Cyclizations transannular electrophilic

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... 

Electrophilic transannular cyclization of nine-membered ring lactam 129 led to formation of protected methyl 6-amino-8-iodo-5-oxooctahydroindolizine-3-carboxylates 130a and 130b in high yields (Equation 4) <20060L2851>. 

This chapter summarizes those transannular reactions in medium ring carbocycles which result in carbon-carbon bond formation via alkylation of carbon, in the presence of electrophilic reagents. It is therefore a logical extension of two other chapters in this volume, covering Friedel-Crafts Alkylations (Chapter 1.8), and Polyene Cyclizations (Chapter 1.9). The discussion of these processes is organized according to the size of the cycloalkene from which transannular cyclization is effected. 

Transannular cyclization in cycloocta-l,S-diene (16 equations 6 and 7) can be brought about a wide variety of electrophilic reagents. These reactions lead to a range of functionalized bicy-clo[3.3.0]octanes (Tables 1 and 2), many of which have found widespread use in general synthesis. Although the use of mineral acids favors Ae formation of bicyclo[3.3.0]octanes, other electrophilic agents... 

Transannular cyclization of the (Z,Z)-isomer (51) of cyclonona-1,5-diene in the presence of a variety of electrophilic reagents provides a useful synthesis of a range of substituted ci.r-hydrindane derivatives (53 Table 4). In each of these cases the 1,5-diene unit in (51) is reacting in the T-conformation shown in (52). 

The transannular cyclizations described in Sections 1.10.1-1.10.6 are unique to medium-sized ring systems. Although transannular electrophilic processes are known with smaller rings, i.e. 3- to 7-rings, many of these processes can best be reviewed in terms of nonclassical carbonium ion phenomena. Some selected examples are collected in equations (73-77). 

Sesquiterpenes with eleven carbon atoms in the ring, for example humulene, have been subjected to electrophilic reactions providing products of transannular cyclization. 

The tandem cyclization-cycloaddition reaction of 1-diazoacetyl-7,7-dimethylbicyclo[2.2.1]heptan-2-one (1) with dimethyl butynedioate catalyzed by rhodium(II) acetate dimer in benzene at 25 °C, afforded a formal [3 + 2] cycloadduct 2 in 85% yield with complete diastereofacial selectivity48. This reaction is interpreted to proceed via rhodium carbenoids and subsequent transannular cyclization of the electrophilic carbon onto the adjacent oxo group to generate a cyclic carbonyl ylide. followed by 1,3-dipolar cycloaddition. Similar reactions are observed with other dipolar-ophiles, such as propargylic esters and A -phenylmaleimide. Studies dealing with the geometric requirements of dipole formation were undertaken. 

Electrophile-induced transannular cyclizations of DBAs were also reported for [10]annulene systems (Scheme 7.9). Reaction of iodine with [10](2.2)dinaph-thoannulene 26c gave diiodozethrene 38a, which was transformed to diethynylze-threne derivatives such as 38b by Sonogashira coupling reaction [120-122]. Moreover, bromine-induced double cyclization of highly strained [10](4.2)DBA 39 afforded dibenzopicene 40a [123]. 

Natural products containing six-membered rings are ubiquitous, therefore the following set of target molecules are limited to those containing eight-membered rings that would be accessible via [4+4] cycloadditions. Notably, 1,5-cyclo-octadienes 88 can be converted to bicyclo[3.3.0]octanes 201 transannular electrophilic [124] and radical cyclization (Sch. 44) [125]. 

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