from the C-C bond being formed. The problem of site or ambident reactivity in systems possessing ex tended conjugation is the principal liability in the extension of the construction span. This point is illus trated below for both conjugate addition and enolate alkylation ( Scheme D) Scheme i the problem of ambident reactivity 1.6 Addition Meo a-alkylation 6 MeO2C Nu(-) 1. 4 Addition -==== MeO2C 人入 日(+) r-alkylation The objectives of the present discourse are to present an organizational format which can serve to correlate strategies for the construction simple pairwise functional group relationships. As a result of the overwhelming predisposition of nature to employ polar rather than free radical processes in the biosynthesis of organic compounds the chosen organizational format reflects this bias in reaction type The designation of reactions as polar is recognized to be rather arbitrary since known reactions vary widely in their polar character, ranging from essentially nonpolar radical reactions and weakly polar electrocyclic reactions to strongly polar ionic processes. Of primary concern in this discussion will be those reactions that involve charged species at some point along the reaction coordinate Charge Affinity Patterns. In order to describe an organizational model for the classification and synthesis of heteroatom- heteroatom A-B A B+(4) (difunctional)relationships in organic molecules, two familiar ideas will be employed. The first is that in a given target molecule the A-B B-(5) various bonds can be ionically "disconnected"(eq 4, 5). That is, if the A-B bond could be cleaved heterolytically, the indicated set of polar fragments would result This antithetic process suggests ionic precursors suitable for the construction of the target molecule via polar coupling processes. The second well accepted idea is that functional groups determine site reactivities on a carbon skeleton based upon known reactions. That is, the oxygen atom in both acetone and anisole dictates the site reactivities that are displayed for each molecule with nucleophilic and electrophilic reagents. Thus, if the molecule A-B contained one or he bond one pair of ionic precursors, eg 6 or 7, would be strongly favored A-B as plausible precursors. In such a case the favored ionic(+)( precursors to A-B could be symbolized with either(+)or()in the A-B o target molecule, e.g As an example, two possible polar disconnections for ketone 1 are illustrated below. The parity labels in the target structure suggest plausible monofunctional precursors from which the target structure can be assembled by polar processes. It is also evident that the heteroatom functional groups, =O and-OH, strongly bias the indicated polar disconnections Scheme II Polar Disconnections and Charge Affinity Pattterns T CH2=O CH2-CH2-OH T CHECH H2 5) The use of the symbols, (+)and (-), in no way represents formal positive or negative charges and will always be bracketed to denote this distinction. Other forms of notation have been considered such as(0)and (1)to denote a potential site of electrophilicity or nucleophilicity; however, the chosen symbols convey more direct information to the organic chemist.Functional Group Classification page 2 from the C-C bond being formed. The problem of site or ambident reactivity in systems possessing ex￾tended conjugation is the principal liability in the extension of the construction span. This point is illus￾trated below for both conjugate addition and enolate alkylation (Scheme I). MeO2C MeO2C R R Nu MeO2C R Nu MeO R OM MeO R MeO R O O El El Scheme I The Problem of Ambident Reactivity 4 6 g-alkylation a g Nu(-) El(+) El(+) H + H + a-alkylation 1,4 Addition 1,6 Addition H + H + Nu(-) The objectives of the present discourse are to present an organizational format which can serve to correlate strategies for the construction simple pairwise functional group relationships. As a result of the overwhelming predisposition of nature to employ polar rather than free radical processes in the biosynthesis of organic compounds the chosen organizational format reflects this bias in reaction type. The designation of reactions as polar is recognized to be rather arbitrary since known reactions vary widely in their polar character, ranging from essentially nonpolar radical reactions and weakly polar electrocyclic reactions to strongly polar ionic processes. Of primary concern in this discussion will be those reactions that involve charged species at some point along the reaction coordinate. Charge Affinity Patterns. In order to describe an organizational model for the classification and synthesis of heteroatom-heteroatom (difunctional) relationships in organic molecules, two familiar ideas will be employed. The first is that in a given target molecule the various bonds can be ionically "disconnected" (eq 4, 5). That is, if the A-B bond could be cleaved heterolytically, the indicated set of polar fragments would result. This antithetic process suggests ionic precursors suitable for the construction of the target molecule via polar coupling processes. The second well accepted idea is that functional groups determine site reactivities on a carbon skeleton based upon known reactions. That is, the oxygen atom in both acetone and anisole dictates the site reactivities that are displayed for each molecule with nucleophilic and electrophilic reagents. Thus, if the molecule A-B contained one or more functional groups proximal to the bond to be disconnected, one pair of ionic precursors, eq 6 or 7, would be strongly favored as plausible precursors. In such a case the favored ionic precursors to A-B could be symbolized with either (+) or (-) in the target molecule, e.g.5 As an example, two possible polar disconnections for ketone 1 are illustrated below. The parity labels in the target structure suggest plausible monofunctional precursors from which the target structure can be assembled by polar processes. It is also evident that the heteroatom functional groups, =O and -OH, strongly bias the indicated polar disconnections. R C CH3 O CH2 O R C CH2 O CH2 OH R C CH O CH2 TA TB (+) (–) (+) (–) (–) (–) (+) (–) (+) (–) (–) (+) (–) (+) (–) OH2 1 Scheme II Polar Disconnections and Charge Affinity Pattterns 5) The use of the symbols, (+) and (-), in no way represents formal positive or negative charges and will always be bracketed to denote this distinction. Other forms of notation have been considered such as (0) and (1) to denote a potential site of electrophilicity or nucleophilicity; however, the chosen symbols convey more direct information to the organic chemist. A B A B (5) A: – B+ (4) A: + B:– A B A B A: + B:– A: – B+ (–) (+) (+) (–) (6) (7)