Quaternary centres bearing a nitrogen substituent (α-tertiary amines and their derivatives) are found in a variety of bioactive molecules but pose a major challenge in synthesis, particularly when enantiomeric purity is required. Approaches comparable to those used for tertiary alcohols are typically hampered by the poor electrophilicity of imines, requiring powerful nucleophiles that may also act as bases. A set of powerful alternative approaches make use of the rearrangement of readily available precursors, often (but not always) with formation of a new tertiary carbon to nitrogen bond. In this Feature Article we review the scope, limitations and specificities of some of these rearrangements in order to illuminate their synthetic potential.

Enantiomerically pure tertiary thiols provide a major synthetic challenge, and despite the importance of chiral sulfur-containing compounds in biological and medicinal chemistry, surprisingly few effective methods are suitable for the asymmetric synthesis of tertiary thiols. This review details the most practical of the methods available.

Synthetic twists among lipids: Proteins embedded in cell membranes perform a wide variety of signaling and transport functions through conformational shifts. De Poli et al. examined how a much smaller, simpler construct might begin to achieve similar aims (see the Perspective by Thiele and Ulrich). Specifically, they designed an artificial peptide with a photosensitive group at one end and embedded it in a phospholipid bilayer akin to a membrane. Nuclear magnetic resonance spectroscopy revealed how light-induced isomerization influenced conformational dynamics at the other end. The results point the way toward development of small-molecule–based switches in membrane environments. Science , this issue p. 575 ; see also p. 520