Asymmetric Catalytic Oxidative Cleavage of Polycyclic Systems: The Synthesis of Atropisomeric Diazonanes and Diazecanes

Abstract

Oxidative cleavage of internal double bonds in polycyclic systems can give access to compounds containing medium- to large-sized rings. In this example, the nine- and ten-membered ring containing compounds that resulted from the mCPBA-mediated (mCPBA=meta-chloroperoxybenzoic acid) oxidative cleavage reaction were shown to exhibit atropisomerism. The reaction of the polycyclic system with catalytic amounts of ruthenium tetraoxide followed by diol cleavage achieved the same synthetic goal. Use of the Nishiyama-Beller ruthenium-based catalysts enabled the synthesis of optically-enriched samples, providing the first example of an atropselective oxidative cleavage reaction.

N-Tosyl-L-proline benzene hemisolvate: a rare example of a hydrogen-bonded carboxylic acid dimer with symmetrically disordered H atoms

“…Only six structures in the whole data set, viz. ABUNAM (Ermer & Neudö rfl, 2001), IWIHAY (Jones et al, 2011), KIKJOE (Venugopala et al, 2007), REXZUS (Chen et al, 2017), EHUZEN (Leverrier et al, 2010) and RESHIG (Atencio et al, 1997), which is about 0.15%, have a symmetry of the carboxyl dimer similar to that of (I). There were no crystal structures in which a cyclic carboxylic acid dimer has mirror plane symmetry, what proves that twofold axis and inversion centre symmetries are clearly more favourable.…”

Synthesis and Oxidative Cleavage of Oxazinocarbazoles: Atropselective Access to Medium-Sized Rings

“…In contrast to other related systems we have studied, 8 this system enables a much clearer picture of the mechanism of the conversion of 10 into 11 and/or 12 to be deduced. The formation of 11a-e can be rationalised by initial epoxidation of 10a-e, leading to the formation of iminium ion 13.…”

“…Structures of the pyrazino-and oxazino-carbazole systems 1 and 2, respectively, and the polycyclic system 3, which was the focus of our recent asymmetric oxidative cleavage studies 8 Use of the Corey-Bakshi-Shibata (CBS) catalyst enabled asymmetric reduction of 8c to 9c in high yield and 98% ee as judged by chiral HPLC analysis (Scheme 1 and Figure S1). 13 Subsequent cyclisation of 9c using potassium tert-butoxide gave highly optically enriched (R)-2c.…”

“…7 This work extends our previous studies on the oxidative cleavage of compounds of general structure 3, providing additional information on the mechanism of this type of reaction. 8 Commercially available cyclic ketones 4 (n = 1-3, Scheme 1) were treated with ethyl formate under basic conditions to afford α-functionalised ketones 5 (n = 1-3). Japp-Klingemann modified Fisher indole synthesis 9 using a range of anilines gave carbazol-1-ones 6b-j 10a,11 via the corresponding hydrazones 7b-j 10 in reasonable yields, with the exception of 6f 12 (see Table 1 for substituent and ring size).…”

An expedient synthesis of oxazepino and oxazocino quinazolines

“…15,16 Medium-ring containing molecules are challenging to synthesise due to competing effects arising from loss of entropy, Pitzer, Baeyer and transannular strain. 17,18 In particular there is a paucity of information regarding the synthesis of oxazepino [5,6,7-de]quinazolines, and to date, the only four examples have been reported by Bradbury and co-workers 19,20 using Thorpe-Ingold and pseudo-Thorpe-Ingold cyclisation assistance to prepare quinazolines with a 7-membered amide ring junction ( Figure 2). Encouragingly, these examples showed potent inhibition of both EGFR (epidermal growth factor receptor) and erbB2 tyrosine kinase protein phosphorylation.…”