Article pubs.acs.org/jchemeduc
A Simple and Novel Approach To Delineating Stereochemistry of Electrocyclic Reactions Dipak K. Mandal* Department of Chemistry and Biochemistry, Presidency University, Kolkata 700 073, India ABSTRACT: The dynamic stereochemistry of electrocyclic reactions (a class of pericyclic reactions) stems from the operation of either conrotatory (con) or disrotatory (dis) mode of ring-closing and ring-opening processes. Difficulty is often encountered in depicting product stereochemistry resulting from such movements of substituents. A novel, simple, straightforward, and quick approach to delineating product stereochemistry of such reactions is presented. In this approach, the stereochemical properties of reactant and product in electrocyclic reactions are classified as either syn (S) or anti (A). The two substituents at the ends of conjugated polyene system or σ bond of cyclic system in reactant or product are designated as S or A. The product stereochemistry is then delineated as follows: reactant stereochemistry × mode = product stereochemistry, resulting in S × con = S; A × con = A; S × dis = A; and A × dis = S. The procedure is illustrated with several examples of electrocyclic and related pericyclic reactions that are appropriate for an upper-level undergraduate or first-year master’s level organic chemistry course. KEYWORDS: Second-Year Undergraduate, Upper-Division Undergraduate, Organic Chemistry, Mnemonics/Rote Learning, Problem Solving/Decision Making, Reactions, Stereochemistry
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either syn (S) or anti (A). In an electrocyclic ring-closing reaction, a conjugated polyene (reactant) forms a σ bond between the termini of the conjugated π system to form a cyclic compound (product). An electrocyclic ring-opening is the reverse process. The relative stereochemistry of two substituents (X and Y) at the two ends of polyene system is shown in Figure 1A. Two possible syn (S) relationships exist between X and Y and two possible anti (A) relationships exist between them in a conjugated polyene as reactant or product. The relative stereochemistry of X and Y at the two ends of σ bond of cyclic system as syn (S) or anti (A) is shown in Figure 1B. There are also two possible syn (S) and two possible anti (A) relationships for X and Y in cyclic compound as reactant or product. Two possible conrotatory (con) modes and two possible disrotatory (dis) modes are shown in Figures 1C and 1D, respectively. The dynamic stereochemistry of electrocyclic reactions is then readily delineated as
ericyclic reactions are characterized by having single transition states involving cyclic overlap of interacting orbitals and having highly predictable stereochemical outcomes. The reactions obey the selection rules governing whether these are allowed or forbidden. The rules are based on the orbital symmetry control1 or on the aromatic transition-state model.2,3 Among pericyclic classes, electrocyclic reactions and sigmatropic rearrangements are unimolecular, whereas cycloadditions are, in general, bimolecular. The stereochemical idiosyncrasies (thermodynamic or counter-thermodynamic stereochemistry) of the electrocyclic reactions stem from the operation of either conrotatory (con) mode or disrotatory (dis) mode of ringclosing and ring-opening processes. Con and dis modes denote rotation of substituents in the same and opposite directions, respectively, at both termini of the σ bond to be formed or broken. Difficulty is often encountered in depicting product stereochemistry resulting from such movements of substituents. This article addresses the dynamic stereochemistry of electrocyclic reactions and proposes a novel, simple, and straightforward method for delineating stereochemistry of these processes without any reference to orbital mechanisms. A simple approach to assigning relative stereochemistry at a stereogenic center in sigmatropic rearrangements and several other concerted reactions has been presented recently.4 Further, a unifying method for determining absolute configuration at a stereogenic center and a unified con−dis approach to determining stereogenic axis configuration were reported previously.5,6
where the reactant stereochemistry undergoes the specified process to give the product stereochemistry.
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EXAMPLES The examples could be introduced in an organic chemistry course on pericyclic reactions at the upper-level undergraduate or first-year master’s level. The examples were presented in a
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STEREOCHEMICAL PROPERTIES In the present approach, the stereochemical properties of reactant and product in electrocyclic reactions are designated as © 2012 American Chemical Society and Division of Chemical Education, Inc.
Published: May 24, 2012 1041
dx.doi.org/10.1021/ed2002384 | J. Chem. Educ. 2012, 89, 1041−1043
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The method is illustrated with several examples of electrocyclic and related reactions in Figure 2. Consecutive electrocyclic ring-closing and ring-opening steps under thermal condition are shown in Figure 2A. The total number of electrons involved in each step is 4 (4n system, n = 1). Therefore, both steps occur by con mode.1 The product stereochemistry is delineated as any two substituents, say CD3 and Me, which are anti (A), remain anti (A) throughout as A × con = A. Two possible anti stereochemistries for CD3 and Me in the chiral intermediate would imply two enantionmers of the product; however, only one enantionmer is shown in Figure 2A. An example of 6 electron (4n + 2 system, n = 1) electrocyclic ring-opening reaction under photochemical condition is shown in Figure 2B, which occurs by con mode.1 The stereochemistry of the product is drawn as anti (A) relationship between two substituents Me and H and is retained as A × con = A. It may be noted that the other possible anti stereochemistry of Me and H makes both terminal double bonds of the product impossibly trans in 6-membered ring (Figure 2B). As such, a torqueoselectivity (a preference for one of the two possible con modes) operates for the process. Figure 2C shows a thermal 4-electron ring-opening process by con mode followed by 6-electron ring-closing process by dis mode.1 The two H’s (ring junction) that are syn (S) would remain syn (S) in the intermediate as S × con = S. There are two possible syn stereochemistry of H’s of the generated diene moiety that lead to middle double bond of the intermediate triene to be cis
Figure 1. (A) Two possible syn, S, relationships and two possible anti, A, relationships of substituents X and Y at the ends of conjugated polyene system. (B) Two possible syn, S, relationships and two possible anti, A, relationships of X and Y at the ends of σ bond of cyclic system. (C) Two possible conrotatory modes (movements of substituents in the same direction at the termini). (D) Two possible disrotatory modes (movements of substituents in the opposite directions at the termini).
class lecture to serve as a guide for the students to solve the relevant pericyclic problems in their class or take-home assignments and in tests.
Figure 2. Delineation of product stereochemistry in electrocyclic, and related pericyclic reactions: (A) a thermal electrocyclic reaction occurring through ring-closing and ring-opening steps by con mode, (B) a photochemical electrocyclic ring-opening reaction by con mode; (C) a thermal electrocyclic reaction occurring through ring-opening by con mode and ring-closing by dis mode, (D) a linear cheletropic cycloaddition occurring by dis mode, (E) a linear extrusion reaction occurring by con mode, and (F) a Diels−Alder reaction occurring by dis mode with respect to diene. 1042
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ACKNOWLEDGMENTS I would like to thank the anonymous reviewers for helpful suggestions.
or trans (Figure 2C). The intermediate triene with cis geometry of the middle double bond would undergo ring-closing and the terminal H’s of the triene which are syn (S) would become anti (A) at the ring junction of the final product as S × dis = A. Two possible anti stereochemistries of the ring junction H’s would imply two enantiomers of the chiral product, one of which is shown. The triene with trans geometry of the middle double bond would fail to undergo a 6-electron ring-closing reaction (Figure 2C). The method is also applicable to bimolecular cheletropic cycloadditions in which one component is a conjugated polyene. The other is a one-atom two-electron component with no stereochemistry. As such, the stereochemical course of such reactions could be depicted as that for unimolecular electrocyclic process based on the rules of conrotatory− disrotatory motion with respect to the conjugated system. Figure 2D shows a cheletropic reaction as the insertion of SO2 into a stereochemically labeled diene.7 The reaction occurs by a linear cheletropic π4s + ω2s process.2 The suprafacial addition to the diene component (i.e., bond formations on the same face of the diene) necessarily involves disrotatory movement of its terminal substituents. The stereochemistry of the product is depicted as two Me’s which are anti (A) in the diene would become syn (S) in the achiral product as A × dis = S. The linear cheletropic extrusion of SO2 from the seven-membered ring sulfone (Figure 2E) occurs antarafacially with respect to the triene7 and hence leads to conrotatory movement of the methyl substituents. The two syn Me’s would remain syn (S) in the product as S × con = S. The method can also be applied to a Diels−Alder reaction in which both the diene and the dienophile react suprafacially. As the suprafacial diene component of the Diels−Alder reaction belongs to a polyene system, its stereochemical fate could be delineated on the basis of disrotatory movement of its terminal substituents as for electrocyclic process. An example is shown in Figure 2F. The stereochemical fate of the diene component is depicted as two Ph’s which are anti (A) would transform to syn (S) stereochemistry in the cyclic product as A × dis = S. Two possible syn stereochemistries of Ph’s in this case are equivalent for the achiral product.
REFERENCES
(1) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital Symmetry; Verlag Chemie: Weinheim, 1970. (2) Gilchrist, T. L.; Storr, R. C. Organic Reactions and Orbital Symmetry, 2nd ed.; CUP: Cambridge, 1979. (3) Rzepa, H. S. J. Chem. Educ. 2007, 84, 1535−1540. (4) Mandal, D. K. J. Chem. Educ. 2007, 84, 274−276. (5) Mandal, D. K. J. Chem. Educ. 2000, 77, 866−869. (6) Mandal, D. K. Bull. Chem. Soc. Jpn. 2002, 75, 365−366. (7) Fleming, I. Pericyclic Reactions; OUP: Oxford, 1999; pp 7−30.
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SUMMARY It is thus seen that in an electrocyclic reaction, the stereochemical properties of the reactant and product can be classified as either syn (S) or anti (A). The designated property (S or A) remains same in a conrotatory process, whereas it becomes opposite in a disrotatory reaction. The product stereochemistry is delineated without recourse to any orbital mechanism. It seems that the method would serve as a useful supplement to the frontier orbital or other theoretical approaches1−3,7 for discussion of electrocyclic reactions. Finally, the present approach requires minimal or no spatial imagination of same−opposite movements of substituents under con−dis mode. It represents a handy tool or mnemonic, and the delineation of product stereochemistry is not only simple and straightforward, but is probably as fast as one can draw.
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AUTHOR INFORMATION
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[email protected]. 1043
dx.doi.org/10.1021/ed2002384 | J. Chem. Educ. 2012, 89, 1041−1043
