium pre-catalyst, it was possible to modulate the behaviour of the corresponding N-heterocyclic carbene (NHC) with minimal steric alterations to the catalyst core. In this study, the effect of hydrogen to fluorine substitution was evaluated as part of a molecular editing study. X-ray crystallographic analyses of a number of derivatives are presented and the conformations are discussed. Upon deprotonation, the fluorinated triazolium salts generate catalytically active N-heterocyclic carbenes, which can then participate in the enantioselective Steglich rearrangement of oxazolyl carbonates to C-carboxyazlactones (e.r. up to 87.0:13.0). Introduction Molecular editing using fluorine is a powerful strategy to modulate the conformation and reactivity of small molecule organocatalysts [1-3]. The negligible steric penalty associated with H→F substitution, together with the polarised nature and stability of aliphatic C–F bonds, render this unit attractive from the perspective of molecular design [4]. The low-lying antibonding orbital (σC–F*) can interact with an array of vicinal substituents ranging from non-bonding electron pairs, such as in the case of the fluorine anomeric effect [5], to electron rich sigma bonds (σ→σ*). The stereoelectronic gauche effect in 1,2difluoroethane is the most prominent example (1; Figure 1) [6-9]. The counterintuitive preference of vicinal fluorine substituents to adopt a gauche preference (ΦF–C–C–F ≈ 60°) can be rationalised by invoking two stabilising hyperconjugative interactions (σC–H→σC–F*). This conformational preference is conserved in numerous systems in which one of the fluorine atoms has been substituted by another electron withdrawing group (X(δ+); X–Cα–Cβ–F). Often this modification leads to the introduction of a stabilising electrostatic component, thus enhancing the interaction: this is exemplified by the pioneering work of O'Hagan and co-workers [10-12]. In recent years, this laboratory has strategically employed the aforementioned effects in the design of functional small moleBeilstein J. Org. Chem. 2013, 9, 2812–2820. 2813 Figure 2: Target triazolium salts 5–10 for this study. The synclinal-endo conformation of 5 is shown [18]. Only the synclinal-exo arrangement of 6 and 7 is shown [22]. Figure 1: Exploring the effect of fluorine incorporation in triazolium pre-catalysts (2) for the enantioselective Steglich rearrangement of oxazolyl carbonates to the respective C-carboxyazlactones (3→4). cules [13-22], often for application in organocatalysis [1]. Common to these studies has been the strategic incorporation of a fluoro substituent vicinal to a catalytically active amino group. Subsequent generation of a (partial) positive charge at nitrogen generates the requisite X–Cα–Cβ–F system (X = N+), thus providing a facile approach to controlling rotation around this bond (ΦXCCF ≈ 60°). In this study, the influence of fluorination on catalyst behaviour is extended to the study of triazolium salts such as 2, which can be converted to the respective N-heterocyclic carbenes (NHCs) by simple deprotonation. Given the importance of NHCs in modern organic synthesis [23-28] it was envisaged that these systems would be intriguing candidates for investigation. Moreover, structural information gleaned from the triazolium salt pre-catalysts regarding conformation [18,22], assist in rationalising the behaviour of the NHCs generated in situ. Herein, the synthesis and catalytic efficiency of a series of fluorinated, bicyclic triazolium salts 2 is disclosed. The effect of molecular editing by hydrogen to fluorine substitution is evaluated in the NHC-catalysed, enantioselective Steglich rearrangement of oxazolyl carbonates 3 to C-carboxyazlactones 4 [29], recently reported by Smith and co-workers [30-36]. Fluorination sites were selected based on their proximity to the ring junction

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