Alcohols intramolecular addition

In addition. Barton s group Isolated two compounds which may be viewed as products of Intramolecular alcohol addition. These toxlsterols were assigned structures 9 and 10. The stereostructure of 9 was confirmed by X-ray analysis of a derivative (91b). Both toxlsterols show a three-top UV-absorptlon spectrum with maxima at 243, 252, and 262 nm. 

An interesting approach to zr n.v-2,3-disubstituted cyeloalkanones is offered by auxiliary controlled intramolecular Michael additions. The diastereoselectivity depends on the chiral alcohol used193> l94. When the borneol derivative 7 was used as substrate, a single diastereomer of 8 resulted when the reaction was performed at 25 "C under thermodynamic control with a catalytic amount of sodium hydride in benzene. 

The reaction of 2-aminobenzyl alcohol 376 with 2-chloro-4,5-dihydroimidazole afforded [2-(4,5-dihydro-177-imidazol-2-ylideneamino)phenyl]methanol hydrochloride 377, which upon treatment with carbon disulfide gave l-(477-3,l-benzoxazin-2-yl)imidazolidine-2-thione 378 (Scheme 71). The assumed reaction mechanism involved the initial formation of the dithiocarbamate 379, which underwent intramolecular nucleophilic addition to furnish the unstable thiazetidine 380. By nucleophilic attack of the hydroxy group on the carbon atom of the thiazetidine ring, thiocarbamate derivative 381 was formed, which gave the final 3,1-benzoxazine 378 by an intramolecular cyclocondensation with the evolution of H2S <2006H(68)687>. 

Alcohol addition was also studied by Hashmi et al. in intramolecular processes [28]. Through gold catalyzed cyclizations of (Z)-3-ethynylallyl alcohols 157, these authors were able to obtain furans 159. Reaction occurred via intermediate 158, which tautomerized the heteroaromatic furan, which is thermodynamically more stable (Scheme 8.15). 

Sometimes, enones arising from the oxidation of allylic alcohols with active Mn02 suffer intramolecular conjugated addition from amines (see page 303), or alcohols properly75 positioned inside the same molecule. 

Simple allenes (209) react with dimethyldioxirane (200) to give the corresponding spiro-dioxides 210 in instances where diastereoisomeric spiro-dioxides are possible, there is usually an acceptable stereochemical preference for epoxidation to occur anti to the alkyl substituents324,325. Allenic alcohol 211 yields the highly functionalized tetrahydro-furan 212 and tetrahydropyran derivatives by intramolecular nucleophilic addition of the hydroxy group to an intermediate allene diepoxide324. 

I.actone annelation. A new lactone synthesis from an allylic alcohol such as 1 involves a Cluiscn rearrangement (4, 234 235) followed by an intramolecular Michael addition, as formulated in equation (I). 

Monocyclic Phosphoranide Anion. The intramolecular oxidative addition of hydroxyalkyl phosphites, which gives P-H phosphoranes, is well known (10). Some P-H phosphoranes are so stable that the open-chain P(III) tautomers cannot be detected spectroscopically or even by attempted H2O2 oxidation (8). Thus, it is surprising to find no evidence for an equilibrium between phosphine alcohol 1 and its closed-ring tautomer phosphorane 2. Phosphine 1 is quaternized by alkyl halides giving phosphonium halides such as 3. These in turn are converted to alkoxyphosphor-anes, such as 4 by NaH (Scheme I). 

Dialkylaminomethyl alkyl (and aryl) sulfides result from the treatment of a-halogeno-amines with mercaptans (thiophenols).325 Dehydrogenation of amino-alcohols with mercuric acetate182,328 is accompanied by the intramolecular nucleophilic addition of the alkoxyl group when formation of a five- or six-membered ring is possible, e.g. ... 

Oxidative addition of the silane to the metal is fast and reversible 30 therefore unless the pentacoordinated silane drastically slows down the oxidative addition process, pentacoordination will not alter the rate of the reaction at this stage of the cycle. The increased reactivity of le may be explained by the attack of the alcohol on the pentacoordinated silane that would form after oxidative addition (Figure 9A). The rate of the alcohol addition is increased by the higher reactivity of the pentacoordinated silicon center. This may explain the slower reactivity for those alkoxysilanes that cannot form this intramolecular coordination complex due to the absence of a nearby Lewis basic atom. We had observed during the comparison of aliphatic alcohol to benzyl alcohol that the nucleophilicity of the alcohols has an effect on the rate of the reaction. This is evidence that the alcohol and the silane are involved in the rate-determining step with 10 % Pd/C catalytic system. 

Homopropargylic alcohols (but-3-ynols) as well as propargylic epoxides are suitable products to form cyclic ruthenium alcoxycarbenes upon intramolecular nucleophilic addition of the OH group to the electrophilic a-carbon of ruthenium vinylidene species. The recovery of the organic ligand as a lactone... 

The selective intramolecular nucleophilic addition of a hydroxy group at Cyof a ruthenium allenylidene generated by activation of propargylic alcohol by RuCl(Cp)(PPh3)2/NH4PF6 provides a ruthenium vinylidene species, which reacts with allylic alcohols as previously described in the section Formation of Unsaturated Ketones (Eq. 11, Scheme 18) [79]. This unprecedented tandem reaction makes possible the construction of tetrahydrofuran derivatives in good yields and has been used as a key step in the synthesis of (-)calyculin A [80]. 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

A stereoselective intramolecular Michael addition of semiacetals to a,/j-unsaturated esters and amides has been utilized in order to prepare syw-l,3-diols. Thus, the alcohol 1 reacts with benzaldehyde in the presence of potassium fer/-butoxide in tetrahydrofuran at 0 °C to give the corresponding benzylidene acetals 2 in good yield and very high diastereoselectivity155. 

A final class of oxy-Cope rearrangements leading to cyclodecenones is represented by spirodienol (120), which rearranges to a bicyclic ketone (121) containing a bridgehead double bond. ITie related alkynic alcohols (122) behave similarly, but when R is H the initial product imdergoes an intramolecular Michael addition to afford (123). 

Homopropargylic alcohols as well as propargylic epoxides and pentynols readily form cyclic ruthenium alkoxycarbenes upon intramolecular nucleophilic addition of the OH group to the electrophilic a-carbon of ruthenium-vinylidene species. Their oxidation in the presence of N-hydroxysuccinimide leads to the formation of penta-lactones. The best catalytic system reported until now for this transformation of but-3-ynols is based on RuCl(C5H5)(cod), tris(2-furyl)phosphine, NaHCOs as a base, in the presence of nBu4NBr or nBu4NPp6, and N-hydroxysuccinimide as the oxidant in DMF-water at 95 °C (Scheme 8.11) [22]. 

In the lactone acylations discussed above, there was never any evidence for a competing side reaction due to break down of the hemiketal moiety and Michael addition of the alcohol to the newly formed pro-pargylic ketone. This may be taken as filler evidence for the stability of the ketal-alkoxide intermediate however, hemiketal ring opening and intramolecular Michael addition would provide an... 

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