Allyl alcohols 2- substituted

In spite of these complications, the allylic alcohol substitution reaction provides a simple method for preparing a variety of carbonyl compounds and alcohols often not readily accessible by other methods. Some examples of the reaction are shown in Table IX. 

The allylic alcohol substitution reaction may also be carried out in DMF solution with sodium bicarbonate as the base at 100 to 125° with palladium-phosphine catalysts, in which case only carbonyl products are formed. With this catalyst combination nonallylic, unsaturated alcohols also react to form carbonyl compounds in good yields. For example, in an extreme case, 9-decen-l-ol and bromobenzene gave some 10-phenyldecanal (40) ... 

Allylsilanes. A general synthesis of allylsilanes involves alkylation at the imposition of an allylic alcohol substituted at the 7-position by a trimethylsilyl group or at the a-position by a trimethylsilylmethyl group with an organolithium compound mediated by this phosphonium iodide (l).2... 

Diastereoselective epoxidation of an allylic alcohol. Epoxidation of either a cis-or Irons-allylic alcohol substituted in the y-position by an alkoxy function by either m-ehloroperbenzoic acid or r-butyl hydroperoxide/VO(acac), results mainly in the anti-cpoxide (9, 109). Epoxidation of the allylic alcohol 1 with m-chloroperbenzoic acid conforms to this pattern, but epoxidation with f-butylhydroperoxide and VO(acac)2 mediated by titanium (IV) isopropoxide favors formation of the jyn-epoxide by a (actor of 10 1. The methyl group attached to the double bond is necessary for this unusual syn-selectivity when it is lacking, epoxidation with f-butyl hydroperoxide/ Ti(l V) is anti-sclcctivc, but less so than epoxidation with the peracid.1... 

Heteroconjugate addition (9. 311). The diastcrcoselcctive conjugate addition of methyllithium to a secondary allylic alcohol substituted with a SO,C,H, and a Si(CH,)< group to give the. yvn-adduct as the only or major product (equation I) has been extended to other alkyllithiums and used to prepare sytt and u/(//-diastercomcrs with different... 

Cyclopropanation of vinylorganometallic compounds. Molandcr cyclopropana-tion of allylic alcohols substituted by silyl or stannyl groups can show high diastereo-sclcctivity particularly when carried out with a large excess of the samarium reagent. 

Cyclopropanation of allylic alcohols substituted by a tin group gives a single diastereomer in good yield. These tin-substituted cyclopropancs can undergo trans-metalation (CH3Li, THF, 0°). 

Cyclopropanation of vinylorganomH tion of allylic alcohols substituted by sily selectivity particularly when carried out 1... 

The diastereoselectivity of the epoxidation of allylic alcohols substituted by polypropionate units is highly dependant upon the nature of the protecting group and on the stereochemistry of the stereogenic centers (eqs 37 and 38). ... 

Substituted epoxides are attacked by organocopper reagents at the least hindered carbon atom and form alcohols (C.R. Johnson, 1973A). With a, 9-unsaturated epoxides tram-allylic alcohols are produced selectively by 1,4-addltion (W. Carruthers, 1973 G.H. Posner, 1972). 

Aryl and vinylic bromides and iodides react with the least substituted and most electrophilic carbon atoms of activated olefins, e.g., styrenes, allylic alcohols, a,p-unsaturated esters and nitriles. 

A) Sn2 substitution at the allylic alcohol with hydrobromic acid followed by reaction with the requisite secondary amine, or... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

Substituted allylic alcohols are carbonylated using the o.vidizing system of PdCl2 and CuCU in the presence of HCl and oxygen at room temperature and 1 atm of CO to give the 7-lactone 16 in moderate ylelds[20]. Carbonylation of secondary and tertiary allylic alcohols catalyzed by Pd2(dba)j and dppb affords the 7-lactone 17 by selective attack of CO at the terminal carbon under fairly severe conditionsf21]. 

Fonnation of allylic products is characteristic of solvolytic reactions of other cyclopropyl halides and sulfonates. Similarly, diazotization of cyclopropylamine in aqueous solution gives allyl alcohol. The ring opening of a cyclopropyl cation is an electrocyclic process of the 4 + 2 type, where n equals zero. It should therefore be a disrotatory process. There is another facet to the stereochemistry in substituted cyclopropyl systems. Note that for a cri-2,3-dimethylcyclopropyl cation, for example, two different disrotatory modes are possible, leading to conformationally distinct allyl cations ... 

A synthetically valuable reaction sequence is the chlorodifluoroacetylation of various substituted allylic alcohols and the subsequent Reformatskii-Claisen rearrangement of the ester thus formed to interesting 2,2-difluoropentenoic acid derivatives [25] (equation H) Comparable sequences have been reported for ally monofluoroacetates [26] and allyl 3,3,3-trifiuoropropanoates [27] (equations 15 and 16). 

In 1980, Katsuki and Sharpless communicated that the epoxidation of a variety of allylic alcohols was achieved in exceptionally high enantioselectivity with a catalyst derived from titanium(IV) isopropoxide and chiral diethyl tartrate. This seminal contribution described an asymmetric catalytic system that not only provided the product epoxide in remarkable enantioselectivity, but showed the immediate generality of the reaction by examining 5 of the 8 possible substitution patterns of allylic alcohols all of which were epoxidized in >90% ee. Shortly thereafter. Sharpless and others began to illustrate the... 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

In general, 2-substituted allylic alcohols are epoxidized in good enantioselectivity. Like glycidol, however, the product epoxides are susceptible to ring opening via nucleophilic attack at the C-3 position. Results of the AE reaction on 2-methyl-2-propene-l-ol followed by derivatization of the resulting epoxy alcohol are shown in Table 1.6.1. Other examples are shown below. 

This class of substrate is the only real problematic substrate for the AE reaction. The enantioseleetivity of the AE reaction with this class of substrate is often variable. In addition, rates of the catalytic reactions are often sluggish, thus requiring stoichiometric loadings of Ti/tartrate. Some representative product epoxides from AE reaction of 3Z-substituted allyl alcohols are shown below. 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

There are only limited examples of AE reactions on 2,3Z-substituted allyl alcohols. This may be due in part to the difficulty involved in selectively preparing the starting allylic alcohol. 

Although the limited examples of AE reactions on 2,3Z-substituted allyl alcohols appear to give product epoxides in good enantioselectivity, the highly substituted nature of these olefins can have a deleterious effect on the reactivity. For example, Aiai has shown that the 2,3E-substituted allyl alcohol 30 can be epoxidized with either (-)-DET or (+)-DET in good yields and enantioselectivity. However, the configurational isomer 32 is completely unreactive using (-)-DET, even after a 34 h reaction time. 

The first, and so far only, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides with alkenes was reported by Ukaji et al. [76, 77]. Upon treatment of allyl alcohol 45 with diethylzinc and (l ,J )-diisopropyltartrate, followed by the addition of diethylzinc and substituted hydroximoyl chlorides 46, the isoxazolidines 47 are formed with impressive enantioselectivities of up to 96% ee (Scheme 6.33) [76]. 

Denniatk and co-wotkets teporied tlie brst example in 1990 [16], using substrates 1, s7ntliesized Grom adiital allylic alcohols and tead dy ava dable optically active amine auxdiaries. Substrates 1 were tlien employed in coppet-niediaied allylic substitution reactions, as shown in Sdienie 8.4. 

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

Table 6.2 Examples of epoxides generated by AE, applied to different primary allylic alcohols showing all eight basic substitution patterns.

The AE reaction catalyzed by titanium tartrate 1 and with alkyl hydroperoxide as terminal oxidant has been applied to a large variety of primary allylic alcohols containing all eight basic substitution patterns. A few examples are presented in Table 6.2. 

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