Cyclizations initiation

Binucleophiles give regiospecific addition to trifluoromethylacetylene with and without subsequent cyclization. Initial attack by the softer nucleophile occurs preferentially at the carbon p to the trifluoromethyl group [6] (equation 7). 

Cyclizations initiated by C-acylnitrilium ions in synthesis of heterocycles 99X9947. 

The only sesquiterpenes which appear to arise by cyclization initiated by external electrophilic attack (as is common in the di-and triterpenes) are iresin (F) by attack of OH+ and polygodial (G) by attack of H+ (2,7,22,23). 

Scheme 1 5-exo Cyclization initiated by phosphinyl radical addition onto an alkyne... 

The key step in the following synthesis of indenes by the azolide method is an intramolecular C-acylation of a fulvene intermediate. The added dimethylaminopyridine (DMAP) was thought to act as an acyltransfer agent, and diazabicycloundecene (DBU) as cyclization initiator via fulvene deprotonation [116]... 

Another example of an intramolecular cyclization initiated by reactions of an acyliminium ion [32] with an unactivated alkene has been published by Veenstra and coworkers. In their total synthesis of CGP 49823 (1-116), a potent NK antagonist [33], these authors treated the N,O-acetal 1-112 with 2 equiv. of chlorosulfonic acid in acetonitrile to afford acyliminium ion 1-113 (Scheme 1.29) [34]. This is qualified for a cyclization, creating piperidine cation 1-114, which is then trapped by... 

Scheme 32 Radical tandem cyclization initiated by Kolbe electrolysis.

Group 6 allenylidenes also react with the carbon-carbon triple bond of ynamines to yield similar cyclobutenylidene derivatives 88 along with the corresponding alkenyl-aminoallenylidenes 89 (Scheme 32) [286]. These aminoallenylidene complexes result from a formal [2-1-2] cycloaddition between the ynamine C=C and allenylidene Cp=Cy bonds followed by cycloreversion. A stepwise cyclization initiated by the addition of the nucleophilic R C=CNEt2 carbon at the C or Cy position has been proposed in the formation of these isomeric products. As commented previously, unlike their Cr and W counterparts, the reactions of... 

Allenylidenecomplexes 46 also react with thecarbon-carbon triple bond ofynamines to yield similar mononuclear cydobutenyhdene derivatives 48, although mixtures with the corresponding alkenyl-aminoallenylidene spedes 49 are formed (Scheme 2.20) [ 1 Oc]. The former isomer results from the addition of the C=C bond of y namines across the Co,=Cp unsaturation, while the latter is provided bythe formal [2 + 2] cycloaddition between C=C and Cp=Cy bonds and subsequent cycloreversion. In both processes, stepwise cyclization initiated by the addition of the nucleophilic R C=CNEt2 carbon at the Co, or Cy position, respectively, is proposed. Relative proportions of 49 with respect to 48 increase with the electron-releasing capacity of the para-substituents of the diarylallenylidene skeleton (NMe2 > OMe > Me > H). In contrast, the formation of 48 is favored when the reaction is carried out in low polarity solvents. 

Burke et al. [84] synthetised nagilactone F (55) by a polyenic cyclization initiated with acetal and concluded with vinylsilane, giving an overall yield of 6%. The key steps in this synthesis were the coupling of substrates 166 and 167 with control of the absolute and relative stereochemistry, the cationic biscyclization to form the intermediate tricyclic trans-anti-trans 169 and the formation of the D ring by regio-selective intramolecular remote functionalization. 

This reaction is noteworthy for the fact that one chlorine atom of the reagent remains attached to its carbon atom usually either one or all halogen atoms are affected. The reaction sequence of the cyclization (initial S—N or C—N addition) is not established, since intermediate products have so far not been isolated. The known90 superior reactivity of the (S-halogen would suggest the primary formation of A-(trichloro-methanesulfenyl)amidine (68). 

In the course of the reaction, Michael adduct 43 cyclizes initially under base catalysis to the dihydropyridone 45, which forms dianion 46. Electron transfer (an SET process leads to radical anion 47, which is finally transformed into pyridone 44 through an aromati/ation that includes hydrogen transfer and another SET process. 

Tandem cyclizations initiated by an SnH reaction in which subsequent heteroring closure is realized by an intramolecular addition to a multiple bond, a condensation or an SN ipso substitution. 

B. Tandem Cyclizations Initiated by an SnH Reactions 1. Tandem S H Reactions and Addition to Multiple Bonds... 

Scheme 4. Cyclization initiated by photoinduced electron transfer (PET).

Fig. 43 Atom transfer radical addition/cyclizations initiated by Mn2(CO)10...

Krische has reported an unprecedented rhodium-catalyzed tandem conjugate addition/aldol cyclization initiated by a first addition of a boronic acid. The participation of boronic acids in this methodology greatly enhances its synthetic potential owing to their large availability [82]. This catalytic... 

Similar methodology was employed to the synthesis of more complex polycyclic ring system, as shown in Scheme 32 <1997TL9069>. The initial alkenyl radical 54, formed by an intramolecular radical 13-< 4t>-dig macro-cyclization, initiated a radical cascade reaction by first reacting at the a-position of the furan ring. 

During studies on the synthesis of opiates with unnatural stereochemistry, dihydrosinomenine (53a) is often cyclized initially to (+)-dihydrocodeinone (54b). In addition to the desired, 54, the NIH group(159) isolated 10% of a ketone that proved upon recrystallization to be a mixture of 4,5-epoxide (55) and the 5-en-7-one (56). Structures were established by an extensive spectroscopic examination and were confirmed by X-ray crystallographic analysis. In the solid state (+)-4-hydroxy-7-oxo-3-methoxy-17-methyl-5,6-dehydromor-phinan (56), the isomer that crystallizes most readily from ethyl acetate was found to consist of a stack of molecules in the form of an intertwined double helix with strong 0(4)-N hydrogen bonds. The individual helices are not bonded together, except by van der Waals forces. 

Figure 5.7 Proposed mechanism for the cyclization of geranylgeranyl diphosphate (GGPP) to the diterpene copalyl diphosphate, an example of terpene synthase-catalysed cyclization initiated by double-bond protonation, rather than by hydrolysis of the diphosphate ester. PP indicates a diphosphate moiety.

C to —10°C) followed by a Dess-Martin oxidation provided the necessary azidoaldehyde. An intramolecular Staudinger cyclization followed by reduction of the resultant amine provided azepine 364. Treatment of 364 with iodine induced an interesting double cyclization. Initial iodination of the double bond is followed by aziridinium ion formation 365. An intramolecular and stereospecific ring opening by the carboxylate provides the target (—)-stemospironine. 

Scheme 13. 5-exo-dig cyclization initiated after reductive C-I bond cleavage [25]. 

Reaction involving the formation of a sulfonium intermediate (80) followed by a sigmatropic rearrangement was formulated by Trost and Biddlecom (Scheme 8) and cyclization initiated by an allylic copper carbenoid (81) was proposed by Cohen and coworkers (Scheme 9). The common feature of all of these proposed mechanisms relies on the electrophilic addition of the donor to the acceptor prenyl pyrophosphate and is... 

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