Cyclization reactions carbonyl derivatives

Reactions of acetylene and iron carbonyls can yield benzene derivatives, quinones, cyclopentadienes, and a variety of heterocycHc compounds. The cyclization reaction is useful for preparing substituted benzenes. The reaction of / fZ-butylacetylene in the presence of Co2(CO)g as the catalyst yields l,2,4-tri-/ f2 butylbenzene (142). The reaction of Fe(CO) and diphenylacetylene yields no less than seven different species. A cyclobutadiene derivative [31811 -56-0] is the most important (143—145). 

During hydrogenation, intermediate aromatic hydroxylamines may undergo various cyclization reactions in molecules containing a suitably disposed carbonyl group, or carbonyl derivative, such as an oxime (13). The cyclized product may or may not maintain the N—OH bond, depending on the solvent, the catalyst, and the electrophilicity of the carbonyl (27,28,29,32,67,68). 

The reduction of aromatic nitro compounds to amino derivatives and cyclizations to various heterocyclic compounds are presented in Chapter 9. Recent advances are presented here. Reaction of 2-nitrobenzaldehyde with vinyl carbonyl compounds in the presence of 1,4-diazbi-cyclo[2.2.2]octane affords Baylis-Hillman products, the catalytic reduction of which results in direct cyclization to quinoline derivatives (Eq. 10.78).134... 

Alkoxides that arise from simple carbonyl additions have also functioned as excellent in situ nucleophiles for intramolecular hydroalkoxylation reactions. Garbinols derived from the addition of allyltin reagents have proved to be potent nucleophiles in reactions of this type (Equation (99)),349 and this approach has also been used for the combined addition-cyclization of alkynals under Pd(n)350 or Cu(i)351 catalysis, and alkynones under Pd(n) catalysis.352... 

A survey of Wacker-type etherification reactions reveals many reports on the formation of five- and six-membered oxacycles using various internal oxygen nucleophiles. For example, phenols401,402 and aliphatic alcohols401,403-406 have been shown to be competent nucleophiles in Pd-catalyzed 6- TZ /fl-cyclization reactions that afford chromenes (Equation (109)) and dihydropyranones (Equation (110)). Also effective is the carbonyl oxygen or enol of a 1,3-diketone (Equation (111)).407 In this case, the initially formed exo-alkene is isomerized to a furan product. A similar 5-m -cyclization has been reported using an Ru(n) catalyst derived in situ from the oxidative addition of Ru3(CO)i2... 

It is worth mentioning that in a few cases the (3-elimination of the silyl radical from the a-silyl alkoxyl radical (47) with the formation of corresponding carbonyl derivative was observed [63,64]. Evidently the fate of a-silyl alkoxyl radical depends on the method of radical generation and/or the nature of the substrate. Two examples that delineate the potentialities of this rearrangements are reported in Reactions (5.33) and (5.34). In the former, the 5-exo cyclization of secondary alkyl radical on the carbonyl moiety followed by the radical Brook rearrangement afforded the cyclopentyl silyl ether [65], whereas Reaction (5.34) shows the treatment of an a-silyl alcohol with lead tetracetate to afford the mixed acetyl silyl acetal under mild conditions [63]. 

Padwa and Prein (105,106) applied chiral, but racemic, isomiinchnone dipoles in diastereoselective 1,3-dipolar cycloadditions. The carbonyl ylide related isomiinch-none derivative rac-70 was obtained from the rhodium-catalyzed cyclization of diazo-derivative rac-69 (Scheme 12.24) (105). The reactions of the in situ formed dipole with a series of alkenes was described and in particular the reaction with maleic acid derivatives 71a-c gave rise to reaction with high selectivities. The tetracyclic products 72a-c were all obtained in good yield with high endo/ exo and diastereofacial selectivities. In another paper by the same authors, the reactions of racemic isomilnchnones having an exo-cyclic chirality was described (106). 

Gopalan, A. S. Intramolecular cyclization reactions of carbonyl derivatives of hydroxy-sulfones. Tetrahedron 2002, 58, 3737-3746. 363... 

The high stereoselectivity observed in this cyclization reaction was attributed to the location of the carbonyl moiety in a rigid cyclic ring framework, allowing H-abstraction from the same face of the initially formed five-membered ring. The same group has further utilized the constraint imparted by the benzylidene acetal moiety on the excited state photoreactivity of the carbonyl moiety of the D-xylose derivative 52. Thus, 8-H-abstraction results in the formation of a diastereomeric mixture of cyclized product 53, which is further transformed into D-glucopyranose 54 and D-idopyranose 55 derivatives, as shown in Scheme 8.16 [17]. 

In intermolecular PET processes, radical ions are formed either as close pairs or as free species from neutral molecules (Sch. 1) [2,6]. Most commonly, carbonyl compounds or related derivatives as for example enol ethers, cyclopropyl ketones, and siloxycyclopropanes are used for intramolecular cyclization reactions. With the exception of cycloadditions the ring-building key step is always an intramolecular bond formation. In PET... 

As reported in Figure 2.5, nitroolefins (26), easily obtained by nitroaldol condensation between 5-nitro ketones (24) and aldehydes (25), are converted directly into the spiroketals (29) by reduction with sodium boronhydride in methanol. The one-pot reduction-spiroketalization of nitroalkenes (26) probably proceeds via the nitronate (27) that by acidification is converted into carbonyl derivatives, which spontaneously cyclize to emiketals (28). Removal of the tetrahydropyranyl group, by heating the acidic mixture during the workup, affords, in a one-pot reaction from (26), the desired spiroketals in 64-66% overall yields. The spiroketalization of (26)-(29b) proceeds in high ( )-diastereoselectivity. 

The cyclizations of 85 to 86 and of 87 to 88 represent the simple cases in which the internal nucleophile is the OH group of an alcohol [64,65]. An in situ generated hydroxy group, as in the addition of alcohols to carbonyl compounds, can also participate in phenylseleno-etherification reactions. This is examplified by the conversion of 89 into 90 in the presence of benzyl alcohol [66]. Another type of OH, which gives rise to these reactions is the enolic OH of /1-dicarbonyl compounds. Thus, Ley reported that compounds like 91 and 93 can be transformed into the cyclic derivatives 92 and 94 by treatment with N-PSP 11 in the presence of zinc iodide [67]. The cyclization of 95 to 96 represents a simple example of the selenolactonization process [68, 69]. It is interesting to note that the various cyclization reactions indicated in Scheme 14, which require different electrophilic selenenylating agents, can all be effected with phenyselenyl sulfate [70]. 

Dihydro-l,3-selenazol-4-one derivatives 31 are prepared by the reaction of primary selenoamides with a-haloacyl halides in the presence of pyridine. The cyclization reaction is thought to involve an Sn2 substitution reaction. Steric factors at the a-position of the carbonyl carbon of a-haloacyl halides slow the attack by selenium (Equation 16) <2003HAC106, 2002S195>. 

The preparation of a poly-a-amino acid involves first, synthesis of the monomer, and secondly its polymerization. We are mainly concerned here with the latter aspect. Methods of monomer synthesis commonly follow one of two alternative routes viz. reaction of the a-amino acid with phosgene (1) or cyclization of an N-alkoxy carbonyl derivative of the a-amino acid by treating with SOCI2, PCI5 or similar reagents (2). 

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