Reactions with allenic alcohols

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

In additions to alkynols, both possible orientations are noted. The balance between them is sensitive to steric effects bulky substituents at or near one carbon of the triple bond tend to favor carbon—carbon bond formation at the other carbon. In reactions with propargylic alcohols anti-addition products are seen that result from carbon—carbon bond formation at the triple-bond carbon nearer the OH group. These are often accompanied by allenes, the result of addition of the opposite orientation followed by elimination ... 

Reductive carbonylation of readily available alkynols in the presence of cationic hydride complex of palladium and water yields dienoic acids (Scheme 81). A similar reaction has been achieved with allenic alcohols. ... 

The reaction of phenylselenyl chloride with allenic alcohols is general and stereochemically clean as shown by the conversion of (61) (62). Extensions... 

The dimerization of allenic compounds led to linear or cyclic couplings. The [CpRu(CH3CN)3]PF6-catalyzed reaction of allenic alcohols with acetic acid in the presence of Cu(OAc)2 afforded the corresponding linear dimers with addition of acetate group [111] [Eq. (49)]. An acetoxyruthenacycle formed from an internal and a terminal double bond is proposed as intermediate. 

However, the reaction with aldehydes and ketones affords, along with allenic alcohols, their N-ethynyl isomers, the content of which in the products mixture can reach 60% (in the case of the reaction with paraform) (Scheme 2.224). The mixture composition is defined to a large extent by the reaction conditions and the electrophile nature. 

To a mixture of 100 ml of THF and 0.10 mol of the epoxide (note 1) was added 0.5 g Of copper(I) bromide. A solution of phenylmagnesium bromide (prepared from 0.18 mol of bromobenzene, see Chapter II, Exp. 5) in 130 ml of THF was added drop-wise in 20 min at 20-30°C. After an additional 30 min the black reaction mixture was hydrolysed with a solution of 2 g of NaCN or KCN and 20 g of ammonium chloride in 150 ml of water. The aqueous layer was extracted three times with diethyl ether. The combined organic solutions were washed with water and dried over magnesium sulfate. The residue obtained after concentration of the solution in a water-pump vacuum was distilled through a short column, giving the allenic alcohol, b.p. 100°C/0.2 mmHg, n. 1.5705, in 75% yield. 

Apparatus. 500-ml round-bottomed, three-necked flask with a gas inlet tube, thermometer and a gas outlet for the preparation of chlorotetrahydropyran 1-1 four--necked, round-bottomed flask with a gas inlet tube, a dropping funnel, a mechanical stirrer and a thermometer, combined with a gas outlet for the preparation of HC=CMgBr and its reaction with chlorotetrahydropyran 1-1 three-necked, round--bottomed flask with a dropping funnel, combined with a gas inlet, a mechanical Stirrer and a thermometer, combined with a gas outlet for the conversion into the allenic alcohol. 

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

Alcaide, Aknendros and coworkers developed a combination of a 3,3-sigmatropic rearrangement of the methanesulfonate of an a-allenic alcohol to give a 1,3-bu-tadiene which is intercepted by a dienophile present in the molecule to undergo an intramolecular Diels-Alder reaction [83]. Thus, on treatment of 4-236 with CH3S02C1, the methanesulfonate was first formed as intermediate, and at higher temperature this underwent a transposition to give 4-237 (Scheme 4.51). This then led directly to the cycloadduct 4-238 via an exo transition state. 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

Petrov and coworkers [41] showed that the reaction of dibromides of alkenephos-phonic acids with acetylenic alcohols involved an acetylene-allene rearrangement. The products so formed hydrolyzed easily to the corresponding phosphinic acids. The latter on heterocyclization afforded 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives (Scheme 11). 

Burger2 has shown that alkynes undergo both Lewis acid-catalyzed and thermal carbonyl-yne reactions with 3,3,3-trifluoropyruvates to give allenes. Reaction of 1 (Equation (2)) occurs to give a 1 1 mixture of diastereomeric allenyl carbinols 2. Alternatively, reaction of hexyne 1 and methyl trifluoropyruvate with MgBr2-OEt2 at low temperature afforded 2 as an 8 1 mixture of diastereomers. The thermal reaction does not suffer from allylic alcohol byproducts arising from reaction of the substrate with the Lewis acid.3... 

In 1974, Vermeer et al. described formation of allenic alcohols 61 by the reaction of alkynyl epoxides 60 with Grignard reagents in the presence of 10mol% of Cul (Scheme 3.33) [71]. In the absence of Cul, a complicated mixture of products was obtained. Furthermore, the Cu-catalyzed reactions exhibited higher yields and higher selectivity than analogous reactions of alkynyl epoxides with lithium dialkylcup-rates [72], This method was applied to a reaction of allylmagnesium bromide with an alkynyl epoxide [73]. 

With the proper choice of reaction conditions, diastereoselective synthesis of a-allenic alcohols 69 and 70 from propargylic epoxide 68 was achieved [80, 81], With RMgBr and 5 mol% of CuBr/2PnBu3, anti allenic alcohols 69 are obtained with up to 100% diastereoselectivity. On the other hand, syn allenic alcohols 70 can be prepared with 88-96% diastereoselectivity with RMgCl, Me3SiCl and 5mol% CuBr (Scheme 3.36). 

In 1963, an asymmetric synthesis of chloroallenes was reported by the SNi reaction of propargyl alcohols with thionyl chloride [34]. Since then, rearrangement of pro-pargylic precursors has been one of the most useful methodologies for the synthesis of allenes [35]. Treatment of 84, obtained by asymmetric reduction with LiAlH4-Dar-von alcohol complex, with thionyl bromide gave 86 as the major product via 85 (Scheme 4.21) [36],... 

Spino and Frechette reported the synthesis of non-racemic allenic alcohol 168 by a combination of Shi s asymmetric epoxidation of 166 and its organocopper-mediat-ed ring-opening reaction (Scheme 4.43) [74]. Reduction of the ethynyl epoxide 169 with DIBAL-H stereoselectively gave the allenic alcohol 170, which was converted to mimulaxanthin 171 (Scheme 4.44) [75] (cf. Section 18.2.2). The DIBAL-H reduction was also applied in the conversion of 173 to the allene 174, which was a synthetic intermediate for peridinine 175 (Scheme 4.45) [76], The SN2 reduction of ethynyl epoxide 176 with DIBAL-H gave 177 (Scheme 4.46) [77]. 

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