Catalyzed Cyclizations

In the previous sections, a number of Ir(I)-catalyzed cycloadditions were described where the oxidative coupling of unsaturated motifs (e.g. alkynes and aUcenes) provides metallacycles as common intermediates. At this point, mention will be made of three examples of Ir(III)-catalyzed cyclizations. 

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A simple acid-catalyzed cyclization transforms i//-ionone into n-ionone (W. Kimel, 1957, 1958). Further treatment with protic acids transforms the tr-ionone to the thermodynamically more stable -ionone. 

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Allyl aryl ethers are used for allylation under basic conditionsfh], but they can be cleaved under neutral conditions. Formation of the five-membered ring compound 284 based on the cyclization of 283 has been applied to the syntheses of methyl jasmonate (285)[15], and sarkomycin[169]. The trisannulation reagent 286 for steroid synthesis undergoes Pd-catalyzed cyclization and aldol condensation to afford CD rings 287 of steroids with a functionalized 18-methyl group 170]. The 3-vinylcyclopentanonecarboxylate 289, formed from 288, is useful for the synthesis of 18-hydroxyestrone (290)[I7I]. 

The (l-ethynyl)-2-propenyl acetate derivative 111 undergoes an interesting PdCl2(PhCN)2-catalyzed cyclization to form the 2-cyclopentenone 112[47], A Pd-carbene complex is assumed to be an intermediate of the formation of 112. 

The cyclization of the enediynes 110 in AcOH gives the cyclohexadiene derivative 114. The reaction starts by the insertion of the triple bond into Pd—H to give 111, followed by tandem insertion of the triple bond and two double bonds to yield the triene system 113, which is cyclized to give the cyclohexadiene system 114. Another possibility is the direct formation of 114 from 112 by endo-rype. insertion of an exo-methylene double bond[53]. The appropriately structured triyne 115 undergoes Pd-catalyzed cyclization to form an aromatic ring 116 in boiling MeCN, by repeating the intramolecular insertion three times. In this cyclization too, addition of AcOH (5 mol%) is essential to start the reaction[54]. 

Pd(II)-catalyzed cyclization of the siloxyhexatriene 34 offers a cyclohexe-none annulation method. The Pd enolate 35, formed by transraetallation of the silyl enol ether with Pd(II), is an intermediate which undergoes intramolecular eWo-alkene insertion. Then Pd(II) is regenerated to give 36, and finally cyclohexenone is formed[38]. 

FIGURE 26 10 The biosyn thetic conversion of squa lene to cholesterol proceeds through lanosterol Lano sterol IS formed by enzyme catalyzed cyclization of the 2 3 epoxide of squalene... 

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

The Lewis acid-catalyzed cyclization of 3-anaino-2-alkerLirnines (21) leads to a wide variety of alkyl- and aryl-substituted quinolines (59). The high regiospecificity and the excellent yields obtained make this process promising. 

In perfumery bisabolol functions as a fixative. The racemic form is manufactured by the acid-catalyzed cyclization of nerohdol (193). 

Another approach uses the reaction of 6-chloro-5-nitropyrimidines with a-phenyl-substituted amidines followed by base-catalyzed cyclization to pteridine 5-oxides, which can be reduced further by sodium dithionite to the heteroaromatic analogues (equation 97) (79JOC1700). Acylation of 6-amino-5-nitropyrimidines with cyanoacetyl chloride yields 6-(2-cyanoacetamino)-5-nitropyrimidines (276), which can be cyclized by base to 5-hydroxypteridine-6,7-diones (27S) or 6-cyano-7-oxo-7,8-dihydropteridine 5-oxides (277), precursors of pteridine-6,7-diones (278 equation 98) (75CC819). 

Diaryl derivatives of the 1,3-oxathiolylium system (29) are prepared by acid-catalyzed cyclization of the /3-keto thioesters (28) which are readily prepared from thioacid salts (27)... 

Application of the above principles to the synthesis of 1,3-diselenolylium ions has been successful. iVjA -Dialkyldiselenocarbamates as their oxo esters (30) undergo acid-catalyzed cyclization and dehydration to give the cation (31) in nearly 90% yield (75JOC746, 77CC505, 80CC866, 80CC866). 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

An example of an exo-dig process would be the base-catalyzed cyclization of an -hydroxy-a,/S-ynone ... 

In agreement with these analyses, it was found that conqiound S was unreactive toward base-catalyzed cyclization to 6, even though the double bond would be expected to be reactive toward nucleophilic conjugate addition. On the other hand the acetylene 7 is readily cyclized to 8 ... 

An example of preferred conrotatory cyclization of four-7c-electron pentadienyl cation systems can be found in the acid-catalyzed cyclization of the dienone 12, which proceeds through the 3-hydroxypentadienyl cation 13. The stereochemistry is that expected for a conrotatory process. 

The first synthesis of 18-crown-6 was reported by Pedersen in his first full paper on erowns . The method used was potassium r-butoxide catalyzed cyclization of hexa-ethlyene glycol monochloride in 1,2-dimethox ye thane, as shown in Eq. (3.7), below. Unfortunately, the yield by this approach was only 1.8%. ... 

A-Nor-B-homo steroids with different substitution patterns than those described above may be prepared by acid catalyzed cyclization of 3)3-hydroxy-5(10)-seco-cholest-tra/w-l(l0)-en-5-one acetate (134a) formed in 30-40% yield by mercuric oxide-iodine sensitized irradiation of cholestane-3j3,5a-diol... 

AB-Dinorsteroids have been prepared by Dauben et al from B-nor-A" -3-ketones by reactions analogous to the sequence (4) - (7). Pyrolysis of the B-nor-2,3-seco diacid anhydride gives the AB-dinor-A -2-ketone in 5 % yield. However, refluxing the diacid with acetic anhydride containing potassium cyanide for 2 days gives the ketone in 50-60% yield, apparently by base-catalyzed cyclization of an intermediate bis-acylcyanide. 

Ryder reported the preparation of an interesting alkyl diaryl furan that was subsequently polymerized and studied as a conducting polymer. The monomer furan 49 was available fron the acid catalyzed cyclization of dione 48. ... 

Further elaboration of 152 resulted in the synthesis of (derived from the reduction of pyridinium salt 150b with excess of LiAlFt4 in THE Acid-catalyzed cyclization of 154 led to indoloquino-lizidine 155 (25% yield from 150b), a precursor of deplancheine (80TL2341) (Scheme 5). 

Transition metal-catalyzed cyclizations of heterocycles accompanied by multiple bonds migration 98SL1. 

Palladium(II)-catalyzed cyclization of N-alkylation of allyl alcohols by ure-tanes and its application to the synthesis of natural saturated heterocycles 98YGK34. 

Transition metal-catalyzed cyclizations accompanied by multiple bond migration with formation of heterocycles 98SL1. 

Compound 68 can also be obtained by an acid-catalyzed cyclization of 42, which was prepared by the Michael addition reaction of 39 to mesityl oxide as shown in Section IV.A. As for the product 69, the presence of the tosyloxy group at the 5 position instead of the 6 position is determined, utilizing the anisotropy effect of the 1-acetyl group to the C-7 proton, by comparing its H NMR spectrum with that of 70, obtained in 69% yield by the treatment of 69 with NaH and AcCl. 

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