Radicals unsaturated, cyclization

The catalytic conditions are well suited for the preparation of cyclopropanes provided that a, /J-unsaturated carbonyl compounds are employed as radical acceptors (formation of electrophilic radicals after cyclization) as shown in Scheme 32 [123]. 

A radical tandem cyclization, consisting of two radical carbocyclizations and a heterocoupling reaction, has been achieved by electrolysis of unsaturated carboxylic acids with different coacids. This provides a short synthetic sequence to tricyclic products, for example, triquinanes, starting from carboxylic acids which are accessible in few steps (Scheme 6) [123]. The selectivity for the formation of the tricyclic, bi-cyclic, and monocyclic product depending on the current density could be predicted by applying a mathematical simulation based on the proposed mechanism. 

Unsaturated carboxylic acids can be de-carboxylated to alkyl radicals that undergo an intramolecular addition. The S-exo-trig-cyclization of fi-allyloxy radicals, generated from an appropriate carboxylic acid, combined with a final heterocoupling has been applied to synthesize a precursor of prostaglandine PGF2q (Fig. 47) [246] and a branched carbohydrate (ratio of diastereo-mers 1.8 1) (Fig. 48) [247]. A radical tandem cyclization of a doubly unsaturated monocyclic carbocyclic acid provides a... 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

C. S. Wilcox and L. M. Thomasco, New syntheses of carbocycles from carbohydrates. Cycliza-tion of radicals derived from unsaturated halo sugars, J. Org. Chem. 50 546 (1985) see also S. Hanessian, D. S. Dhanoa, and P, L. Beaulieu, Synthesis of tt-substituted a,P-unsaturated esters via radical-induced cyclizations, Can. J. Chem. 65 1859 (1987). 

These radical cations, if possessing (S, -unsaturation, cyclize to give 5-membered rings 97, Scheme 41, and thus provide a... 

More recently 2,3-dihydro-4-methyl-2-thioxo-3-thiazolyl alkenylcarbamates were shown to be useful precursors of monoalkylaminium radicals23, and amidyl radicals were generated from 1,2-dihydro-2-thioxo-l-pyridinyl imidates24. Both radicals, which contain <5,e-unsaturation, cyclize in a 5-exo fashion, but examples of stereoselective cyclization have not yet been reported. 

Similarly, at a carbon anode in 1 1 MeOH-THF, anodic cyclization of allylsilane enol ether (XCIX) proceeded stereoselectively to give (C) [Eq. (63)]. The use of allyl silanes as the unsaturated nucleophilic component in such radical-cation cyclizations proved to be beneficial, though the exact mechanistic details remain somewhat speculative [147]. The method represents an improvement over earlier methods involving anodic cyclization of alkenyl-substituted enol acetates [148]. 

A radical tandem cyclization, consisting of two radical additions and a heterocoupling reaction, has been achieved by coelectrolysis of unsaturated carboxylic acids with different coacids. This provides a short synthetic sequence to tricyclic products, such as... 

The photooxidation of m-unsaturated a-alkylsilylamines by the singlet excited state of DCN proceeds with selective desilylation to generate a-amino radicals from a-alkylsilylamine radical-cation. Cyclization of the a-amino radicals leads to substituted pyrrolidines and piperidines [42] (Scheme 20). 

Scheme 15. Radical-chain cyclization of unsaturated acetals using polarity reversal catalysis...

As further extension of radical-mediated cyclization, (-)-steganone was ster-eoselectively synthesized by an intramolecular reductive coupling between aldehyde and a,p-unsaturated y-lactone moiety of biphenyl mono Cr(CO)3 complex 14 (Eq.lO) [10]. 

Hanessian S, Dhanoa DS, Beaulieu PL (1987) Synthesis of carbocycles from m-substituted a,p-unsaturated esters via radical-induced cyclizations. Can J Chem 65 1859-1866... 

Thiol-catalyzed Radical-chain Cyclization of Unsaturated Acetals and Thioacetals. When the unsaturated dioxolane 1 and a radical initiator, 2,2-di(t-butylperoxy)butane (DBPB), were heated at 125 °C in octane in the presence of tri(f-butoxy) silanethiol (TBST), the spirocyclic ketal 2 was formed cleanly and isolated in 92% yield (eq 1). When the reaction was performed in the absence of TBST, compound 2 was not detected. TBST is... 

The first proposal of intramolecular addition of 5-hexenyl radicals was independently reported in 1957 by Marvel and by Butler. They polymerized 1,6-dienes and, finding that the products were devoid of unsaturation, assumed that the initially produced radicals had cyclized their work will be discussed in a later section. Also to be discussed is the pioneering work of Friedlander who, in 1958, reported the cyclization of diallyl ethers and diallyl thioethers under free radical conditions. 

Radical-induced cyclizations have been used to prepare thiolans of the type (16), the unsaturated thiol precursors being prepared by the reaction of allyl-... 

The and e values of the aHyl group in DAP have been estimated as 0.029 and 0.04, respectively, suggesting that DAP acts as a fairly typical unconjugated, bifunctional monomer (42). Cyclization affects copolymerization, since cyclized radicals are less reactive in chain propagation. Thus DAP is less reactive in copolymerization than DAIP or DATP where cyclization is stericaHy hindered. Particular comonomers affect cyclization, chain transfer, and residual unsaturation in the copolymer products. DiaHyl tetrachloro- and tetrabromophthalates are low in reactivity. 

Unsaturated ketones react with phenyUiydrazines to form hydrazones, which under acidic conditions cyclize to pyrazolines (35). Oxidation, instead of acid treatment, of the hydrazone with thianthrene radical cation (TH " ) perchlorate yields pyrazoles this oxidative cyclization does not proceed via the pyrazoline (eq. 4). 

Intramolecular addition reactions are quite common when radicals are generated in molecules with unsaturation in a sterically favorable position. Cyclization reactions based on intramolecular addition of radical intermediates have become synthetically useful, and several specific cases will be considered in Section 10.3.4 of Part B. 

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