4- Alkenols

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-alkylated alkyl iodides 931. Q.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779-781]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl aicohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783]. 

Tetrahydropyran- and tetrahydrofuran-substituted rings are common in many complex natural products, such as polyether antibiotics, displaying a wide range of biological properties [4]. An appropriate combination of OH-directed diastereose-lective epoxidation of y- and 8-alkenols [VO(acac)2/TBHP or MCPBA] [5] or ster-... 

For the formation of substituted THF rings (Route a, Scheme 8.1), Kishi developed a procedure based on the hydroxy-directed epoxidation of a y-alkenol [10]. Epoxidation of bishomoallylic alcohol 3 by TBHP/VO(acac)2 by this approach, followed by treatment of the intermediate epoxide 4 with acetic acid, gave the TH F derivative 5 of isolasalocid A (a 5-exo cydization Scheme 8.2) [11]. Further epoxidation of 5 (a y-alkenol) under the same conditions, followed by acetylation, afforded epoxide 6. For the synthesis of the natural product, the configuration of epoxide 6 had to be inverted before the second cydization reaction. Epoxide 6 was consequently hydrolyzed under acid conditions to the corresponding diol and was then selectively... 

The structure of glabrescol was subsequently revised, and the new structure was synthesized enantioselectively through sequential hydroxy-directed anti-oxidative cyclization of acyclic y-alkenols with VO(acac)2/TBHP to construct the adjacent THF rings via epoxides under acid conditions [35b],... 

Cp2Zr(H)(Cl) (8). The apparent record for catalyzed double bond movement is on 9-decene-l-ol to decanal (nine positions) using Fe3(CO)i2 (9). However, 30 mol % was required, which means that nearly a mole of metal was used per mole of alkenol. Herein we expand upon our initial report (10) of a very active catalyst (1) which has been shown to move a double bond over 30 positions. Catalyst 1 appears to have an intriguing and useful mode of action, in which the pendant base ligand performs proton transfer on coordinated alkene and Ti-allyl intermediates in a stereoselective fashion. 

The addition of carbon-based radicals to alkenes has been shown to be successful in water. Thus, radical addition of 2-iodoalkanamide or 2-iodoalkanoic acid to alkenols using a water-soluble radical initiator in water generated y-lactones (Eq. 3.29).118... 

A convenient procedure for the lactonization of alkenols has been recently revealed by Borhan and coworkers [19]. This methodology was successfully applied in the total synthesis of (+)-tanikolide (7-37), a natural product of marine origin which exhibits antifungal activities. Thus, when alkenol 7-36 is subjected to soluble oxone and a catalytic amount of 0s04, a smooth domino oxidative cleavage/lactonization process takes place which leads, after debenzylation, to the desired product in good overall yield (Scheme 7.12). 

Name compounds containing a double bond and an alcohol group as alkenols (or cycloalkenols) and give the alcohol carbon the lower number. 

The vanadium-catalyzed epoxidation of hindered homoallylic alcohols has been described by Prieto and coworkers [339]. Reaction times for the epoxidation in a series of cis- and trans-2-methyl-alkenols were significantly reduced from 6-10 days to... 

When Wacker-type reactions are performed under a CO atmosphere, the (3-H elimination pathway can be suppressed in favor of CO insertion and subsequent nucleophilic cleavage of the acyl metal species.399 This alkoxycarbonylation process has found widespread utility, particularly in the synthesis of five- and six-membered oxacyclic natural products. For example, the THF core of tetronomycin was prepared by the Pd-catalyzed alkoxycarbonylation of 4-alkenol derivatives (Equations (117) and (118)), where stereocontrol was achieved by utilizing either the directing ability of a free hydroxyl or the conformational bias imposed by a bulky silyl ether.420 Additional examples making... 

The cyclization of alkenols can also occur through an interesting relay mechanism (Equation (125)). Under AuC13 catalysis, the alkyne of an enynol is first activated to promote a cationic G-G bond-forming cyclization with the alkene. The G-O bond-forming ring closure then occurs via capture of the carbocation by the alcohol.451... 

In addition to /3-H elimination, olefin insertion, and protonolysis, the cr-metal intermediate has also proved to be capable of undergoing a reductive elimination to bring about an alkylative alkoxylation. Under Pd catalysis, the reaction of 4-alkenols with aryl halides affords aryl-substituted THF rings instead of the aryl ethers that would be produced by a simple cross-coupling mechanism (Equation (126)).452 It has been suggested that G-O bond formation occurs in this case by yy/z-insertion of a coordinated alcohol rather than anti-attack onto a 7r-alkene complex.453... 

The results indicate that 3-butenols and longer cj-alkenols can be alkylaluminated with a variety of alkyldiiso-butylalanes 128 to produce, after hydrolysis, the corresponding methyl-substituted alkanols 130 in good yields and with 90-93% ee. 

It has recently been shown that some of the sluggish reactions, such as those with styrene and w-alkenol derivatives, can be significantly accelerated by the addition of H20, MAO (methylaluminoxane) [167], and IBAO (isobutylaluminoxane) [168], and that the ee values can be improved by several % (Generalization 17). Some of the earlier results discussed above have also been reviewed recently [169,170]. 

Studies of the transfer of Br+ and I+ from amine-coordinated halonium ions to acceptor l-co-alkenols have been undertaken to determine the mechanism in an effort to assist in the development of chiral transfer reagents. Transfer of Br+ and I+ from two commercially available dimeric hydroquinine and hydroquinidine ligands ((DHQ)2PHAL and (DHQD)2PHAL) to various 1, (o-alkenols and l,co-alkenoic acids is shown to provide enantiomeric excesses of 4-47% depending on the acceptor alkene. 

Figure 1. Generalized scheme for halocyclization of a 1, oo-alkenol or l,co-alkenoic acid, R=0, H2, n=l-3.

In Case 1 both the ring closure steps (with rate constants ks and kR) are faster than dissociation of the 7r-complexes to reform the alkenol and N-X+ species. Here the [S]/R] product ratio is determined only by the difference in the activation energy leading to the 7is- and rcR-complexes because immediately after these are formed the cyclization occurs. Thus, the chirality is set by the approach of the alkene to the halonium ion. 

Figure 6. Reaction coordinate diagram for Case 2 of the reaction of the monoamine-X ion with alkenol through ns and KR-complexes forming S, and R...

Chiral induction for the reaction of chiral quinuclidine-X+ with l,co-alkenols... 

Table 3. Enantiomeric excesses obtained from halocyclizations of various l,o-alkenols or l,co-alkenoic acids with halonium ions of dimeric hydroquinidine or dimeric hydroquinine species 14,15,16. ... 

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