A series of 11 simple phylloquinone derivatives, each lacking the extended phytyl side chain but featuring H-bond donor amides at one or both peri positions, were prepared and some salient physical properties were measured. A correlation between both IR frequency and NMR peak position, as indicators of internal H-bond strength, and the quinone half-wave reduction potential, was observed. These data are consistent with the prevailing hypothesis that quinone carbonyl H-bonding in general, and stronger H-bonds in particular, favorably bias the endogenous quinone's electrochemical potential toward easier reduction.The complete structural characterization of the photosynthetic reaction centers Photosystem 1 (PS1) 1 and bacterial reaction center (bRC) 2 has enabled unparalleled advances in understanding the mechanistic underpinnings of photosynthesis. 3 Even as Angstrom-level features have come into focus, the relationship between structure and function, in many cases, has yet to be clarified. One pivotal feature of the light-driven electron transfer from each system's primary chlorophyll acceptor to the terminal repository, a quinone (bRC) or Fe 4 S 4 cluster (PS1), involves reaction through an intermediate quinone transfer junction (ubiquinone (1) in bRC and phylloquinone (2) in PS1), Fig. 1. The critical reduction potentials of these quinones are thought to be responsive to local electrostatic effects, with proximal negatively charged amino acid side chains and a juxtaposed negatively charged iron-sulfur cluster contributing to a lower value (harder to reduce) for phylloquinone in PS1 compared with an adjacent and reduction-facilitating Fe 2+ site in bRC. 4 In addition to these charge effects, both H-bonding and π-stacking also are cited as influential factors in determining the quinone reduction potential. Ubiquinone is pinioned by the protein matrix between two H-bonds as shown, and so it is not surprising that it's estimated reduction potential in vivo is higher than (more easily reduced than) the same quinone in the non-protic media DMF. Whereas the inexact modeling of a protein interior by DMF does not allow too firm of a conclusion to be drawn, it is likely that at least some of the diminished reduction potential of the in vivo version can be attributed to dual H-bond activation of the quinone's carbonyls. It is quite surprising, then, that the analogous quinone 2 of PS1 exhibits a reduction potential that is substantially lower than various phylloquinone models in DMF solution, given that it, too, presumably benefits from the single H-bond shown. 5 The role that the enveloping protein plays in modulating the reduction potential of this quinone has been a matter of speculation, and one theory in current Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is publishe...

Thermolysis of 2-(allenyl)phenylazides leads to a cascade cyclization sequence furnishing both C (2)-C(3) and N-C(2) cyclopentennelated indoles.Organic synthesis via diyl cyclization has had an episodic history, with surges in activity quickly following discovery of novel diradical generating reactions. 1 One of the more notable advances to emerge from this area of chemistry stemmed from the observation that N 2 extrusion from 4-methylene-1,2-diazenes led efficiently to triplet trimethylenemethane (TMM) diyls, species that have served a central role in numerous cyclization-and cycloaddition-based approaches to cyclopentanoid natural products. 2 One little studied modification of the TMM diyl, azatrimethylenemethane (ATMM), can be constructed, at least in principle, by simply exchanging one methylene fragment for a nitrogen (cf. 4 , Scheme 1). By analogy with TMM chemistry, the ATMM variant might provide ready access to polycyclic cyclopentanoid alkaloid frameworks. The development of ATMM chemistry has laged far behind its all-carbon cousin, but early studies that hinted at its existence 3 and more recent suggestions of its intermediacy in azide-allene cyclization cascades 4 (Scheme 1) may yet elevate this species to a position of prominence in lkaloid synthesis. C(2)-C(3) annelated indoles represent one potential target class for this chemistry, and given the success of the 1→5 conversion, wherein only cyclization through the imine species 4b was observed, it seemed plausible to expect that incorporation of an aryl residue in the allene-azide tether (cf. 6) would lead by analogy to the C(2)-C(3) cyclopentennelated indole products 7. As described in this report, this goal was achieved in practice. However, the unanticipated intervention of subtle electronic (?) effects, presumably as a consequence of the electronic connectivity supplied by the intervening aryl ring, served to divert some of the reactive intermediate(s) down alternative channels, leading to N-C(2) annelated products as well. A description of the scope of this process for cyclopentennelated indole synthesis with both alkenyl-and aryl-substituted 2-(allenyl)phenylazides is detailed below.The syntheses of suitable 2-(allenyl)phenylazides of the type 6 were accomplished by straightforward chemistry using Konno's procedure for palladium-mediated aryl(alkenyl)zinc ksf@chem.psu.edu. addition to propargylic acetates 9, 5 or the cuprate-based alternative procedure of Palenzuela, 6 Table 1. The azide function survived exposure to these organometallic reagents with no detectable decomposition, but attempts to add (Bu 3 Sn)CuSPh to 9a met with concomitant azide reduction to furnish an amide product following O-to-N acetyl transfer. The (alkenyl)allenyl azides 6a-6i were stable, isolable, and characterizable compounds, but the aryl-substituted analogues 6j-6m were sensitive to chromatography and could not be isolated in pure form. Therefore, these species were routinely carried on to the thermolysis procedure as crude materials. NIH Public AccessThe t...

A density functional theory based computational approach to describing the mechanistic course of the allene azide cycloaddition cascade sequence has been developed. The results of these calculations permit characterization of key reactive intermediates (diradicals and/or indolidenes), and explain the different behaviour observed in the experimental studies between conjugated and non-conjugated species. Furthermore, computational analysis of certain intermediates offer insight into issues of regioselectivity and stereoselectivity in cases where different reaction channels are in competition, suggesting suitable substitutions to achieve a single regioisomer in the indole synthesis via azideallene cyclization.