Cyclization with 1,2-Diol

Treatment of phenol with 1,2-diols and excess of cyclopentene (Sequiv.) in the presence of a well-defined cationic ruthenium hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1 mol%) in toluene at 100 C for 8-12h led to the formation of benzofuran derivatives (Eq. (7.18)) [24]. The catalytic C-H couphng method exhibited a broad substrate scope, tolerated carbonyl and amine functional groups, obviated the use of any expensive and often toxic metal oxidants, and liberated water as the only by-product. Furthermore, excellent regioselective addition of the linear 1,2-diols were observed, which yielded the -substituted benzofuran products exclusively. Such dehydrative C—H alkenylation and annulation reactions could be applied for a number of functionalized phenol and alcohol substrates of biological importance. 

Ruthenium-Catalyzed Heterocycle Synthesis via Intermolecular C-C/C-N Bond Formation Based on C-H Bond Activation 

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The same group also conducted a series of competition experiments with diols such as 36, which show that AgN03 and HgCl2 behave similarly in Scheme 15.8, the results for AgN03 are depicted [17]. It is obvious that a selective cyclization to a dihydropyran 37 is dependent on an alkyl chain such as R1 with R1 = H, for both R2 = H and R2 = alkyl an almost 1 1 mixture of 37 and tetrahydrofuran 38 was observed. The competition of a two-carbon chain with a four-carbon chain in 39 leads to a 2 1 mixture of the dihydropyran 40 as the major product and the tetrahydropyran 41 as the minor product. 

Both the (RR)- and (5S)-enantiomers of hydrobenzoin (Figure I4a) have been made to react (110, 117, 118) successfully in a (2 + 2) cyclization with ethylene glycol ditosylate in the presence of bases (e.g., NaOH in dioxane or NaH in MA -dimethylformamide) to give the enantiomeric tetiaphenyl-18-crown-6 derivatives (RRRR)-73 and (SSSS)-73. The corresponding optically pure tetra-anisyl, tetra-a-naphthyl, and tetra-/3-naphthyl-18-crown-6 derivatives 74, 75, and 76, respectively, have also been prepared in similar fashion (119). It should be noted that (RRRR)- and (,SSSS)-73 have also been obtained as a result of a base-promoted (1 + 1) cyclization (120) between the chiral extended diol and... 

The syntheses of (-l-)-mww,a ri,m -dicyclohexano-18-crown-6, i+)-trans-cyclohexano-15-crown-5, and (-l-)-r wis-cyclohexano-18-crown-6 (115) ftom (-l-)-mi/w-cyclohexane-l,2-diol (Figure 15) have been described. They involve base-promoted cyclizations with the appropriate ditosylates after chain extension of the chiral diol using the allylation-ozonolysis-reduction procedure. 

Simultaneous deprotection and cyclization of diols 60a and 60b with 3 M HCl in MeOH followed by acetylation yielded the 2,3-trans- ( 50%) (61a and 61b) and for the first time 2,3-cw-flavan-3-ol methylether acetate derivatives ( 20%) (62a and 62b) in excellent enantiomeric excesses (>99%). The optical purity was assessed by H NMR using [Eu(hfc)3] as chiral shift reagent. The absolute configuration of the derivatives of the tram- and cii-flavan-3-ol derivatives was assigned by comparison of CD data with those of authentic samples in the catechin or epicatechin series flavan-3-ols. Thus, the absolute configuration of the flavan-3-ol methyl ether acetates confirms the assigned configuration of the diols as derived from the Sharpless model. 

Similarly a diol 1 with given relative and absolute configuration may be monomesylated to give 2 and 4 which are cyclized with base to the epoxides 3 and 5. 

Considerably higher yields of [18]crown-6 were obtained when dichloride (32) was condensed with diol (31). Similar procedures for the synthesis of [12]crown-4 and [15]crown-5 have also been developed and the dichloride component can readily be replaced by its ditosylate derivative. Once again the presence of an alkali cation template can considerably increase the yield of the cyclization (77OS30). 

Cyclizations of chloral hemiacetal derivatives of cyclic allyl alcohols were regio- and stereo-selective (Table 6, entry 1), but a mixture of regioisomers was obtained from analogous derivatives of acyclic allyl alcohols with a nonterminal double bond.93 Hemiacetal derivatives of allyl alcohols with a terminal vinyl group have been cyclized with mercury(II) acetate to give acetal derivatives of threo 1,2-diols with moderate selectivities (equation 54 and Table 15, entries 1 and 2).147 Moderate to excellent stereoselectivity has been observed in the iodocyclizations of carbonate derivatives of allyl alcohols (entries 3-5).94a The currently available results do not provide a rationale for the variation in observed stereoselectivity. 

The C2-symmetric azetidines 34 can be synthesized from anti- 1,3-diols <2000EJ01815>. An enantioselective reduction of diketones 32 using [Ru/(7 )or(A)-BINAP] catalytic systems leads to the synthesis of 1,3-diols 33, which, after mesylation followed by cyclization with amines, afford azetidines 34 with ee higher than 95% (Scheme 27). 

The first synthesis of (R)-4,5-dihydro-37/-dinaphtho[2,l-f l, 2 -i ]selenepin oxide 110 has been achieved from (R)-(+)-l,l -bi-2-naphthol, which in turn was obtained by resolution of raol,l -bi-2-naphthol. Palladium-catalyzed alkoxy carbonylation of the alcohol 108 gave a dimethyl ester which was then reduced by LiAlfLi, and the resultant diol converted to key intermediate chloride 109. Cyclization with sodium selenide gave a novel enantiomerically pure selenide, which upon oxidation yielded the desired selenoxide 110 <2000SC2975>. 

The Kolbe reaction of 3-hydroxy-2-(trifluoromethyl)propanoic acid (9) affords the isomerized diols 10 in 95% yield, which are cyclized with phosphoric acid to form the 3,4-bis(tri-fluoromethyl)tetrahydrofurans 11. The electrolysis has been carried out under a constant current (2.0 A) at 5 C using a beaker-type undivided cell attached with platinum electrodes (40 cm X 40 mm). 

The thermal rearrangement of O-allyl trichloroacetimidates 1 affords the corresponding 7V-allyl amides 31 2, which have been cyclized with the aim of obtaining amino diols or amino alcohols different to those from the cyclization of the trichloroacetimidates. Cyclization of these latter substrates 1 leads to 4,5-dihydro-4-(l-iodoalkyl)oxazoles 2, while treatment of unsaturated trichloroacetamides 3 with /V-iodosuccinimide3 in chloroform affords the corresponding 4,5-dihydro-5-(l-iodoalkyl)oxazoles 4 in high yield. These heterocyclic products are protected forms of the corresponding amino alcohols. 

A 2- or 6-hydroxy-substituted purine can be prepared from the corresponding 4,5-diamino-pyrimidinol by cyclization with an acid, ester, ortho ester, or amide. If the ring closure is performed with reagents such as urea, alkyl chloroformates, urethanes, phosgene, and alkyl isocyanates, the 8-hydroxypurines are formed. Various xanthine and uric acid derivatives have been prepared by the condensation of 5,6-diaminopyrimidine-2,4-diols with formic acid. Purin-2-ol (1) was prepared by this route from 4,5-diaminopyrimidin-2-ol and ethyl orthoformate. ... 

However, this method fails for 1,2-diols like (79) or (81), from which the epoxides (80) and (82) are generated (equations 28 and 29). This involves an SN2-type cyclization with retention at the secondary... 

The authors opted to install the bromotetrahydropyran A-ring last due to its possible instability under radical, strongly basic, and/or acidic conditions. The D-ring was envisioned to arise from a stereoselective epoxidation followed by cyclization to afford the tetrahydrofuran framework. Key to achieving this plan was accessibility to structure 56 (Scheme 10). This fragment in turn was envisioned to be assembled by coupling the anion derived from 57 with epoxide 58. Compound 58 could presumably be accessed via stereoselective cyclizations from diol 59. 

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