Transannular cyclization cycloaddition reactions

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. 

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... 

Several detailed investigations of transannular IMDA cycloadditions have appeared in recent years. This transformation promises to become an important synthetic method owing to the potential for the rapid efficient construction of complex polycyclic ring systems. Other potenti strategic benefits include increased reactivity due to diminished entropic requirements (AS ). This is nicely illustrated by the facile cyclization of (101) with a tetrasubstituted dienophile, compared with the unsuccessful IMDA reaction of (102) (Figure 27). Although the cyclization of (101) proceeds with only moderate diastereoselection, many other examples have been reported that exhibit outstanding selectivity, e.g. cyclization of (103). It is conceivable that conformational constraints imposed by the macrocyclic system may lead to improved IMDA stereoselectivity relative to conventional acyclic trienes, but this point has not yet been demonstrated in any published examples. 

The intramolecular Diels-Alder cyclization of cyclohexadiene-l,2-dicarboxylic anhydride-derived diester-tethered triene (86) produces the cycloadducts in a ratio of 7 1 (Scheme 31). The intramolecular Diels-Alder reactions of amino acid-derived trienes (87) yield cycloaddition products (88) and (89) which are mainly cw-fused and derived from the exo-transition states (Scheme 32). A key reaction in the synthesis of the natural product momilactone A is the transannular Diels-Alder cyclization of the trans-trans-cis alkene (90) to the trans-syn-trans tricycle (91) (Scheme 33). The Diels-Alder cycloaddition of 1 l-oxapentacyclo[6,5,2,2 0 0 ]-heptadeca-4,14,16-triene-4,5-dicarboxylic anhydride (92) with cyclopentadiene proceeds with 5yn-facial selectivity to produce syn,endo and syn,exo cycloadducts (93) and (94)... 

Debenzoyltashironin, a densely functionalized polycyclic natural product that induces neurite outgrowth in fetal rat cortical neurons, was synthesized by Danishefsky and co-workers using a biomimetic synthetic route. As shown in Scheme 20.4, the cyclic quinone monoketal 10 was formed by oxidative dearomatization of 9 followed by intramolecular O-cyclization. The transannular Diels-Alder cycloaddition was observed during this process. However, a 4-minute microwave irradiation was needed to complete the reaction to give 11 in 65% yield. It is remarkable that such a complex polycyclic ring system was assembled in two steps. Incorporation of a trisubstituted allene as the dieno-phile of 9 was important because the transannular Diels-Alder reaction did not proceed when an alkene dienophile... 

---