Fundamentals 2

• D/L devised by Disher and Rosanoff • Based on Fischer projections • The +enantiomer of glyceraldehyde was selected by Rosanoff as an arbitrary reference compound • The + enantiomer was designated D as the OH group attached to C2 is on the right side

• Longest carbon chain is vertical and the ligand with the highest oxidation level is placed at the top • All the vertical bonds point down into the page and all the horizontal bonds point upwards • The interchange of any two ligands at a stereogenic centre changes the configuration of that centre

• With D-(+)-glyceraldehyde as a reference compound other enantiopure compounds could be related to it by a series of reactions or degradations • Compounds that could be correlated either directly or indirectly to the reference compound using chemical reactions that don’t lead to racemisation at the chiral centre were labelled D • All amino acids- L • Almost all carbs- D

• No link

• It only allows the specification of the absolute configuration of a single stereocenter in a molecule - not always clear which stereocenter should be described • It is restricted to molecules that can be unambiguously drawn as Fischer projections and which obey all relevant rules • All organic compounds increase in complexity, it becomes more and more impractical to chemically correlate them to glyceraldehyde • Some organic compounds are well correlated to either glyceraldehyde - leads to different names

• Enantiomeric excess (ee) • Tells you what percentage of the mixture is not a racemate

• Racemic = 0% • 1 enantiomer = 100%

• eeR=R-S/R+S *100 • eeS=S-R/S+R *100

• The optical purity of a compound as measured by polarimetry can be equated with %ee, provided that these two quantities are linearly related • Historical use of polarimetry is why %ee is defined how it is • The phrase optically pure for enantiopure compounds is strongly discouraged because polarimetry is no longer used to measure %ee and not all enantiopure compounds exhibit measurable optical activity

• Enantiomeric ratio (er) • Ratio of one to the other

• er=R/S or er= S/R • Typically written as ratio xx:yy normalised to 100 e.g. 97:3 • 3 in 100 have S config- 6% racemic • 94% = ee%

• Used instead to report relative amounts of diastereomers • It is again usually normalised to 100

• Tetrahedral stereocentres at silicon, phosphorus, sulfur and nitrogen • Heteroelements from Group IV-VI with tetrahedral are also stereogenic if the 4 ligands are all different • Chiral@Si compounds are known and have even been prepared in enantiopure form • But this is more commonly encountered for oxides of organic phosphorus or sulfur compounds in their P(V) or S(VI) oxidation states, and is also known for N-oxides or ammonium salts of amines

• If 3 ligands are different • Nitrogen, sulfur and phosphorus

• They are usually subject to rapid pyramidal inversion (invertomers) and are macroscopically achiral on a time average • If there is another stereocenter within the molecule such that the nitrogen invertomers are diastereomeric, the amine will generally adopt the most thermodynamically stable configuration - least strained • In suitably constrained amines, the lone pair inversion can become impossible on account of structural rigidity

• Increasing the s-character of the N lone pair by: • Increasing the electronegativity of the ligand(s) • Or ring strain • Chiral oxaziridines

• Inversion is extremely slow for heavier atoms like P and S • Therefore simple phosphines and sulfoxides are configurationally-stable and their enantiomers can be resolved

• A molecule that is permanently twisted bears an axis that can become stereogenic with appropriate substitution- stereogenic axis • If this leads to chirality it is termed axial chirality as opposed to central chirality for stereogenic centres

• Allenes • Rotationally restricted biaryls

• Three double bonded carbons connected • Central carbon is SP-hybridised • The remaining two p orbitals on the central carbon overlap with the p orbitals on the terminal carbons to produce two pi bonds. • These pi bonds are perpendicular so the molecule is twisted. • Requires unsymmetrical substitution at both ends

• The restricted rotation • E.g BINOL, where steric crowding prevents co-planarity of the two napthyl rings and they are unable to slip past each other

• When restricted rotation is the cause of stereoisomerism

• Another way of generating chirality • A planar unit in a molecule which is constrained in such a way as to place atoms/groups permanently out of plane • Just as for centres of axes, non-symmetrical substitution is required on the plane to render it stereogenic • Chirality arising this way is sometimes called planar chirality

• Organometallic sandwich complexes • Form basis of many chiral enantiopure organocrystals and ligands