Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 3 10 helical conformations in which enantiomeric left-and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a righthanded screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.

An N-terminal L-α-methylvaline dimer induces complete conformational control over the screw sense of an otherwise achiral helical peptide foldamer formed from the achiral quaternary amino acids Aib and Ac6 c. The persistent right-handed screw-sense preference of the helix enables remote reactive sites to fall under the influence of the terminal chiral residues, and permits diastereoselective reactions such as alkene hydrogenation or iminium ion addition to take place with 1,16-, 1,31-, 1,46- and even 1,61-asymmetric induction. Stereochemical information may be communicated in this way over distances of up to 4 nm.

(1)H NMR studies quantify the abilities of achiral amino acids to communicate a left-handed screw-sense preference from one helical Aib(4) domain to another: certain quaternary amino acids (e.g. Ac(6)c) act as effective conductors of conformational preference while others (e.g. diphenylglycine) acts as insulators.

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A study of the organocatalytic activity of N-heterocyclic carbenes (NHCs) in the Michael addition of 1,3-dicarbonyl compounds has allowed us to identify 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) as an excellent catalyst for this transformation (up to 99 % yield with a 2.5 mol % catalyst loading), and the reaction was found to be of broad scope. Two early applications of this unprecedented catalytic activity of NHCs are described, that is, the domino carbocyclization reactions of simple cyclic 1,3-dicarbonyl and malonic acid derivatives, which allow stereoselective access to bridged bicyclic compounds, and the stereoselective synthesis of cyclohexanols (or cyclohexene). Early mechanistic investigations are also reported.

An N-terminal l-a-methylvaline dimer induces complete conformational control over the screw sense of an otherwise achiral helical peptide foldamer formed from the achiral quaternary amino acids Aib and Ac 6 c. The persistent right-handed screw-sense preference of the helix enables remote reactive sites to fall under the influence of the terminal chiral residues, and permits diastereoselective reactions such as alkene hydrogenation or iminium ion addition to take place with 1,16-, 1,31-, 1,46-and even 1,61-asymmetric induction. Stereochemical information may be communicated in this way over distances of up to 4 nm.In a typical stereoselective reaction, existing stereochemistry governs the formation of a new stereogenic center by controlling the direction of attack of a reagent or a catalyst at a reactive site. Close spatial contact between the controlling center and the reaction site is typically required, and 1,2or 1,3-asymmetric induction (where the two sites are separated by one or two bonds) can routinely be expected to give high levels of stereoselectivity. [1] Asymmetric induction over longer distances ("remote asymmetric induction" usually refers to 1,4-asymmetric induction and beyond) is possible, [2] but only if the flexibility of the molecule is limited, usually by the (sometimes temporary) formation of a cyclic structure. [3] Asymmetric induction can be achieved over more than 20 bonds [4] in non-cyclic molecules by using semi-rigid structures in which relayed interactions between a series of polarized groups allow a controlling stereogenic center to influence the local environment of a remote reactive site. [5] Here we present a way to achieve asymmetric induction over much greater distances by using molecules that have inherent helicity, or foldamers. [6,7] The conformational properties of foldamers as structural analogues of biomolecules have been investigated widely, [7][8][9] but their ability to control reactivity remains largely unexplored. [10] By linking an appropriate controller and a reactive site through a molecular fragment strongly disposed to adopt a helical structure, we show that it becomes possible for the controlling center to govern the stereochemical environment at a remote reactive site located several nanometers away.The helical foldameric parts of our molecules were made from oligomers of aminoisobutyric acid (Aib, 1) and 1aminocyclohexanecarboxylic acid (Ac 6 c, 2) (Figure 1 a). Peptide-like oligomers of these achiral quaternary amino acids typically adopt well-defined 3 10 helical structures in solution, [11] but because the individual amino acids each possess a plane of symmetry, their oligomers exist as a rapidly interconverting [12,13] equal mixture of left-and right-handed helices. A bias towards a single screw sense [14] was induced by ligating to the N-terminus of these oligomers one or more residues of the chiral quaternary amino acid l-a-methylvaline (aMv, 3). The structure of l-a-methylvaline is compatible with the 3 10 helical structure of Aib oligomers, [15] ...

An efficient synthesis of cis-2-amino-1-fluorocyclobutane-1-carboxylic acid in single enantiomer form was established and protected homo-oligomers (2-, 4-, and 6-mers) of this cyclic cis-b-amino acid were prepared. Conformational analysis of these oligomers using IR, NMR and CD techniques in solution, supported by molecular modelling studies, suggested a strong conformational preference for a welldefined strand-like structure in which intra-residue hydrogen bonding is weak at best and is not consequential for adoption of the secondary structure. Single crystal X-ray analysis of the tetramer showed that a regular strand-like conformation is adopted in the solid state; only intermolecular hydrogen bonding networks are observed. The backbone topology and the 4-membered ring orientations are noticeably different from those of the tetramer of the corresponding non-fluorinated cis-b-amino acid.

A general strategy for the synthesis of arylthio cyclopropyl carbaldehydes and ketones via acid catalysed arylthiol addition/ring contraction reaction sequence has been exploited. The procedure led to a wide panel of cyclopropyl carbonyl compounds in high yields and broad substrate scope.