Allenyl alcohols

The 2-(l-alkynyl)oxirane 78 reacts with an organozinc reagent yielding the /9-allenylic alcohol 79[35]. 

The Pd-catalysed carbonylation of alkynyl epoxides 60 and alkynyldioxolanones 61 leads to the allenes 62 which can then be converted to the same pyranones through a tandem conjugate addition-cyclisation (Scheme 40) <00JCS(P1)3188>. Carbonylation of allenyl alcohols is catalysed by Ru3(CO)i2 and yields 5,6-dihydropyran-2-ones . 

Reaction of a-allenyl alcohol 147 with methanesulfonyl chloride and triethylamine in toluene at 190 °C, in a sealed tube, led to the tricyclic dihydropyrrolizin-4-one 149 in 35% yield. This transformation involves a domino mesylation/ intramolecular Diels-Alder cycloaddition via diene 148 (Scheme 29) <2002CC1472>. 

Another interesting cyclization employing 2-hydroxy-substituted methoxyallenes 101 was reported by Takahashi et al. (Scheme 8.29) [85]. Their novel Ru3(CO)12-cata-lyzed carbonylation reaction of allenyl alcohols 101 furnished y-lactones 108 in almost quantitative yields. 

Allenyl alcohols have been used as starting materials for a different kind of dihydrofuran synthesis. This is a process with great generality and utility in total synthesis. An example of the process is shown in Eq. 13.43 [42]. Treatment of allenyl alcohol 133 with silver nitrate in aqueous acetone at room temperature leads stereospe-cifically to dihydrofuran 134 in excellent yield. A similar reaction occurs with allenyl ketones, leading to furans. The isomerization is known to take place with Rh(I) [43], Ag(I) [44, 45] Pd(II) [46], Au(III) [47, 48] Cu(I) [49] or Hg(II) [50, 51],... 

The oxidative cyclization of allenyl alcohol 135 with a small excess of dimethyl-dioxirane leads to an intermediate diepoxide that rearranges to hydroxyfuranone 136 in 55% yield (Eq. 13.44) [52]. If the oxidative cyclization is conducted in the presence of 0.5 equiv. of toluenesulfonic acid, the major product is the furanone lacking the a-hydroxy group of 136. Hydroxyfuranones or pyranones are available from the same kinds of reactions of 5-methylhexa-3,4-dien-l-ol. 

Ru3(CO)12 catalyzes the carbonylation of the sp carbon of allenyl alcohols, giving rise to y- and <5-lactones in good yields (Scheme 16.30) [34], The methodology was successfully applied to the syntheis of seven- and eight-membered lactones (Scheme 16.31) [35],... 

Scheme 16.96 Cross-coupling reaction of an a-allenyl alcohol and phenylacetylene.

Allenyl alcohols 10 react with lithium bromide in the presence of a palladium(II) catalyst to afford tetrahydrofurans and tetrahydropyrans 11 in good yield (Scheme 17.6) [7]. The mechanism of the reaction is similar to that discussed in Sect 17.2.1. i.e. it proceeds via a 2-bromo(jt-allyl)palladium(II) complex. In this case, however, the second nucleophile is not bromide ion but the alcohol moiety. As stoichiometric oxidant p-benzoquinonc (BQ) or copper(II) together with oxygen can be used. 

In analogy with the oxybromination reaction of allenyl alcohols, allenyl acids 12 afforded five- and six-membered lactones 13 on treatment with lithium bromide in the presence of palladium acetate (Scheme 17.8) [7, 8],... 

In situ epoxidation of allenyl alcohols [20], aldehydes [21], acids [22] and sulfonamides [23] followed by intramolecular ring opening of the intermediates was thoroughly investigated by Crandall and co-workers. They showed that products formed either from the allene oxide or the spirodioxide intermediate can be prepared selectively. Allenyl acids 56, for example, react first with DMDO on their more substituted double bond. When the concentration of the oxidant is low (DMDO is formed... 

The corresponding reactions of allenyl alcohols proceed mostly via the spirodioxide intermediate (Scheme 17.21) [20], Whereas a-allenyl alcohol 61 gives the corresponding tetrahydrofuranone 62 in only moderate yield, /l-allenyl alcohols 63 react much cleaner to afford tetrahydropyranones 64 in good yield. In the case of y- and d-allenyl alcohols 65 the spirodioxide intermediate is attacked intramolecularly on the carbon atom closer to the alcohol moiety, so that tetrahydrofurans and tetrahy-dropyrans 66 are formed. 

When allenyl aldehydes are allowed to react with DMDO, the aldehyde moiety is not oxidized to the acid except for monosubstituted allenes [21]. In all other cases, the carbonyl oxygen participates as a nucleophile in the opening of the intermediate epoxide. From 2,2,5-trimethy]-3,4-hexadienal 67, for example, five different products can be synthesized selectively under different reaction conditions (Scheme 17.22). When p-toluenesulfonic acid (TsOH) is present or DMDO is formed in situ, then the initially formed allene (mono)oxide reacts with the aldehyde moiety to give 68 or 69. In the presence of excess DMDO and the absence of acid, three other products (70-72) can be formed via the spirodioxide intermediate. These reactions, however, seem to be less general compared with similar reactions of allenyl acids and allenyl alcohols. y-Allenylaldehydes 73 can be cyclized to five-membered hemiacetals 74 via the spirodioxide intermediate. 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

In a different study, a d-allenyl alcohol 81 containing a chiral substituent was oxidized by DMDO and then cyclized to afford the substituted tetrahydropyran 82 with good diastereoselectivity [19] (Scheme 17.24). Interestingly, when oxone was used instead of DMDO, the eight-membered cyclic ether 83 was formed via the allene oxide intermediate. 

Norpseudoephedrine-derived amino ether 81 was also used as a chiral coordinating agent for the enantioselective [2,3]-Wittig rearrangement. The rearrangement of propargyl ether 82 induced by n-BuLi/81 provided allenyl alcohol (5 )-83 in 62% ee (equation 45). In contrast, a similar reaction with (-)-24 provided only 9% ee of (S)-S3. 

Comparable lactones 19 can be synthesized from allenyl alcohols 18 by a ruthenium-catalyzed carbonylative cyclization [19] and an extension of this procedure to the synthesis of lactames 21 has also been reported [20]. 

A ruthenium-promoted carbonylation of allenyl alcohols 884 is a powerful method for the synthesis of 5,6-dihydropyran-2-ones 885 (Equation 356) <20000L441, 2003JOC8571>. Co2(CO)6-mediated tandem [5+1]/ [2+2+1] cycloaddition reactions of the epoxide 886 with carbon monoxide provide a one-pot synthesis of tricyclic 5,6-dihydropyran-2-ones 887 in good yield (Equation 357) <2003JA9610>. 

Following preliminary observations on allenyl alcohols from Gore27-31 and Balme32 along with Claesson and Olsnon,33 Marshall et al. demonstrated in a seminal publication34 that allenyl ketones (R3 = alkyl, Scheme 5.2) or allenyl aldehydes... 

Because unsaturated lactones and lactams are of importance as biologically active compounds, the carbonylative cyclization of alkynyl alcohols, alkynyl amines, and their allenyl derivatives has been extensively studied using various transition-metal complexes. Takahashi et al. [35] reported that Ru3(CO)12 also catalyzes the cyclocarbonylation of allenyl alcohols to five- to eight-membered unsaturated lactones (Eq. 20). 

Substituted 2(5ff)-furanones were also synthesized from allenyl alcohols 36 (Eq. 18) [28]. In the presence of 1 mol % of Ru3(CO)12, Et3N and 10 atm CO, 36 underwent cyclocarbonylation to afford the butenolides 37 in excellent yields. Remarkably, the ruthenium(0)-catalyzed cyclocarbonylation protocol is applicable to the syntheses of 6-8-membered a,/ -unsaturated lactones 38-40 in good yields (Eq. 19) [28,29]. 

Indium-mediated propargylation of 4-oxoazetidine-2-carboxaldehydes gives the homopropargyl alcohol 3 and the allenyl alcohol 4 with moderate selectivities. In the case involving propargyl bromides bearing an aliphatic or aromatic substituent at the terminal position, //-allenyl alcohols 5 are selectively formed over yy/z-alcohols 6 (Scheme 10).114... 

Yu, X.H., Seo, S.Y., and Marks, T.J. (2007) Effective, selective hydroalkoxylation/cyclization of alkynyl and allenyl alcohols mediated by lanthanide catalysts. Journal of the American Chemical Society, 129, 7244. 

A serendipitous discovery by Tius has been developed into a useful a-methylenecyclopentene annu-lation procedure. In an attempted synthesis of orthoquinones. Tins treated the allenyl alcohols (71), derived from addition of 1-lithio-l-me xyallene to a-silyloxymethylene ketones, with BF3-Et2. The product a-methylenecyclopentenones (72) were obtained in good yield (equation 39). The process can be... 

The intermolecular coupling of allenes 123 and enones 124 selectively afforded dienones 125 in 53-81% yields (Scheme 4.45) [93]. As a catalyst precursor, [CpRuCl(cod)] was employed with CeCl3 7H20 and an alkynol 126 as activators. The proposed reaction mechanism involves the regioselective oxidative cyclization of the two components on a cationic ruthenium center, leading to the ruthenacyclopentane intermediate 127. When allenyl alcohols 128 were employed under otherwise identical conditions, the final products were cyclic ethers 129 (Scheme 4.46) [94]. As a catalyst precursor, the cationic ruthenium complex 68 can be used in the absence of the alkynol 126. The ether ring was considered to be formed directly via the ruthenacyclopentane 130 or alternatively through its Jt-allyl form 131. 

The anomalous hydride reduction of hexamethyl-Dewar benzene oxirane has been reported. With AIH3, a-allene substituted oxiranes give a- and / -allenyl alcohols. ... 

Various metal acetylides are used for smooth coupling with propargylic halides, acetates, and 2-(l-alkynyl)oxiranes to give 2,3-alkadien-5-yn-l-ols [35,41]. As a synthetic application, unstable 2,3-octadiene-5,7-diyn-l-ol (171), a fungus metabolite, has been synthesized by the coupling of 4-(trimethylsilyl)butadiynylzinc chloride (168) with 2-ethynyloxirane (169) to give the allenyl alcohol 170, followed by desilylation (Scheme 11-46) [41]. 

Alkynylepoxides [123,142,143 Eq. (68) 142] and alkynyl propiolactones [Eq. (69) 144] afforded allenyl-alcohols or allenyl-carboxylic acids. Diastereoselective ring opening of alkynylepoxides has been studied [143,145]. The use of optically active propargyl substrates enables the synthesis of optically active allenes [Eq. (70) 146] [10,140,145-147]. A subtle change of the reaction medium may drastically change the degree of chirality transfer, which has been systematically examined [145]. 

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