Cram D J & Elhafez F A A. Studies in stereochemistry. 10. The rule of ‘steric control of asymmetric induction’ in the synthesis of acyclic systems. J. Amer. Chem. Soc. 74:5825-35, 1952

“In 1952 we published ‘The Rule of “Steric Control of Asymmetric Induction” in the Syntheses of Acylic Systems.’ This hypothesis resulted from our syntheses of organic chemical systems needed to investigate our newly discovered ‘phenonium ion.’ Our rule evolved from earlier observations of the Frenchman, M. Tiffeneau, and the Scot, A. McKenzie. These early 20th century investigators observed a pattern in addition reactions where one chiral (handed) carbon center was constructed while attached directly to a second chiral carbon. Two diastereomerically related compounds were produced. These authors found that the predominant isomer depended on the order in which substituents were introduced into the products. “A simple analogy illustrates the evolution of our rule. Imagine that Tiffeneau and McKenzie were assembling diads of N or $$$ letters out of parts, $$$ , turned in any direction. Assume that two three-quarter finished assemblies, N $$ and N $$, were in hand which needed one part to complete the diads. These early authors noticed that addition of one part to one A rule was formulated that correlates and predicts, on the basis of steric effects, the direction of stereochemical bias in addition reactions of aldehydes and ketones in which one chiral carbon is generated in the presence of an attached chiral carbon. [The SCI indicates that this paper was cited 265 times in the period 1961-1976.]