Bicyclic alcohols, formation

Formation of ring junctions with substrates containing an (Ej-alkene in a 5,6-relationship to the carbocation initiator leads to the thermodynamically more stable transfused rings, as exemplified by the cyclization of diene A to the trans-bicyclic product B. Interestingly, the same product B was obtained when the (Z)-isomer C was subjected to the same cyclization conditions. It appears that both dienes A and C cyclize initially to a common monocyclic intermediate E. Cyclization of E and trapping of the incipient cation by formic acid proceeds in a rrans-manner to give the bicyclic formate ester F, which is hydrolyzed under the reaction conditions to the alcohol B. ... 

Dehydrogenation of amino alcohols of type 40 affords even bicyclic compounds 41, the formation of which can be explained by nucleophilic attack of the hydroxyl group on the formed enamine salt (133,134). 

The reductive demercuration was marred by the loss of about half of the peroxide due to competing deoxymercuration which afforded 4-cycloocten-l-ol. An additional complication was the formation of a small amount of trans-1,2-epoxy-cw-cyclooct-5-ene. The bicyclic peroxide 50 was readily separated from the unsaturated alcohol by silica chromatography, but complete removal of the epoxide was more difficult. Preservation of the peroxide linkage was markedly higher in the bromodemercuration. The diastereoisomeric dibromoperoxides 51 were separated by HPLC, although only one isomer was fully characterised. 

As shown in Scheme 199, the 5-aminopyrimidine stmcture may be also incorporated into a more complex bicyclic system. Thus, diazotization of 3-amino-4-oxo-4//-pyrimido[ 1,23 lpyndazincs 1198 followed by treatment with 50% aqueous tetrafluoroboric acid results in precipitation of salts 1199. When heated with alcohols, nucleophilic attack on the carbonyl group opens the pyrimidine ring. The obtained species 1200 assume conformation 1201 that is more suitable for bond formation between the opposite charged nitrogen atoms. Alkyl l-(pyridazin-3-yl)-l//-l,2,3-triazole-4-carboxylates 1202 are obtained in 31-66% yield <2002ARK(viii)143>. 

A series of bicyclo[3.3.0]octanols are accessible by electroreductive tandem cyclization of linear allyl pentenyl ketones 189, as shown by Kariv-Miller et al. [189]. The electrolyses are carried out with an Hg-pool cathode and a Pt-flag anode. As electrolyte, tetrabutylammonium tetrafluororborate is used. The reaction is stereoselective, yielding only two isomers 192 and 193. In a competing reaction, a small amount of the monocyclic alcohol is formed. Since all the monocycles have the 1-allyl and the 2-methyl group in trans geometry it is assumed that this terminates the reaction. The formation of a bicyclic product requires that the first cyclization provides the cis radical anion which leads to cis-ring juncture [190] (Scheme 37). 

In another approach, 2-(alkylamino)alcohol is employed as starting material for aziridine syntheses with the aid of dihalogenophosphoranes (70BCJ1185). Intramolecular transformation of 3-azidopropyloxirane 73 results in a simultaneous formation of a condensed aziridino[l,2-a]pyrrol-idine system (Scheme 39). The azide group is first transformed into imino-phosphorane 74, the nucleophilic N atom cleaves the oxirane to form betaine 75 [as in the Mitsunobu reaction (81S1)], and the phosphorus is shifted from N to O and then eliminated as phosphane oxide under simultaneous cyclization to bicyclic 76 (89JA7500). 

Various aldehydes 184 and alcohols have been shown to be competent in the redox esterification of unsaturated aldehydes in the presence of the achiral mesityl triazo-lium pre-catalyst 186. Both aromatic and aliphatic enals participate in yields up to 99% (Table 13). Tri-substituted enals work well (entry 3), as do enals with additional olefins present in the substrate (entries 4 and 7). The nucleophile scope includes primary and secondary alcohols as well as phenols and allylic alcohols. Intramolecular esterification may also occur with the formation of a bicyclic lactone (entry 8). 

The chiral, nonracemic bicyclic lactams, used as starting materials for stereoselective alkylation reactions, are usually prepared by treating a mixture of the enantiomerically pure vicinal amino alcohol 1 with a 3-acylpropanoic or 4-acylbutanoic acid 2 (R4 = H) under acid catalysis in toluene with azeotropic removal of the resulting water1-17. When formation of the bicyclic aminal is complete, it is isolated as a diastereomeric mixture which is usually easy to purify and provides the major diastereomer 3. An alternative method for preparation of the bicyclic lactam uses the same conditions with a 2-substituted acid (R4 =1= H). This leads to a roughly 50 50 mixture of diastereomers 3 and 4 which can be used directly for the next step2,5,12. 

An extremely interesting extension of this method has led to the synthesis of monoethers of piperazinediones (88JOC5785), which are not otherwise easily accessible. The dichloroacetyl derivative (22) of the glycina-mide (21) undergoes base-catalyzed condensation with alcohols to give the piperazinediones (23). This has been used to generate bicyclic [n.2.2] piperazinediones in which the second ring is created by C—C bond formation. Thus, the butenediol derivative (24) obtained by the procedure out-... 

Cyclocondensation of 5-halovaleraldehydes (186) and 1,3-amino alcohols (187) gave equilibrium mixtures of tram- and c s-pyrido[2,l-h][l,3]oxazines (188 and 189), with a predominance of the frans-fused bicycle both diastere-omers contained the substituent in the equatorial position (90TL4281 94JA2617,94JOC6904). However, kinetic selectivity for the formation of cis-pyrido[2,l-h][l,3]oxazine (189) was exhibited versus the tram compound 188 in the case of the dimethyl derivative (R = R1 = Me) (90TL4281). 

In 1969 the reaction of 1,2,4,5-tetrazines (39) with imidates (198) was reported. The formation of the 1,2,4-triazine products (199) is explained by a [4 + 2] cycloaddition of the tetrazine with the C=N double bond of the imidate to give the bicyclic intermediate (200) which eliminates nitrogen and alcohol (69JHC497). Further studies on this reaction seem to... 

An important and frequently observed phenomenon in alkene pyrolysis is the ready equilibration of E and Z isomers at FVP temperatures above 500 °C. The apparently contrathermodynamic conversion of the E into the Z isomer has been quantified over the range 500-900 °C for stilbene, cinnamyl alcohol and cinnamonitrile37. In the last case, the proportion of Z isomer increases to 38% at 900 °C. In certain cases the diradical implicit in the isomerization process can be trapped by an intramolecular reaction and this is exemplified by the formation of 2-phenylindane in low yield from FVP of 56 at 700 °C37. The cis cyclobutene diester 58 is assumed to be formed as an intermediate in the FVP of the bicyclic sulphone 57 at 775 °C by loss of SO2 and ethylene. Under these conditions, however, it reacts further to give equal proportions of the E diesters 59... 

Reduction of cyclic and bicyclic ketones. This hydride reduces 4-r-butyl- and 3-methylcyclohexanone with some bias favoring formation of the more stable isomer. In contrast, 2-methylcyclohexanone is reduced preferentially to the less stable cis-isomer (72%). Essentially, only the ra-isomer is formed on reduction of 2-f-butylcyclohexanone (98% stereoselectivity). Norcamphor is reduced to the endo-alcohol in > 99% stereoselectivity, whereas the more hindered camphor is reduced to the exo-alcohol with 98% stereoselectivity. 

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