Five-Membered-Ring Formation

In the construction of carbocycles, five-membered ring formation has been used for preparing fused cyclic compounds, such as functionalized diquinanes. ° The reaction of 36 with (TMSlsSiH furnished the expected product 37 in 80% yield and in a or.fi ratio of 82 18, as the result of a kinetic controlled reaction (Reaction 43). 

As with five-membered ring formation, the reactions of ADC compounds which lead to six-membered ring heterocycles can be classified according to how the ADC compound reacts in the initial step. Most common is the Diels-Alder reaction, with the ADC compound acting as dienophile. Six-membered rings also result from the reaction of monoenes with ADC compounds acting as the 4n component, and by cyclization or other transformation of an initial adduct. 

The dimerization reaction has been applied to intramolecular cyclization of bis(diene)s, leading to the formation of five- and six-membered ring products bearing two allylic silane moieties (Equation (42)).125 Although stereoselectivity depends on the substrate structure, trans-(E,Z) isomers are generally favored in the five-membered ring formations. 

Scheme 16.9 Mechanism of a five-membered ring formation.

Each of the above cyclizations proceeds upon a 6-exo-trig mode process promoting the formation of six-membered rings as opposed to the more common five-membered ring formation. 

Photochemical abstraction/ recombination can be used to effect direct five-membered ring formation. This reaction can be highly diastereoselective, as shown by the photocyclization of 2-(2-ethylphenyl)-1 -phenylethanone1 The diastereoselectivity of radical recombination is influenced by the reaction medium a 20 1 ratio in benzene becomes a 2 1 ratio in methanol. 

Steve Martin of UT Austin has reported (J. Org. Chem. 68 8867,2003) a detailed study of the synthesis of bridged azabicyclic structures via ring-closing alkene metathesis. Some examples of his work include the conversion of 12 to 13, efficiently forming six, seven and eight membered rings. He also demonstrated five-membered ring formation with the conversion of 14 to IS, which has the cocaine skeleton. 

Intramolecular five-membered ring formation occurs in the alkaline-catalyzed hydrolysis of a series of esters of 2-hydroxypropylphosphate, where a linear free-energy relationship is found for the rate of alkoxide expulsion as a function of the pKa of the alcohol. No evidence for phosphoryl migration was obtained consistent with the fact that pseudorotation of the presumed intermediate leading to ring opening would be inhibited (50), viz. 

Regiocontrol in intramolecular cyclopropanation is mainly dependent on the site of the unsaturated centre related to the carbenoid centre. In other words, ring size of the bicyclic or polycyclic systems which derive from the cyclopropanation is the key to regiocontrol of this type of reaction. The regioselectivity is independent of the catalyst employed, Five-membered ring formation is favoured over the production of six- or seven-membered rings... 

In situ generation of an allylstannane from an allylic acetate and hexamethyldistannane results in five-membered ring formation in preference to the allyl alternative seven-membered ring (equation 243).140... 

Addition to a vinylsilane takes place regioselectively (equation 25)67. A trialkylsilyl group can be used in this way to direct ring formation so as to form a six-membered ring (equation 26) in opposition to the usual preference for five-membered ring formation in... 

Acid-catalyzed iV,0-acetal reaction of iV-BOC protected 2-amino-1,4-butanediol 208 with dimethoxypropane gave only moderate yields of 209 because of concurrent six- and five-membered ring formation (Scheme 59) <20050L1423>. 

Nitrogen Nucleophile Attacking sp2 or sp3 Carbon Five-Membered Ring Formation... 

I) Five-membered ring formation, (2) Six-membered ring formation, (3) Seven- and eight-membered ring formation, and finally (4) Tandem cyclization. 

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