Formation of Five-Membered Rings Intramolecular

The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

Formation of Five-Membered Rings Intramolecular 8-H Abstraction... 

Formation of five-membered rings. Intramolecular insertion of Rh carbenoids into... 

The most useful of the insertion processes is the intramolecular reactions that occur with high selectivity for the formation of five-membered ring products. The electrophilic nature of the process is suggested by C-H bond reactivity in competitive experiments (3°>20 >1°) [76, 77]. Asymmetric catalysis with Rh2(MPPIM)4 has been used to prepare a wide variety of lignans that include (-)-enterolactone (3) [8], as well as (R)-(-)-baclofen (2) [7],2-deoxyxylolactone (31) [80,81],and (S)-(+)-imperanane (32) [82].Enantioselectivities are 91-96%... 

The aldol reaction can be applied to dicarbonyl compounds in which the two groups are favorably disposed for intramolecular reaction. Kinetic studies on cyclization of 5-oxohexanal, 2,5-hexanedione, and 2,6-heptanedione indicate that formation of five-membered rings is thermodynamically somewhat more favorable than formation of six-membered rings, but that the latter is several thousand times faster.170 A catalytic amount of acid or base is frequently satisfactory for formation of five- and six-membered rings, but with more complex structures, the techniques required for directed aldol condensations are used. 

Scheme 2.10 illustrates intramolecular aldol condensations. Entries 1 and 2 are cases of formation of five-membered rings, with aldehyde groups serving as the electrophilic center. The regioselectivity in Entry 1 is due to the potential for dehydration of only one of the cyclic aldol adducts. 

Intramolecular insertion reactions show a strong preference for formation of five-membered rings.219 This was seen in a series of a-diazomethyl ketones of increasing chain length. With only one exception, all of the products were five-membered lactones.220 In the case of n = 3, the cyclization occurs in the side chain, again forming a five-membered ring. 

Vinyllithium cyclizations. The vinyl lithiums formed from trisylhydrazones (9, 486) can participate in intramolecular cyclizations. This anionic cyclization is presently limited to formation of five-membered rings. It has the advantage of greater stereoselectivity than a corresponding radical cyclization. 

Vacuum thermolysis (160°C) of the hemiaminal 11 generates the azaphos-phetane 65 in 85% yield.32 This product clearly results from the intramolecular insertion of the transient (amino) (phosphino)carbene 2h into the C-H bond of a diisopropylamino group bonded to phosphorus. Note that the four-membered heterocycle 65 is formed exclusively in spite of the ratio of six methyl-CH bonds to one methine-CH bond, and that only one of the two possible diastereomers is detected. The same regio- and diastereo-selectivity have already been observed with the di(phosphino)carbene 2g,74 but is in marked contrast to the exclusive formation of five-membered rings... 

Intramolecular carbene C-H insertion frequently leads to the formation of five-membered rings [967,990,1021,1113-1128], In particular l-diazo-2-alkanones tend to yield cyclopentanones exclusively when treated with rhodium(ll) carboxylates. The use of enantiomerically pure catalysts for diazodecomposition enables the preparation of non-racemic cyclopentane derivatives [1005,1052,1074,1092,1129]. Intramolecular 1,5-C-H insertion can efficiently compete with 1,2-C-H insertion... 

Iodine is a very good electrophile for effecting intramolecular nucleophilic addition to alkenes, as exemplified by the iodolactonization reaction.49 Reaction of iodine with carboxylic acids having carbon-carbon double bonds placed to permit intramolecular reaction results in formation of iodolactones.50 The reaction shows a preference for formation of five-membered rings over six-membered ones51 and is a strictly anti stereospecific addition when carried out under basic conditions. 

Type I cyclizations are generally restricted to the formation of five-membered rings, whereas formation of six-membered rings occurred more readily than that of five- or seven-membered rings in type II cyclizations. Examples of intramolecular zinc-ene reactions of both types have been reported. 

It is also possible to achieve the formation of five-membered rings by coupling the allylzincation of a metallated alkyne with an intramolecular nucleophilic substitution. Thus, allylzincation of the ethylzinc alkynylide generated from 5-iodo-l-pentyne (66)45, or direct treatment of the latter with excess crotylzinc chloride177, led to the alkenyl... 

The transition metal catalyzed synthesis of five membered heterocycles, particularly of condensed ring systems, has attracted considerable attention. The ease of the formation of five membered rings has been utilised both in intramolecular ring closure processes, and in the combination of two (three) fragments through the formation of a carbon-carbon and a carbon-heteroatom bond. This chapter is dedicated to examples, where the construction of the five membered heterocycle is achieved in a transition metal catalysed step. 

Intramolecular oxysulfenylation.1 Intramolecular oxysulfenylation (11, 205) of y,8-unsaturated alcohols or acids can be used for preparation of cyclic ethers or lactones, respectively. A base is not essential, but optimal yields are obtained in the presence of diisopropylethylamine (1.1 equiv.). Formation of five-membered rings is favored over formation of six-membered rings. The reaction is carried out at 25° and requires 1-3 days. 

The intramolecular addition of organolithiums to non-activated carbon-carbon double or triple bonds has now become an efficient way of constructing carbocyclic and heterocyclic systems. Although mainly confined to the formation of five-membered rings, the high regio- and stereoselectivity of these reactions and the possible functionalization of the... 

The yields depend on the size of the ring formed, decreasing in the order 3>5>6 >4 i7. Formation of five-membered rings is inhibited in the presence of a proton donor (dimethyl malonate) and cyclization to four-, six- and seven-membered rings is completely prevented. However, these conditions have little effect on the formation of the three-membered rings [221]. The authors interpret the results of their preparative studies as a competition between protonation and intramolecular Sn2 reaction on the radical anion stage. However, it seems more likely that the competition is between protonation and cyclization of the /S-carbanion formed en route to hydrogenation. 

Chiral Ci-symmetric lanthanocenes (see Fig. 4) have achieved enantioselectivities of up to 74% (36) in various intramolecular hydroamination reactions [27,146,147]. While complexes 1-3 are better suitable for the formation of five-membered rings. 

The course of intramolecular enone alkene photocycloaddition is dependent on the number of atoms between the two reactive C=C bonds. For example, E- and Z-isomers of 1-acylhepta-1,6-diene (147) form a 1 1 mixture of stereoisomeric cycloadducts 148 and 149 upon irradiation, while no E Z isomerization occurs (Scheme 6.67a).764 The initial bonding takes place between the C2 (Cp) and C6 atoms, in agreement with the empirical rule of five,165 the regioselective, kinetically preferred formation of five-membered ring biradical intermediates over larger rings due to the entropies of cyclization. As a result, the biradical 150 is not observed. For comparison, the acylhexadiene 151 photolysis also proceeds via a 1,4-biradical (152) formed by an initial 1,5-cyclization (Scheme 6.67b).766... 

---