Transannular C-H insertion

Transannular C—H Insertions in Epoxides of Medium-sized Cydoalkenes... 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

To extend the scope of asymmetric transannular C-H insertions, more highly functionalized medium-sized cyclic epoxides have been investigated. A triad of cydooctene oxides 34, 36, and 38, possessing protected diol units, gave the expected alcohols 35, 37, and 39 (Scheme 5.10) [17, 18] an asymmetric synthesis of (-)-xialenon A has been achieved starting from alcohol 39 [19]. In comparison,... 

Whereas exo-norbornene oxide rearranges to nortricyclanol on treatment with strong base through transannular C-H insertion (Scheme 5.11), endo-norbornene oxide 64 gives norcamphor 65 as the major product (Scheme 5.14) [15, 22]. This product arises from 1,2-hydrogen migration very little transannular rearrangement is observed. These two reaction pathways are often found to be in competition with one another, and subtle differences in substrate structure, and even in the base employed, can have a profound influence on product distribution. 

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

Upon photolysis of azicyclooctane (40), cw-cyclooctene (44) is readily formed, but so too are products derived from intramolecular C-H insertions of carbene 41. Of special interest is bicyclo[3.3.0]octane (42). Created from a 1,5-CH insertion within carbene 41 (Scheme 8),124 r/.v-fused 42 needs space to form. Since the free volume (A V) of a CyD depends on the number of monomer units of which it is comprised, it is not surprising that these factors conspire to limit bicyclo[3.3.0]octane (42) formation when azicyclooctane (40) is photolyzed within ot-CyD (Table 4).42,125 The occurrence of transannular C-H insertion becomes less probable as the cavity within the molecular reaction vessel gets smaller. 

The most recent developments in the above area mainly concern enantioselective variants of these reactions (vide infra). The asymmetric version of transannular C-H insertions from enantioenriched hthiated epoxides has been extensively studied in the Hodgson laboratory over the last six years. In these... 

Note added in proof. ktotA synthesis of (-)-xialenon A using bicyclic alcohol 77 [Eq. (26)] represents the first application of enantioselective a-hthiation transannular C-H insertion of epoxides in natural product synthesis [78]. The first enantioselective generation - intermo-lecular nucleophile trapping of a lithium carbenoid has been described, via enantioselective a-deprotonation of the epoxides of oxa- and aza-bicyclic alkenes [e.g. 93 Eq. (30)] using alkyl-lithiums in the presence of (-)-sparteine or bisoxazoline 5 [Eq. (3)] [79]. Insertion of a second... 

Ring closure with tosylhydrazones 3,7-Transannular C—H-insertion... 

Thianoradamantane has been synthesized in moderate yield starting from cyclo-octa-2,7-dienone. The important reaction in the sequence (Scheme 31) is the transannular C—H insertion by a carbenic species. 

Reaction of exo-9-oxabicyclo[4.2.1]non-7-ene oxide with n-BuLi to exo-S-hydroxybicyclo[3.3.0]octan-2-one has been suggested to occur by elimination to a transient allene oxide that rearranges to a trans-tpoxide enolate before undergoing epoxide a-lithiation and transannular C-H insertion. " ... 

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