EXPO2013, the heir of EXPO2009, has been enriched by a variety of new algorithms and graphical tools aiming at strengthening the individual steps of the powder structure solution pathway. Particular attention has been addressed to the procedures devoted to improving structural models provided by direct methods in ab initio approaches. In addition, a new procedure has been implemented, working in direct space, which may be chosen by the user as an alternative to the traditional simulated annealing algorithm.

QUALX2.0 is the new version of QUALX, a computer program for qualitative phase analysis by powder diffraction data. The previous version of QUALX was able to carry out phase identification by querying the PDF‐2 commercial database. The main novelty of QUALX2.0 is the possibility of querying also a freely available database, POW_COD. POW_COD has been built up by starting from the structure information contained in the Crystallography Open Database (COD). The latter is a growing collection of diffraction data, freely downloadable from the web, corresponding to inorganic, metal–organic, organic and mineral structures. QUALX2.0 retains the main capabilities of the previous version: (a) automatically estimating and subtracting the background; (b) locating the experimental diffraction peaks; (c) searching the database for single‐phase pattern(s) best matching to the experimental powder diffraction data; (d) taking into account suitable restraints in the search; (e) performing a semi‐quantitative analysis; (f) enabling the change of default choices and strategies via a user‐friendly graphic interface. The advances of QUALX2.0 with respect to QUALX include (i) a wider variety of types of importable ASCII file containing the experimental diffraction pattern and (ii) new search–match options. The program, written in Fortran and C++, runs on PCs under the Windows operating system. The POW_COD database is exported in SQLite3 format.

A simple, direct one-pot organocatalytic approach to the formation of optically active propargylic fluorides is presented. The approach is based on organocatalytic alpha-fluorination of aldehydes and trapping and homologation of the intermediate providing optically active propargylic fluorides in good yields and enantioselectivities up to 99% ee. The procedure takes place by addition of NFSI, in the presence of 2-[bis(3,5-bis-trifluoromethylphenyl)trimethylsilyloxymethyl]pyrrolidine (as low as 0.25 mol %) as the catalyst, to aldehydes in combination with dimethyl 2-oxopropylphosphonate and 4-acetamidobenzenesulfonyl azide. The scope of the reaction is demonstrated by the formation of a number of optically active propargylic fluorides. It is also shown that optically active fluoro-containing triazoles can be obtained in one-pot procedures from aldehydes using click-chemistry. Furthermore, important coupling and multicomponent reactions of the optically active propargylic fluorides can be performed without affecting the enantiomeric excess. The direct one-pot formation of optically active allylic fluorides from aldehydes is also demonstrated. Finally, the mechanisms for both the formation of the propargylic and allylic fluorides are outlined.

A major driving force for the intriguing developments in the field of total synthesis over the past century is the proficiency with which biological systems transform simple starting materials into complex molecular frameworks. Although necessary issues such as selectivity and synthetic efficiency to construct intricate biological structures can be addressed nowadays to a high degree, new aspects such as diversity and operational efficiency are becoming more important, because of the demand for making complex molecular architectures by effective and simple methodologies.[1] In this respect, catalytic cascade reactions involving two or more selective transformations in one pot are emerging as an attractive tool to overcome the operational limitations associated with traditional "Stop-and-Go" synthesis. [2] Organocatalysis has been shown to be a powerful tool for forming multiple stereocenters in a one-pot protocol by employing either a single catalyst [3a-k] or a combination of catalysts.[3i-l] We became interested in the 4,5-disubstituted isoxazoline-N-oxide motif, since it has the potential to serve as an important building block for diversity orientated total synthesis. Several approaches to isoxazoline-N-oxides are present in the literature either in a racemic fashion, [4] starting from enantiomerically pure compounds, [5] or by employing stoichiometric amounts of a chiral reagent.[6] We envisioned that 4,5-disubstituted isoxazoline-N-oxides having up to three stereocenters could be obtained through a highly stereoselective one-pot procedure using simple and commercially available starting materials in combination with one or two organocatalysts (Scheme 1).Herein, we report a new enantio-and diastereoselective one-pot protocol to access 4,5-disubstituted isoxazoline-Noxides, as well as demonstrate the use of this protocol for the de novo synthesis of b,g-dihydroxylated and b,g,d-trihydroxylated a-amino acid derivatives, phytosphingosines, and amino sugars.Recently, our group reported an efficient and highly enantioselective procedure for the formation of optically active a-bromo aldehydes. [7a,b] Encouraged by the size and leaving group ability of the bromine, we evaluated the possibility of an in situ entrapment, thereby, generating a new class of chiral 1,2-dielectrophiles to participate in multiple-bond-forming cascade sequences. To our delight, the chirality stored within this a-carbonyl sp 3 -carbon center, formed by the direct a-bromination of aldehydes 1 by the electrophilic bromination reagent 2 catalyzed by the TMSprotected diaryl-prolinol 3, is fully exploited by a basepromoted face-selective Henry addition of nitroacetates and subsequent stereospecific O-alkylation, furnishing the enantio-and diastereoselective synthesis of 4,5-disubstituted isoxazoline-N-oxides 4 in one pot (Table 1). The generality of this one-pot, three-step sequence was explored and the results are outlined in Table 1. It appears that b-branched aldehydes 1 a-c provided the 4,5-disubstituted isoxazoline-Noxides 4 a-c as s...

Flow chemistry: A flow-microreactor-mediated synthesis of 1,2,3,4-tetrahydroisoquinolines (THIQs) is reported (see scheme). Starting from a laterally lithiated aziridine, a tetrahydroisoquinoline lithiated at C4 was generated by thermally induced isomerization. Because the reaction temperature is a crucial parameter, the exquisite thermal control possible in a flow-microreactor system allowed for fast, efficient, and highly reproducible synthesis of functionalized aziridines or THIQs.

Innovative methodologies, introduced in the software EXPO and working both in the reciprocal and in the direct space, can be successfully adopted for solving crystal structure by X-ray powder diffraction data. The principles underlying these methodologies are summarized. Three representative examples of crystal structure solution of the peptides Z-(Aib) 2 -OH, Z-(Aib) 3 -O-t-Bu and Z-(Aib) 4 -OH are discussed in relation to their different degree of structure complexity.

a-Lithiated epoxides, long considered "fleeting" intermediates in the reactions of epoxides with strong bases, have nowadays proven to be key synthons for asymmetric synthesis. In this study, the solution and the solid state structure of an a-lithiated aryloxirane, namely a-lithiated ortho-trifluoromethyl styrene oxide (1-Li), were determined. Single crystal X-ray diffraction analysis of 1-Li performed at 100 K applying the X-TEMP-2 device revealed a self-assembled heterochiral dimeric structure with a rare central six-membered (O-Li-C) 2 planar core, which is unprecedented in Li/oxygen carbenoids.Multinuclear magnetic resonance ( 1 H, 13 C, 19 F, 7 Li) studies suggested that 1-Li exists in THF solution as a mixture of two interconverting diastereomeric dimeric aggregates, each one featuring a single s-contact between lithium and a carbon atom. Line shape analysis provided activation parameters for both the dynamic interconversion of the two dimers and the enantiomerisation of 1-Li, which proved to be mostly entropy controlled. The structural assignment in solution was supported by density functional theory computations through the investigation of conformers of monomeric and dimeric complexes of 1-Li featuring different degrees of specific solvation. A mechanism based on the equilibration of sixmembered homo-and heterochiral dimers was proposed to explain the configurational instability exhibited by 1-Li in THF.

The regioselective lithiation-functionalization of 2-arylazetidines has been explored. The nature of the N-substituent is mainly responsible for a regioselectivity switch. ortho-Lithiation occurred, using hexyllithium as a greener base, in N-alkylazetidines, while α-benzylic lithiation has been observed with N-Boc azetidines.