Transannular alkylation

Chang et al. reported a mild tandem intramolecular hydroamination of yne amines to form an endo-adduct intermediate, which reacts with electron-deficient azides to produce cyclic amidines <06JA12366>. Selected examples of an interesting synthetic route to tropene derivatives 165 via a dual hydroamination strategy is shown below. This one-step reaction makes use of a palladium catalyst and takes place by sequential intermolecular hydroamination of cycloheptatriene with aryl, heteroaryl, and primary alkyl amines to generate intermediate 166, followed by transannular intramolecular hydroamination <06JA8134>. 

Michael-type addition of a suitable nucleophile, e.g. thiols, on to the a,f)-unsaturated lactone. Such alkylation reactions are believed to explain biological activity, and, indeed, activity is typically lost if either the double bond or the carbonyl group is chemically reduced. In some structures, additional electrophilic centres offer further scope for alkylation reactions. In parthenolide (Figure 5.31), an electrophilic epoxide group is also present, allowing transannular cyclization and generation of a... 

Bicyclic 3a//-cyclopentene[8 annulcnc-l,4-(5//,9a//)-dioncs undergo three types of acid-induced transannular reactions (1) Michael addition (5-exo-trig or 6-exo-trig) leading to the tetracyclic diones, (2) 3 + 2-cycloaddition followed by a novel sequential skeletal rearrangement to 2-naphthalenone derivatives, (3) ipso-Friedel-Crafts alkylation accompanied by the rearomatization and the loss of water (Scheme 25). The factors that control the reaction mode of these transannular cyclizations are discussed... 

Ishii and coworkers developed a Mn(OAc)2-catalyzed hydrophosphonation of alkenes 40 (Fig. 47) [271]. The active Mn(III) catalyst is generated by reaction of Mn(OAc)2 with oxygen. Hydrogen abstraction from diethyl phosphite 169 forms a phosphonyl radical, which adds to 40. The resulting alkyl radical is reduced by 169 to continue the chain reaction. Alkylphosphonates 170 were isolated in 51-84% yield. With (3-pinene a cyclobutylcarbinyl radical ring opening was observed in 32% yield, while 1,5-cyclooctadiene underwent a tandem radical addition/ transannular 5-exo cyclization (cf. Fig. 38). 

Campbell, J.A. et al. Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3+3]-Coupling and Transannular Alkylation. 2.4 1995(111]... 

Transannular reactions of enamines with the amino group of one side of a medium-size ring and the C=C double bond on the other side of the ring, positioned so that it can interact with the amine nitrogen, have been observed316. For example, protonation of 201 gives the transannular bonded product 202, but alkylation leads to the open product 203 (equation 23). 

H. Yuasa, J. Tamura, and H. Hashimoto, Synthesis of per-O-alkylated 5-thio-D-glucono-l,5-lactones and transannular participation of the ring sulphur atom of 5-thio-D-glucose derivatives on solvolysis under acidic conditions,./. Chem. Soc. Perkin Trans., 1 (1990) 2763-2769. 

Ammonolysis of alkyl acetoacetates with 15% aqueous ammonia at 25 °C initially led to the formation of alkyl /3-aminocrotonates 372a,b, which slowly converted into the iminodiazocine 53, as the main product. A plausible mechanism is depicted in Scheme 73. Once formed, the aminocrotonates underwent further ammonolysis to give /1-arni nocroton amide, which cyclodimerized to give the diazocinedione 373, which, in the presence of ammonia, finally underwent a transannular Michael addition to give 53 <2002T55>. 

Bicyclo[ 1.1.1 ]pent-l-yl anion 16. The basicity and electrophilicity of 16 relative to ordinary tertiary alkyl anions are not easy to predict without a computation. On the one hand, the high percent of s character in the hybrid holding the lone pair on the bridgehead carbon atom suggests that this anion will have quite low basicity. On the other hand, the transannular interaction between the two bridgehead carbons can be expected to increase the basicity, due to a relief in transannular closed-shell repulsions when a lone pair is replaced by a bond at the bridgehead. Indeed, the computed (MP2/6-31G ) interbridgehead distance decreases from 1.974 A in the anion to 1.872 A in bicyclo[l.l.l] pentane ... 

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