The pyrolysis of 2-ethynyltoluene, indene, fluorene, and related compounds has been studied by sealed tube microwave flash pyrolysis (MFP), in concert with modelling of putative mechanistic pathways by density functional theory (DFT) computations. In the MFP technique, samples are admixed with graphite and subjected to intense microwave power (150–300 W) in a quartz reaction tube under a nitrogen atmosphere. The MFP reaction of 2-ethynyltoluene gave mostly indene, the product of a Roger Brown rearrangement (1,2-H shift to a vinylidene) followed by insertion. An additional product was chrysene, the likely result of hydrogen atom loss from indene followed by dimerisation. The intermediacy of dimeric bi-indene structures was supported by pyrolysis of bi-indene and by computational models. Benzo[a]anthracene and benzo[c]phenanthrene are minor products in these reactions. These are shown to arise from pyrolysis of chrysene under the same MFP conditions. MFP reaction of fluorene gave primarily bi-fluorene, bifluorenylidene, and dibenzochrysene, the latter derived from a known Stone–Wales rearrangement.

Macrocyclic bis-lactams have been synthesized by cyclodimerization of homoallylic amino esters employing a Zr(IV)-catalyzed ester-amide exchange protocol. Base-mediated transannular cyclizations have been identified to access both bicyclic [5][6][7][8][9][10][11] and tricyclic [5-8-5] frameworks in good yield and diastereoselectivity. Preliminary mechanistic studies support an olefin isomerizationintramolecular conjugate addition pathway.Macrocyclic natural products often exhibit important biological activities and have thus inspired a number of studies involving diversity-oriented synthesis of macrocyclic frameworks. 1 Recent studies have also highlighted elegant examples of transannular cyclizations enroute to complex natural products. 2 As part of our studies, we considered preparation of macrocycles as substrates for reaction discovery 3 and potential complexity-generating transannular cyclizations. 4,5 In this communication, we report the preparation of 14-membered ring bislactams 6 and their conversion to polycyclic frameworks by divergent, transannular reaction processes as well as preliminary computational studies to probe the reaction mechanism.In order to access macrocyclic bis-lactam substrates, we utilized cyclodimerization of stereochemically well-defined homoallylic amino esters 7 using Zr(IV)-catalyzed ester-amide exchange. 8 Alloc-protected amino esters 1a-d were prepared using asymmetric crotylation 7 of the iminium species derived from condensation of allyl carbamate with aromatic aldehydes (Scheme 1). Subsequent alloc removal 9 using a polymer-bound Pd (0) reagent (PS-PPh 3 -Pd) 10 simplified product purification and afforded amino ester monomers 2a-d. As cyclodimerization of 2 involves consecutive intermolecular and intramolecular amidations, we anticipated that concentration may play an important role in reaction efficiency. Therefore, a range of concentrations (0.10-0.80 M) were examined for cyclodimerization of 2a using Zr (Ot-Bu) 4 -2-hydroxypyridine (HYP) 8 as catalyst (Scheme 2). Based on these studies, an optimal concentration for production of 14-membered bis-macrolactam 3a was found to be 0.60 M.Macrocyclic bis-lactams 3b-d were also prepared in moderate to good yield using the optimized conditions. The structure and stereochemistry of bis-lactam 3b was confirmed by single x-ray crystal structure analysis (one conformer shown). 10With the target macrolactams in hand, we focused on reaction discovery to identify complexitygenerating transannular cyclizations. Initial attempted intramolecular hydroamidation 11 of bislactam 3b utilizing carbophilic late-transition metal catalysts including Pd(II), Ag(I), Pt(II), Au(I), and Au(III) 12 failed to afford any cyclized products. After reaction screening, use of NaH as base 13 in DMF at 60 °C was found to provide tricyclic [5-8-5] product 5 (dr= 5:1:1) (Scheme 3, entry 1). Reaction at room temperature using NaH gave no conversion indicating a high activation energy for transannular cyclization (Scheme 3, entry 2). Further optimization ...

The reaction of ozone with aldehydes has been studied intermittently for over 100 years, but its mechanism remains uncertain. Experimental results support two reaction channels: radical abstraction of the acyl hydrogen and addition to form a five-membered ring tetroxolane. We have studied the aldehyde-ozone reaction by DFT and CCSD(T) calculations. CCSD(T)/6-311+G(d,p)//M05-2X)/6-311+G(d,p) calculations predict two competitive pathways for the oxidation of formaldehyde by ozone. Abstraction of the acyl hydrogen by ozone has a barrier of 16.2 kcal/mol, leading to a radical pair, which can combine to form a hydrotrioxide; this species may subsequently decompose to a carboxylic acid and singlet oxygen. In the second reaction channel, addition of ozone to the carbonyl is stepwise, with barriers of 19.1 and 23.0 kcal/mol, leading to a five-membered ring tetroxolane intermediate. This process may be reversible, consistent with earlier observations of isotopic exchange. The two channels connect by an intramolecular hydrogen abstraction. Ring opening of the tetroxolane by an alternate O-O bond cleavage, followed by spin inversion in the resulting diradical intermediate, can give a carbonyl oxide plus (3)O(2). It is also possible that reaction of triplet oxygen with carbonyl oxides can produce ozone by the reverse route. These two stepwise reaction channels, hydrogen abstraction and addition to the C=O bond, explain much of what has been observed in the long history of ozone-aldehyde chemistry. Known reaction rates and the substantial barriers to both channels support an earlier conclusion that aldehyde oxidation by ozone is too slow to be of importance in atmospheric chemistry.

The reaction of geminal dihalocyclopropanes with metals or alkyllithiums affords carbenoids which undergo low-temperature ring opening to allenes; this is known as the Doering-Moore-Skattebøl reaction. DFT and CCSD(T)//DFT computations have been used to model the structure, coordination state, and ring opening of 1-bromo-1-lithiocyclopropane as a model for cyclopropylcarbenoid chemistry. Both implicit (PCM) and explicit solvation models have been applied. Carbenoid ring opening is similar to the process predicted in earlier studies on cyclopropylidene. The initial disrotatory stereochemistry becomes conrotatory en route to the allene-LiBr complex. Predissociation of the carbenoid to cyclopropylidene + LiBr is not supported by computations. DFT computations predict modestly exergonic dimerization of the carbenoid, with or without solvation, and the dimer appears to be the most likely reactive species in solution. Predicted barriers to ring opening are only modestly affected by solvation or by dimer formation, remaining in the range of 9-12 kcal/mol throughout.