Allenes reactions with alcohols

The reaction pathway depends on the steric hindrance and/or the electron density of the allene moiety. With alcohols bearing a less or unsubstituted allene moiety, the addition of CaC03 may help the cyclization [166,167]. 

Hydroxy(tosyloxy)iodo]benzene and Its Analogues Reactionswith Alkenes and Allenes. Reactions with Alkynes and Alcohols. Reactions with Keto Compounds. Reactions with Nitrogen, Sulfur, and Other compounds. 

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). 

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... 

Carreira and co-workers developed a highly efficient enantioselective addition of terminal alkynes to aldehydes giving propargyl alcohols by the mediation of zinc tri-flate and N-methylephedrine [17]. This reaction serves as a convenient and powerful synthetic route to a wide variety of enantioenriched allenes via propargyl alcohols. Dieter and Yu applied this alkynylation to the asymmetric synthesis of allenes (Scheme 4.12) [18]. Reaction of phenylacetylene with isobutyraldehyde afforded the propargyl alcohol in 80% yield with 99% ee, which was mesylated to 49 in quantitative yield. Reaction of 49 with the cyanocuprate 50 afforded the desired allene 51 with 83% ee. 

Additional allene homologues were prepared by using this methodology with a variety of electrophiles (EX, Table 9.2) [6], For reactions requiring removal of a secondary allenic proton the base of choice was tBuLi. Only allenic products were formed except in the reaction with cyclopentanone, in which a small amount of the homopropargylic alcohol product was produced (last entry). 

These reactions are thought to proceed by initial formation of the lithio propargylic alcohol adduct, which undergoes a reversible Brook rearrangement (Eq. 9.14). The resulting propargyllithium species can equilibrate with the allenyl isomer and subsequent reaction with the alkyl iodide electrophile takes place at the allenic site. An intramolecular version of this alkylation reaction leads to cyclic allenylidene products (Eq. 9.15). 

Reaction of the transient zinc intermediates with various electrophiles yielded the acetylenic substitution products and only minor amounts of allenes (Table 9.49). Reactions with aldehydes were non-selective, affording mixtures of stereo- and regioisomeric adducts. However, prior addition of ZnCl2 resulted in the formation of the homopropargylic alcohol adducts with high preference for the anti adduct, as would be expected for an allenylzinc chloride intermediate (Table 9.50). 

Even the reaction with 1,1-disubstituted allenes delivered 2-chloroallyl alcohols 16 with the hydroxyl group connected to the more substituted terminus [15]. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

The dispersity or homogeneity of the reductant in a reaction system sometimes plays a decisive role. It is also important for synthetic practice. Crandall and Mualla (1986) compared reduction of 7-methylocta-5,6-diene-2-one [H3C-C(CH3)=C=CH-CH2-CH2-C(0)-CH3] in THF by the action of naphthalene-sodium, on the one hand and, by sonically activated sodium on the other. In both the cases, one-electron transfer yields the anion-radical salt of the allenic ketone with sodium. However, only in the case of sonicated sodium is this salt stabilized, eventually giving H3C-C(CH3)=C=CH-CH2-CH2-C(0H)-CH3 along with cyclic products (l-methyl-2-isopropylidene cyclopentanol and l-methyl-2-isopropylcyclopent-2-enol). If naphthalene-sodium is used, only the cyclic alcohols are obtained as mentioned earlier. 

Significantly, silylcuprates react with carbamates with syn stereoselectivity59, similar to their reactions with organocuprates62, whereas other nucleofugal groups, such as acetate or methanesulfonate, are displaced in an anti fashion23,27,57. Thus, both enantiomeric (or epimeric) allenes can be obtained from the same propynyl alcohol precursor. 

Secondary and tertiary propargyl alcohols are directly converted to halo-allenes on reaction with concentrated aqueous hydrogen halides in the presence of the corresponding cuprous halide [60,72-73]. (See Table VII.) Better yields are obtained with hydrogen bromide. Hydrogen chloride yields chloroallene, propargyl chloride, and the chloro- 1,3-diene isomers (Eq. 60). 

Propargyl alcohols may be converted to allenes by several methods, for example, (a) through the intermediate formation of propargyl halides which are not isolated but react directly with cuprous salts and hydrogen halide [60, 72-73] or cyanide [71] (b) typical alcohol reactions with thionyl chloride [74a-d] phosphorus halides [75-77], and miscellaneous reagents (see Scheme 3). 

The products from this reaction are not invariably homogeneous since the first formed alkyne may isomerise, probably by way of an intermediate allene. With alcoholic potassium hydroxide at 170-180 °C, for example, terminal alkynes tend to rearrange to internal alkynes. The rearrangement process may be minimised by using sodamide in liquid ammonia as the reagent. 

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