Intramolecular Couplings

Ignasiak et al. (1975) also measured the infrared spectra of (Z)- and ( diazo-cyanides and demonstrated clearly that neither of the isomers was identical with the corresponding diazoisocyanide (Ar-N2-NC, see Sec. 6.4), as proposed at the beginning of this century. 

Ahern and Gokel (1979) claim that diazocyanides can be prepared by stirring arene-diazonium tetrafluoroborates with one equivalent of KCN (solid) and 0.05 equivalent of 18-crown-6 in CH2C12 for some hours. The authors did not, however, investigate whether the products, obtained in good yields, are the (Z)- or the (ii)-isomers. 

Lewis and Suhr (1959 b) measured the influence of substituents on the rate of formation and the equilibrium of (jE )-benzenediazocyanide. Ritchie and Wright (1971 b) used the stopped-flow technique to determine the rate constants of formation and the equilibria of substituted (Z)-benzenediazocyanides in water, and also later in methanol. 

Those processes that can be described as intramolecular coupling belong to the same type of reaction as discussed thus far in this chapter. Intramolecular N-, O-, S-, and C-coupling reactions are known. The older literature on such ring closure reactions is particularly extensive. We will discuss only a few representative examples published in the last two decades. The older literature was reviewed briefly by Wulfman (1978, p. 277) and, in more detail, by Saunders and Allen (1985, Chap. 8). 

In intramolecular N-coupling the diazonio group interacts with a nitrogen-containing substituent in the ortho-position of the aromatic ring. This is the cause of the difficulties in the diazotization and bisdiazotization of 1,2-diaminobenzene (6.45, 

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Quack M 1982 The role of intramolecular coupling and relaxation in IR-photochemistry Intramolecular Dynamics, Proc. 15th Jerusalem Symp. on Quantum Chemistry and Biochemistry (Jerusalem, Israel, 29 March-1 April 1982) ed J Jortner and B Pullman (Dordrecht Reidel) pp 371-90... 

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

The cyclized products 393 can be prepared by the intramolecular coupling of diphenyl ether or diphenylamine(333,334]. The reaction has been applied to the synthesis of an alkaloid 394[335]. The intramolecular coupling of benzoyl-A-methylindole affords 5-methyl-5,10-dihydroindenol[l,2-b]indol-10-one (395) in 60% yield in AcOH[336]. Staurosporine aglycone (396) was prepared by the intramolecular coupling of an indole ring[337]. 

Synthesis of camptothecin (163) is another example[133]. The iboga alkaloid analog 164 has been synthesized smoothly by the intramolecular coupling of iodoindole and unsaturated ester to form an eight-membered ring. Af-Methyl protection of the indole is important for a smooth reaction[134]. An efficient construction of the multifunctionalized skeleton 165 of congeners of FR900482 has been achieved[135]. 

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

The allylstannane 474 is prepared by the reaction of allylic acetates or phosphates with tributyltin chloride and Sml2[286,308] or electroreduction[309]. Bu-iSnAlEt2 prepared in situ is used for the preparation of the allylstannane 475. These reactions correspond to inversion of an allyl cation to an allyl anion[3l0. 311], The reaction has been applied to the reductive cyclization of the alkenyl bromide in 476 with the allylic acetate to yield 477[312]. Intramolecular coupling of the allylic acetate in 478 with aryl bromide proceeds using BuiSnAlEti (479) by in situ formation of the allylstannane 480 and its reaction with the aryl bromide via transmetallation. (Another mechanistic possibility is the formation of an arylstannane and its coupling with allylic... 

Tb allium (ITT) ttifluoroacetate promotes olefin cyclization reactions and intramolecular coupling reactions (32,33). 

From the intramolecular coupling product, just the two MEM-groups protecting the phenol functions (MEM = 2-methoxyethoxymethyl) have to be removed, in order to obtain the target molecule. 

One of the first reactions to be carried out in a molten salt (albeit at 270 °C) was the Scholl reaction. This involves the inter- or intramolecular coupling of two aromatic rings. A example of this reaction, in which 1-phenylpyrene was cyclized to indeno[l,2,3-cd]pyrene [26] is given in Scheme 5.1-7. A more elaborate version of the Scholl reaction is shown in Scheme 5.1-8 and involves bicyclization of an aromatic cumulene [27]. 

The diazonium salt 2 derived from 2-(3-hydroxyphenoxy)aniline (1) undergoes an intramolecular coupling reaction to yield the dibenzoxadiazepinol 3.153... 

Intramolecular coupling of the easily prepared 12-membered bis(imine) 1 can be used to synthesize the highly annulated 1,4-diazocine 2.12... 

Diazotization and intramolecular coupling of suitable aromatic amines can also be used for the synthesis of 1,2,5-triazocines.12... 

Reduction of the nitro group in 70 with zinc in hot sodium hydroxide results in formation of pyrrolo[2,l-(f][l,2,5]benzotriazepine 71 by intramolecular coupling of the amino group with the newly formed nitroso group (Scheme 16). If the reduction is carried out under the less rigorous conditions of zinc in aqueous ammonium chloride the intermediate hydroxy compound is formed <96T10751>. 

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