Aliphatic and aromatic 1,4-bifunctional compounds bearing a primary alcoholic function and an amine can be efficiently cyclised with dimethyl carbonates in the presence of a base to achieve 5-membered N-heterocyclic compounds. This novel synthetic pathway is quantitative, one-pot and green as it does not involve the use of chlorine solvents or reagent.N-Based heterocycles are very abundant in nature since they are present as structural subunits in many natural products such as vitamins, hormones and alkaloids. 1 These compounds are also interesting from an industrial point of view especially for the synthesis of pharmaceuticals, herbicides, pesticides, dyes, etc. 1 Among the reaction pathways leading to nitrogen-containing heterocycles, many involve heavy metals, e.g. metal-catalyzed intramolecular cyclisation of aliphatic a,w-diamine, 2 intramolecular and intermolecular Ru-catalyzed reactions, 3 intramolecular cyclisation of diallyl amine by Grubb's catalyst, 4 or gas-phase high-temperature reaction using zeolites. 5 In recent years, more sustainable approaches for the synthesis of N-based heterocycles have been reported, 6 such as photocatalytic cyclisation of a,w-diamine carboxylic acids by aqueous semiconductor suspensions 7 and microwave-assisted synthesis from alkyl dihalides and primary amines. 8 However, most of the above-mentioned reactions still require high temperature and long reaction time, utilize chlorine-based chemistry or eventually organic chlorinated solvents.Short chain dialkyl carbonates such as dimethyl carbonate (DMC), produced nowadays by clean processes, 10 are renowned for possessing properties of low toxicity and high biodegradability, which make them true green solvents and reagents. 11 DMC has been used as efficient eco-sustainable substitute of the most common methylating and carboxymethylating agents such as phosgene, methyl halides or methylsulfate that are toxic and highly corrosive. 12 Dialkyl carbonates and in particular DMC have shown high selectivity with different monodentate and bidentate nucleophiles acting as methylating and/or carboxymethylating agent. 13 The reactivity of the two electrophilic centers of DMC can be selectively tuned, temperature being the key factor. In fact, usually at reflux temperature (T = 90 • C) DMC acts as methoxycarbonylation agent by B Ac 2 mechanism while at higher temperature (T > 150 • C) the methylation reaction occurs via the B Al 2 mechanism. Both reactions produce as by-product only methanol and eventually CO 2 . 11-13 Exploiting the DMC (B Al 2-B Ac 2) chemistry, recently we reported a novel, one-pot, environmentally benign and chlorinefree synthetic pathways for the synthesis of 5-membered cyclic ethers by intramolecular cyclisation of 1,4-diols. 9

The large molecules 1-3 (69, 90, and 102 atoms, respectively), prepared by cyclotrimerization of enantiomerically pure derivatives of (2)-bornyl acetate, show intense ECD spectra, high optical rotation (OR) values (200-1300, in absolute value) dominated in sign and order of magnitude by the lowest-energy Cotton effects, that is, they are the ideal candidates to test the reliability of our ''approximate'' (TDDFT/B3LYP/6-31G* or smaller basis set) approach to the calculation of chiroptical properties. As a matter of fact, a correct simulation of the OR values and ECD spectra of 1 and 2 can be obtained even using STO-3G basis set and semiempirical or molecular mechanics input geometries: for 1, at the TDDFT/B3LYP/STO-3G level, the OR values are of the order of 500-550, versus an experimental value ranging between 660 and 690, depending on the solvent. On the contrary, the case of 3 (exp. OR between 21330 and 21500) is really complex (for instance, the OR values range between 23216 and 2729 (TDDFT/B3LYP/6-31G* calculations) or 21824 and 2444 (TDDFT/B3LYP/STO-3G calculations)), making the comparison between calculated and experimental values more difficult. The behavior of 3 is due to its molecular flexibility, whereas 1 is a really rigid molecules and 2 behaves (vide infra) as it were a rigid system. These observations strongly indicate that the conformational freedom constitutes one of the major difficulties for a correct but simple simulation of the chiroptical properties.

A dimethyl carbonate‐promoted intramolecular cyclization of aliphatic and aromatic 1,4‐amino alcohols (I), (V), and (VII) is achieved in the presence of a base to afford the corresponding 5‐membered aza‐cyclic molecules.