Acetalization-cyclization

The acetal 1, obtained from salicylamide and bromoacetaldehyde diethyl acetal, cyclizes on heating to provide l,4-benzoxazepin-5(4//)-one (2).32... 

Hydrochlorides of. V-(2-cyanovinyI)benzene-l,2-diamine, prepared from benzenc-1,2-diamine and (ethoxymethylene)malononitrile or ethyl cyano(ethoxymethylene)acetate, cyclize to salts of 3//-l,5-benzodiazepin-2-amine 1 on heating.254a b... 

In 2007, Womack et al. published the conversion of 2-aUcylcinnamyldehydes to 2-aLkylindanones via a catalytic intramolecular Friedel-Crafts reaction. In the presence of 5-10 mol% FeCls different in situ generated ( )-2-alkylcinnamaldehydes-derived dimethyl acetals cyclized to l-methoxy-2-aIkyl-7//-indenes in good to high yields (Scheme 6) [22]. The transformation corresponds to a formal intramolecular Friedel-Crafts acylation which is achieved with catalytic quantities of Lewis acid. This result is in strong contrast to traditional Friedel-Crafts acylations which require stoichiometric amounts of Lewis acid. 

Rhodium-catalyzed diazo insertions, known since 1976, have been extensively reviewed39. The first report40 indicated that rhodium acetate efficiently catalyzes diazo insertion into an alkene, giving the cyclopropane. Rhodium-catalyzed intramolecular C-H insertion was first observed by workers at Beecham Pharmaceuticals, who reported that 1, on exposure to a catalytic amount of rhodium acetate, cyclizes cleanly to the /1-lactam41. This approach to thienamycin derivatives has been developed further by these workers42,43. 

Among the methods available for the synthesis of the pyridine system, Hantzsch synthesis is probably the most important and widely used synthetic route. However, the pyridine ring can be synthesized from the reaction between pentan-2,4-dione and ammonium acetate. Cyclization of 1,5-diketones is also considered as a convenient method for the synthesis of corresponding pyridine derivatives. Commercially, pyridine is obtained from distillation of coal tar. 

Few examples of intramolecular enol silyl ether or silyl ketene acetal cyclizations to oc,3-enones have been reported. Notable, as exemplified in Scheme 34, is the iodotrimethylsilane-mediated intramolecular cyclization of 5-(iodoacetoxy)-a,3-enones (211) to 5-lactones (214). These cyclizations proceed with in situ generated silyl ketene acetals (212) arising from iodotrimethylsilane reduction of the iodoacetoxy moiety.87... 

The /3-aminoester 385, synthesized by coupling of a chiral imine with a ketene acetal, cyclized toward cis-3-hydroxy-4-phenylazetidin-2-one 386 in the presence of boron tribromide (Scheme 57) <1998BML1619>. 

In the context of a chemical study related to problems of vitamin B12 biosynthesis, peripheral C-methylation of the magnesium complex of tctct-OEPc (17) was reported to yield a mixture of isomeric products (18a-c) (83AG(E)631). A similar reaction was found to occur at C-12 of nonamethyl pyrrocorphin (19). One of the by-products of this reaction is the seco-corphinoid derivative 20, which, on complexation with Ni(II) acetate, cyclizes to give an Ni(II) corrinate (21) (84CC583). 

This result argued for the alternate view of the EEC Cp mechanism sequence, involving initial face-selective attack on the chiral radical-cation intermediate by methoxyl radical (path A), followed by acetal cyclization and proton loss. A rationale for the increased chemical yields observed for the systems studied in Eqs. (44) and (45) was not addressed in this work, although intramolecular solvation and stabilization of the intermediate radical cation by the appended hydroxyether side chain was suggested as one of the possible factors involved in the observed stereodifferentiation [101,102]. 

Analogous systems related to the models for allylsilane-acetal cyclizations have been studied. In these cases, however, cyclizadon of the acetals (105 Scheme SO) fonts the corresponding syn and anti bicyclic ethers (106). The audiors concluded diat the stereochemistry of cyclizadon of acetal models (105) is dependent upon the mechanism of activation. In the presence of TMS-OTf the acetals (105 -c) reacted through an SN2-type process, while the isopropyl acetal (105d) reacted through prior ionization to oxonium ion (107). 

Imbach et al. have reported syntheses of 4 -thiothymidine (104) and 4 -thiouridine (105) starting fromL-lyxose, following the dithiobenzyl acetal cyclization method and the Hilbert-Johnson silyl condensation reaction of 103 with silylated thymine (77% yield, a p 43 57) and uracil (74% yield, a 47 53),... 

Aminothiophenol is cyclized by reaction with prop-2-ynyltriphenylphos-phonium bromide, but some 2-substituted anilines give the phosphonium salt (a possible intermediate in the thiophenol reaction) which may be cyclized separately (see Chapter 16, Section I.S) [2736]. Reaction of thiophenols with the lactonic 2-oxazolin-S-ones can give any one of three products in acetic acid-sodium acetate, cyclization to the thiazole occurs while in some other solvents, acylamino and acylthio products are formed, and may be cyclized by acetic acid-sodium acetate [3088]. 

The homoallylic acetal radical cyclization product reported by Stork [55] was later used in the construction of a significant portion of the gelsemine structure [76]. Further examples for homoallylic acetal cyclization exhibiting useful stereoselectivity include the (-)-protoemetinol synthesis by Fukumoto [77] and the rhizoxin partial syntheses by Rama Rao [78] and White [79]. In the synthesis of (+)-12b-epidevinylantirhine (117) [80] (Scheme 40), Ihara adopted low-temperature conditions for radical cyclization of the chiral unsaturated ester 114 in the presence of MAD. The lactone 116 in high diastereomeric excess was obtained from the cycli-... 

Free radical cycUzations. Cobaloxime in combination with a sacrificial Zn foil anode has been used to effect the reductive generation of carbon-centered radicals from bromoacetals in electrochemical proces.ses. When an unsaturated side chain is present in such acetals, cyclization may occur. 

Optically active tetrahydropyran derivatives can be obtained by domino cross aldol/acetal cyclization reaction of aromatic aldehydes with glutaraldehyde generated from the inexpensive tetrahydro-2/f-pyran-2,6-diol under equilibrium conditions, in yields ranging from 42% to 78% and good diastereo- (60-75% de) and enantioselectivities (93-99% ee) [75],... 

Chiral allene 49 und oes a pall8dium(ll)-mediated acetalization-cyclization-methoxycaibonylation in the presence of acid and water scavengers to afford compound 50 (see Vol. 

The conversion of 4,5-hexadienoic acids to furanones and of 4,5-hexadienals to furanosides was achieved in a one-pot acetalization-cyclization-methoxycarbonylation procedure (Scheme 21). Trialkylsiloxy substituents in /3-position induce high stereo selectivities. This method was applied in a synthesis of nucleoside analogs bearing a branched difunctional side chain. ]... 

The critical comparisons between TMSOTf-induced acetal cyclization and TfOH-induced enol ether cyclization are combined in Table V. For clarity only the Z-isomers of 14 are included. Since we assume that reactions of 14 must proceed through the oxocarbenium ion i we conclude that, based on the disparity in stereochemical results, reactions of methyl (5a), ethyl (5b) and most likely also isobutyl (5c) acetals do not occur via an S l mechanism. However, the similarity in stereochemical outcome in the isopropyl series (d) strongly suggests that 5d does, to a large extent, react via an S l mechanism. 

The silyl enol ethers (42), in the presence of palladium acetate, cyclize to give the a,/8-unsaturated ketones (44), the reaction probably proceeding via the oxo-ir-allylpalladium complex (43)/ The reaction proceeds readily at room temperature in the presence of stoicheiometric amounts of Pd(OAc)2, and is particularly useful for the synthesis of 3-methylcyclopent-2-enone derivatives (45). 

Aminopyrimidyl-acetaldehydes and -acetones prepared by hydrolysis of their acetals cyclize spontaneously to pyrrolo[2,3-d]pyrimidines.—E 4-Amino-5-(2,2-diethoxyethyl)-2,6-dihydroxy pyrimidine shaken 24 hrs. with 1.5 equivalents of 0.2 N HCl 2,4-dihydroxypyrrolo[2,3-d]-pyrimidine. Y 93%. F. e. and method s. J. Davoll, Soc. I960, 131. 

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