Exo-bonded substituents

Exo-Bonded Substituents and Other Main Group Derivatives of the 9 Ions. 80... 

Recently, the stereochemical definitions of the addition of carbenes to C-C double bonds have been summarized. The term stereoselectivity refers to the degree of selectivity for the formation of cyclopropane products having endo vs. exo or, alternatively, syn vs. anti orientation of the substituents in the carbene species relative to substituents in the alkene substrate. The term stereospecificity refers to the stereochemistry of vicinal cyclopropane substituents originating as double-bond substituents in the starting alkene, i.e. a cyclopropane-forming reaction is stereospecific if the cisjtrans relationship of the double-bond substituents is retained in the cyclopropane product. Diastereofacial selectivity refers to the face of the alkene to which addition occurs relative to other substituents in the alkene substrate. Finally, enantioselectivity refers to the formation of a specific enantiomer of the cyclopropane product. 

Another line of evidence that bridging is important in the transition state for solvolysis has to do with substituent effects for groups placed at C-4, C-5, C-6, and C-7 on the norbomyl system. The solvolysis rate is most strongly affected by C-6 substituents, and the exo isomer is more sensitive to these substituents than is the endo isomer. This implies that the transition state for solvolysis is especially sensitive to C-6 substituents, as would be ejqiected if the C(l)—C(6) bond participates in solvolysis. ... 

Another stereochemical feature of the Diels-Alder reaction is addressed by the Alder rule. The empirical observation is that if two isomeric adducts are possible, the one that has an unsaturated substituent(s) on the alkene oriented toward the newly formed cyclohexene double bond is the preferred product. The two alternative transition states are referred to as the endo and exo transition states ... 

There are probably several factors which contribute to determining the endo exo ratio in any specific case. These include steric effects, dipole-dipole interactions, and London dispersion forces. MO interpretations emphasize secondary orbital interactions between the It orbitals on the dienophile substituent(s) and the developing 7t bond between C-2 and C-3 of the diene. There are quite a few exceptions to the Alder rule, and in most cases the preference for the endo isomer is relatively modest. For example, whereas cyclopentadiene reacts with methyl acrylate in decalin solution to give mainly the endo adduct (75%), the ratio is solvent-sensitive and ranges up to 90% endo in methanol. When a methyl substituent is added to the dienophile (methyl methacrylate), the exo product predominates. ... 

When this stereoelectronic requirement is combined with a calculation of the steric and angle strain imposed on the transition state, as determined by MM-type calculations, preferences for the exo versus endo modes of cyclization are predicted to be as summarized in Table 12.3. The observed results show the expected qualitative trend. The observed preferences for ring formation are 5 > 6, 6 > 7, and 8 > 7, in agreement with the calculated preferences. The relationship only holds for terminal double bonds. An additional alkyl substituent at either end of the double bond reduces the relative reactivity as a result of a steric effect. 

Tertiary pyrrolines (49, = 1) and piperideines (49, = 2) (if R = H and the enamine can exist in the monomeric form or if R = aryl) evidently possess an endocyclic -double bond (79,155,156). The stretching frequency of the double bond can be lowered to 1620-1635 cm by conjugation with an aromatic substituent. The double bond of an analogous compound with aliphatic substituents in position 2 may occupy either the endo or the exo position. Lukes and co-workers (157) have shown that the majority of the five-membered-ring compounds, traditionally formulated with the double bond in a position, possess the structure of 2-alkylidene derivatives (50) with an exocyclic double bond, infrared absorption at 1627 cm . Only the 1,2-dimethyl derivative (51) is actually a J -pyrroline, absorbing at 1632 cm . For comparison, l,3,3-trimethyl-2-methylene pyrrolidine (52) with an unambiguous exocyclic double bond has been prepared (54). 

The Diels-Alder reaction of a diene with a substituted olefinic dienophile, e.g. 2, 4, 8, or 12, can go through two geometrically different transition states. With a diene that bears a substituent as a stereochemical marker (any substituent other than hydrogen deuterium will suffice ) at C-1 (e.g. 11a) or substituents at C-1 and C-4 (e.g. 5, 6, 7), the two different transition states lead to diastereomeric products, which differ in the relative configuration at the stereogenic centers connected by the newly formed cr-bonds. The respective transition state as well as the resulting product is termed with the prefix endo or exo. For example, when cyclopentadiene 5 is treated with acrylic acid 15, the cw fo-product 16 and the exo-product 17 can be formed. Formation of the cw fo-product 16 is kinetically favored by secondary orbital interactions (endo rule or Alder rule) Under kinetically controlled conditions it is the major product, and the thermodynamically more stable cxo-product 17 is formed in minor amounts only. 

Cyclization of an organolithium tethered to a suitably positioned carbon-carbon jt-bond is a thermodynamically favorable process that proceeds in a totally regioselective exo-fashion with a high degree of stereocontrol via a transition state in which the lithium atom is intramolecularly coordinated with the remote rc-bond.9 The stereochemical outcome of the cyclization of a substituted 5-hexenyllithium follows from the preference of the substituent to occupy a pseudoequatorial position in the chair-like transition state depicted below.7... 

When free radicals are added to 1,5- or 1,6-dienes, the initially formed radical (9) can add intramolecularly to the other bond, leading to a cyclic product (10). When the radical is generated from an precursor that gives vinyl radical 11, however, cyclization leads to 12, which is in equilibrium with cyclopropylcarbinyl radical 13 via a 5-exo-trig reaction. A 6-endo-trig reaction leads to 14, but unless there are perturbing substituent effects, however, cyclopropanation should be the major process. 

Intramolecular enone-alkene cycloadditions are also possible. In the case of (3-(5-pentenyl) substituents, there is a general preference for exo-type cyclization to form a five-membered ring.195 This is consistent with the general pattern for radical cyclizations and implies initial bonding at the (3-carbon of the enone. 

Entry 10 shows the occurrence of 5-exo cyclization. The radical in this case is generated from an amino sulfide. This reaction requires a specific, somewhat disfavored conformation of the reactant in order for cyclization to occur. When the unsubstituted vinyl substituent was used, no cyclization occurred. However, increasing the reactivity of the double bond by adding the ester substituent led to successful cyclization. 

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