A protecting group free and biomimetic total synthesis of (+)-ainsliadimer A has been accomplished in 14 steps from α-santonin. The synthesis relies on a hydrogen bonding promoted [4 + 2]-hetero-Diels-Alder dimerization to afford the key homodimer intermediate, which demonstrates the feasibility of using nonenzymatic conditions to achieve the proposed biosynthesis.

A diastereoselective 6π-electrocyclic ring-closure employing halogen-substituted 3-amidotrienes via a 1,6-remote asymmetric induction is described. This new asymmetric manifold for pericyclic ring-closure further underscores the significance of the allenamide chemistry.Identifying a highly stereoselective manifold for 6π-electron electrocyclic ring-closure of 1,3,5-hexatrienes remains a challenge in the field of pericyclic processes. 1, 2 We recently reported that a 1,3-H shift of allenamides 1 3,4 provides an excellent entry to amidotrienes 2, which could undergo 6π-electron pericyclic ring-closure. 5,6 The ring-closure could be rendered in tandem with the 1,3-shift, 5,6 leading to the facile construction of rare chiral cyclic amidodienes 3 [Scheme 1]. 7,8 While we were able to demonstrate the possibility of attaining a stereoselective ring-closure using 2, the level of selectivity was very modest. However, these efforts unveiled an invaluable opportunity not only to develop a new and attractive template for conducting stereoselective 6π-electrocyclic ring-closures, but also to achieve a highly challenging 1,6-asymmetric induction. 9 Consequently, we examined isomerizations of 1 via electrophilic halogenations, leading to 2-halo-amido-trienes 5 through N-acyl iminium ions 4.We recognized two distinct advantages of this electrophilic isomerization over the thermal one:3b , 5 , 10 ,11 (i) installing a halogen substituent at the C2-position of amidotrienes 5 allows for strategic functionalizations at C1 of 6 that is originally the central allenic β-carbon; and (ii) more importantly, the halogen atom can serve as a key chirality relaying element in the ring-closure to achieve the desired 1,6-asymmetric induction. We envisioned that a disrotatory ring-closure through amidotrienes 7 in the upward direction could be significantly favored with enhanced steric interaction between the R 1 group on the chiral amide and R 3 [H versus X] on the triene. We disclose here our success in developing a stereoselective 6π-elecytron pericyclic ring-closure of halogen-substituted amidotrienes via a 1,6-remote asymmetric induction.Our efforts commenced with electrophilic brominations of the α-benzyl -substituted allenami de 8 12,13 as summarized in Table 1. Initial attempts involved reacting 2 equiv of * rhsung@wisc.edu . Supporting Information Available:Experimental procedures as well as NMR spectra, charact erizations, and X-ray structural files are available for all new compounds and free of charge via Internet http://pubs.acs.org. . We attribute this loss in the yield to hydrolysis of the starting allenamide due to the byproduct HBr, and that evidently the excess amount of allenamide used in earlier attempts was simply being sacrificed to soak up HBr. Consequently, we screened a number of bases and found that addition of 2 equiv of DABCO [entry 6] to be the most optimal in effectively promoting this bromination reaction without sacrificing excess of allenamide. NIH Public AccessHaving established the optimized conditions ...

In this study, a concise and atom-economical TfOH-mediated [2 + 2 + 2] cycloaddition of ynamides with two discrete nitriles is developed to synthesize multi-substituted 4-aminopyrimidine.

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