Computer‐Assisted Planning of Organic Syntheses: The Second Generation of Programs

Abstract The planning of syntheses in organic chemistry has continuously been given more solid foundations during the last decades. Widely applicable rules have been formulated. Nearly parallel with the systematization of this field the potential for the automation of synthesis planning by the use of computers has been promulgated. However, after more than two decades of continuing efforts by a number of groups, computer‐assisted synthesis planning, which relies on large libraries of synthons and transforms, has failed to establish itself firmly. This is in marked contrast to the acceptance of reaction databases. Their use has become routine with a surprisingly short time. Apparently the classical approaches to computer‐assisted synthesis planning do not satisfy the needs of the preparative chemist. However, this lack of success does not yet mean the complete demise of the whole field. The conceptual shortcomings and problems of the first generation of programs are both of technical and psychological nature and need to be critically analyzed. Meanwhile, work has begun on systems of the second generation, which try to support the chemist in the synthesis laboratory with new methods in novel ways. Care is taken to mimic and support the typical planning style of the human chemist, who often on the spur of the moment switches direction in planning as well as his (sub) goals and methods. New tools that correspond better to the thinking patterns and working habits of chemists empower the user to plan syntheses of organic molecules in an interactive and innovative fashion. We feel that this field is far from dead and continue our research activities. In this article we introduce a system with a number of novel concepts and demonstrate its capabilities with some practical examples.