Counting steps

Abstract

The use of step count as a metric of synthetic efficiency carries opportunities and challenges. Here, proposals are made to standardize what constitutes a synthetic step and how steps are counted. These proposals may be beneficial in the holistic evaluation of published synthetic routes.

Fig. 1 |. Defining and reporting synthetic steps.

a, A comparison of enol/enolate bond constructions for aldol adduct 5. b, A single-step three-component, one-pot coupling in the synthesis of X-206. The single step involves: i) 8 (1.00 equiv), ^tBuLi (1.93 equiv.), Et₂O, −78 °C; ii) 9 (0.86 equiv.), −78 °C to 0 °C; iii) LDA (1.5 equiv.), 0 °C; iv) 11 (0.67 equiv.), 0 °C. c, What can we do as synthetic chemists? A common understanding of what constitutes a synthetic step combined with standardized reporting of select metrics can enhance the value of these data to readers of the chemical literature. ⁱPr, iso-propyl; LDA, lithium diisopropylamide; MOP, methoxyisopropyl mixed ketal; ^tBu, tert-butyl; Tf, trifluoromethanesulfonyl; TMS, trimethylsilyl.