Intramolecular cyclization, of hydroxy

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

All hemiacetals are formed by nucleophilic addition of a hydroxy group to a carbonyl group. In the same way, cyclic hemiacetals are formed by intramolecular cyclization of hydroxy aldehydes. 

Indanedione derivatives in synthesis of heterocycles 80MI50. Intramolecular cyclization of hydroxy- and mercaptonitriles as a method of... 

The intramolecular cyclization of hydroxy ketones and thioketals, performed under mild conditions, is often used to produce oxygen-containing medium-ring size heterocycles. Upon treatment with silver perchlorate... 

The intramolecular cyclization of 2-alkynylaryldiazonium salts (Richter reaction) leads not only to 4-hydroxy- but also to 4-bromo- and 4-chlorocinnolines. The behavior of alkynylpyrazolediazonium chlorides differs from that of their benzene analogs. The Richter reaction of the series of alkynylaminopyrazoles gives only 4-halo derivatives of l//-pyrazolo[3,4-c]pyridazines and l//-pyrazolo[4,3-c] pyridazines, and mainly hydroxy derivatives of 2//-pyrazolo[3,4-c]pyridazines. 

The Parham cyclization of the iodinated imide 270 by BuLi in dry THF at —78°C afforded 1 lZ -hydroxy-l,3,4,6,7,l lZ -hexahydro[l,4]oxazine[3,4-a]iso-quinolin-4-one 258 (97JOC2080). Iodide-lithium exchange was faster then addition to the carbonyl group of imide 270 and intramolecular cyclization of the initially formed anion gave compound 258. 

As attractive as the transannular bridging of bis(thiolactones) to bicyclic bis(oxepane) frameworks is, our inability to convert the disulfide bridging product (see 25, Scheme 5) to a mmv-fused bre-vetoxin-type bis(oxepane) (see 28) necessitated the development of a modified, stepwise strategy. This new stepwise approach actually comprises two very effective methods for the construction of cyclic ethers the first of these is the intramolecular photo-induced coupling of dithioesters, and the second is the reductive cyclization of hydroxy ketones. We will first address the important features of both cyclization strategies, and then show how the combination of the two can provide an effective solution to the problem posed by trans-fused bis(oxepanes). 

A stmple and general synthesis of 2,2,4,5-tetrasubstituted furan-3(2//)-ones from 4-hydroxyalk-2-ynones and alkyl halides via tandem CO, addition-elimination protocol is described <96S 1431>. Palladiuni-mediated intramolecular cyclization of substituted pentynoic adds offers a new route to y-arylidenebutyrolactones <96TL1429>. The first total synthesis of (-)-goniofupyrone 39 was reported. Constmction of the dioxabicyclo[4.3.0]nonenone skeleton was achieved by tosylation of an allylic hydroxy group, followed by exposure to TBAF-HF <96TL5389>. 

The intramolecular cyclization of diketo-enals and keto-enals was accomplished by the combination of a cationic Rh complex and fn(2-furyl)phos-phine (2 - Fur3P). The corresponding bicyclic hydroxy-aldehydes were produced in good to excellent yields, as demonstrated by the formation of 74,76 and 78 (Scheme 22) [36]. 

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

Pyrrolo[l,2- ][l,2]oxazines are a class of compounds with very few references regarding synthesis and reactivity. An interesting preparation has been described by intramolecular cyclization of IV-hydroxy pyrrolidines carrying a methoxyallene substituent at C-2 (242, Scheme 32). These compounds were obtained by addition of a lithiated allene to chiral cyclic nitrones 241. Cyclization occurred spontaneously after some days at relatively high dilution (0.05 M). Compounds 243 (obtained with excellent diastereoselectivity) can be submitted to further elaboration of the double bond or to hydrogenolysis of the N-O bond to form chiral pyrrolidine derivatives (Section 11.11.6.1) <2003EJ01153>. 

In a similar manner, intramolecular cyclization of the O-stannyl ketyl derivatives 201 and 206, generated from the oxazolyl aldehydes 200 and 205, provides a facile method for the chiral synthesis of 3-hydroxy-2-(hydroxymethyl)-5-substimted-pyrrolidines 202 and 203 and the piperidine analogues 207 and 208 that can be successfully transformed into naturally occurring amino alcohols, (+)-bulgecinine 204 and (—)-desoxoprosopinine 209, respectively (Fig. 

The application of the Friedlander reaction to 3-aminopyridine-2-carbaldehyde (135) gives good yields of the 2,3-disubstituted 1,5-naphthyridines (136) (75CR(C)(280)38l). The intramolecular cyclization of /3- (3-aminopyridinyl)acrylic acid (137) results in the formation of l,5-naphthyridin-2-one (138) (66JHC357), whilst the condensation of 3-aminopyridine-2-carboxylic acid or its esters (139) with active methylene compounds yields 4-oxo (132) and 4-hydroxy-2-oxo compounds (134 R = H) after hydrolysis and decarboxylation of the intermediates (140) and (134 R = C02Et). Reductive cyclization of the 3-nitropyridine derivative (141) gives the 1,5-naphthyridine (142) (71JOC450). 

Cyclization of hydroxy acids 0-24 Cyclization of halo acids 0-89 Intramolecular coupling 2-43 Cleavage of cyclic a-cyano ketones 5-4 Internal addition of alcohols to a ke-tene function... 

The hexahydropyrimidine (58), formed from l-phenylpropane-l,2-dione and propane-1,3-diamine, is an excellent precursor for the a-diimine macrocyclic complexes (60), presumably via the amino ketone (59) (Scheme 36).126 In this case, intramolecular cyclization of (59) to (58) is reversible, so that the metal ion can exert a thermodynamic template effect in formation of the complex (60). This represents a further example of a long-known phenomenon in which a metal ion can stabilize an a-diimine structure by virtue of the formation of stable five-membered chelate rings. Many 2-hydroxy- or 2-mercapto-amines undergo reaction with a-dicarbonyl compounds to yield heterocyclic compounds rather than a-diimines. However, in the presence of suitable metal... 

This cleavage reaction can be used to effect intramolecular homologated cyclization of hydroxy allylsilanes by conversion to the 2-methoxyethoxymethyl (MEM) ether (7, 228-229) followed by cleavage with TiCl4 to the species 6=CH2. 

A2-Oxazolines. The intramolecular cyclization of /1-hydroxy hydroxamates to /1-lactams by P(C6H5)3-CC14 (10,447-448) can be used for cyclization of a carboxylic acid and a /1-amino alcohol to form a d2-oxazoline (equation I).1... 

Cyclization of hydroxy epoxides to tetrahydrofurans or tetrahydropy-rans.1 CSA is the most efficient and convenient catalyst for this intramolecular epoxide opening. The cyclization of trans-epoxides is particularly useful because it can lead to either 5- or 6-membered cyclic ethers as shown in equation (I) and (II). 

Several indium-mediated intramolecular carbonyl allylation reactions have been investigated, and it has been found that these reactions provide an easy access to a variety of cyclic compounds. The intramolecular cyclization of 49a-c mediated by indium in aqueous media proceeds smoothly to afford carbocyclic systems containing y-hydroxy-Q -methylene esters 50a-c, which either spontaneously or readily cyclize to give fused o -methylene-y-butyrolactones 51a-c (Scheme 52). The same cyclization of 49d is too slow to compete with the side-reaction, in which the bromide is substituted by a hydroxy group. The ring junction stereochemistry of fused lactones 51 has been found to be cis in all cases. Of the two possible transition states, the one leading to the m-fused compounds is preferred, because the chair-chair conformation is favored over the chair-boat conformation.209... 

A useful extension of the alkoxycarbonylation reaction has been devised in order to obtain 3,4-dihydro-4-hydroxy-l//-2-benzopyran-3-acetic acid lactones from 5-alkene-l,4-diols. The intramolecular cyclization of 7, carried out with palladium(II) acetate and copper(II) chloride under a carbon monoxide atmosphere, affords the m-lactone 8 in 68% yield. The configuration is assigned on the basis of H-NMR double resonance methods86. 

Problem 21.38 What lactol (cyclic hemiacetal) is formed from intramolecular cyclization of each hydroxy aldehyde ... 

Intramolecular cyclization of a hydroxy aldehyde forms a hemiacetal with a new stereogenic center, so that an equal amount of two enantiomers results. 

An intramolecular cyclization of -hydroxysulfoxides effected by At-chloro-succinimide, A bromosuccinimide, or sulfuryl chloride gives 1,2-oxathietane 2-oxides, for example, 496, via a sulfoxonium salt. These cyclic sulfoxonium intermediates have been suggested in the conversion of /3-hydroxy-sulfoxides to /3-chlorosulfones, and to a,j3-unsaturated sulfones, in the conversion of /3-ethoxycarbonylsulfoxides to alkenes and of /3-hydroxysulfides to /3-hydroxysulfoxides, and in the conversion of 3-hydroxy- 3-vinylsulfoxides (e.g., 497) to useful terpene building blocks. The yields of the products from 497 vary somewhat depending on the stereochemistry about the two chiral centers. The more highly substituted 1,2-oxathietane 2-oxides are the most stable, because of... 

A naphthoxathiete 2,2-dioxide has been suggested as being derived by an intramolecular cyclization of l-hydroxy-2,3,4,6-naphthalenetetrasulfonic acid. ... 

The electrochemical oxidation of the aspidofractinine-type alkaloid kopsingine in a dichloromethane/acetonitrile medium at a platinum anode in the presence of 2,6-lutidine results in the intramolecular cyclization of an hydroxy group to the intermediate iminium ion of the tertiary amine structure. Thus, kopsidine A was formed in 72% yield [19]. 

Tetrahydrofurans, synthesis via intramolecular cyclization of unsaturated hydroxy compounds 82KGS1443. 

Yet another reaction used in the synthesis of 2,7-naphthyridine derivatives involves intramolecular cyclization of enamino nitriles under the action of acid catalysts. Thus compound 153 underwent cyclization to form 1-hydroxy-2,7-naphthyridine 154, used in the synthesis of sedative agent 155 (1988USP4859671). 

With the success of reducing nitriles in the presence of a 1,3-diamine to make hexahydropyrimidines, we turned our attention to the use of 3-hydroxy-1-aminopropane (22) as a surrogate for the 1,3-diamine. Hydrogenation of aceton-trile with Raney Ni in the presence of 22 in a 1 1 mole ratio at 95 °C and 500 psig produced tetrahydro-2-methyl-l,3-oxazine (23) in 90% selectivity and 70% conversion of 22 by intramolecular cyclization of the hydroxy to the intermediate enamine. This synthesis is quite different from other syntheses (7) which involve Pd or Pt homogeneous complexes for the intramolecular hydroamination of ami-nopropyl vinyl ether to give 23. 

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