Allenic hydroxy ketones

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

It is also possible to oxidize allenes 89 and 92 to unsaturated hydroxy ketones 91 and 93 via the spirodioxide intermediate 90 [29]. In this case the terminating step is a 1,5-proton shift. In the examples shown in Scheme 17.26, the formation of the spirodioxide intermediate is diastereoselective, as is the rearrangement to the unsaturated hydroxy ketone. 

The catalytic asymmetric diboration of allenes provides a-substituted 2-boronyl allylic boronates of type 25 (see Eq. 32). One of them, 91, adds to ben-zaldehyde, albeit with a slight erosion of stereoselectivity (Eq. 65). The major P-hydroxy ketone stereoisomer, isolated after an oxidative work-up, originates from the putative chairlike transition structure 92. 

In tetrakis(trifluoromethyl)allene (9), potassium permanganate in acetonitrile hydroxylates only one C = C bond 93 the resulting enol tautomerizes to an a-hydroxy ketone 10. The reaction has been repeated and extended to other perfluoroalkylated allenes92 achieving yields of 51-60%. 

Asymmetric, osmium-catalysed dihydroxylation of 1,1-disubstituted and 1,3-disub stituted allenes has been employed to synthesize chiral a-hydroxy ketones, a,a - (g) Dihydroxy ketones were obtained from 1,3-disubstituted allenes with high enantio-... 

The PTC reaction of fulvenes with CO/Mel gives monoacylated derivatives as the major products [155]. Metal-carbonyl catalyzed reactions of allenes have also been affected under PTC conditions (eq. (14)). Nickel cyanide catalyzes the re-giospecific carbonylation of allenes to y9,y-unsaturated acids [ 156] while hydroxy-ketones are usually the main products when Co2(CO)g and Mel are used [157]. The PTC reaction of allenes with CO in the presence of Mn2(CO)io and Mel afford (Z)-a,y5-unsaturated ketones [158]. 

Dihydroxy allenes are generated from ketoenes and ethynyl epoxides. a,P-Epoxy ketones undergo reductive cleavage but the P-hydroxy ketones thus obtained can react further, for example with an e, -double bond to give cyclic 1,3-diols. Note that the double bond does not have to be activated, and furthermore, a silylalkyne moiety and a tricarbonylchromium-complexed arene can play the same role, although in the latter case the net result is a cine-substitution. 

A key step in the synthesis of 12-epi-lycopodine reported by Wiesner and coworkers is the intramolecular [2 + 2] photocycloaddition of a vinylogous imide and an allene. Irradiation of photosubstrate 46 produced a single cyclobutane 47, in which the allene added to the vinylogous imide anti to the methyl group (Scheme 13)3 Photoadduct 47 was converted to ketal-alcohol 48 via a three-step sequence of ketalization, epoxida-tion and reduction. Hydrolysis of the ketal unmasked the / -hydroxy ketone functionality. Retro-aldol fragmentation followed by aldol closure gave hydroxyketone 49, which was readily converted to the polycyclic alkaloid 12-epi-lycopodine. 

The isomerisation of 15,15 -cis-/5-carotene to the all-trans isomer is catalysed by singlet oxygen. Under more vigorous conditions 5,6-oxides, 5,8-oxides, hydroxy-ketones, allenes, and acetylenes were claimed. Further oxidation broke up the carbon skeleton to give /5-ionone, dihydroactinidiolide (99), and... 

Phase-transfer-catalysed reactions of allenes with dicobalt octacarbonyl, methyl iodide, and carbon monoxide, at room temperature and atmospheric pressure, afford unsaturated hydroxy ketones and dienones. Although the yields are not high, the method constitutes a simple one-pot procedure for the synthesis of an interesting class of compounds not easily accessible by other means. 

Z-Trisubstituted allylic alcohols are obtained from protected a-hydroxy-ketones in a lithium-free Wittig reaction and 1-bromo-olefins (and hence acetylenes) are produced from the reaction of Ph3P=CHBr with aldehydes. References to two syntheses of substituted-allenes have appeared Ph3P=C(R )C02R and R R C=C=0 (generated in situ from the acid chloride... 

Recently, Trost et al. reported the vanadium-catalyzed addition reaction of 2,3-allenols [180], Here the oxygen in 401 served as an intramolecular nucleophile to attack the center carbon atom of allene to form a vanadium enolate 402. Aldol condensation of 402 with an aldehyde afforded (2-hydroxy)alkyl vinylic ketones 403. 

An interesting novel coupling reaction of allenes with carbonyl compounds mediated by a lanthanide metal species was reported recently [80], The samarium(II) iodide-mediated reaction of various ketones or aldehydes 153 with methoxyallene (56) afforded exclusively y-addition products 4-hydroxy-l-enol ethers 154 in moderate to good yields with low cis/trans selectivity (Scheme 14.39). 

The reaction of 2-aminopyridine hydrochlorides and allenic nitriles either neat at 90°C for 20 hours or in boiling methylene chloride for 15 hours afforded unstable 2-imino-2//-pyrido[l,2-a]pyrimidine hydrochlorides 71, which could be isolated as hydrates in about 50% yield [88JCS(P1)975]. If the reactions were carried out in boiling 95% ethanol for 72 hours, the initially formed 2-imino-2//-pyrido[ 1,2-a Ipyrimidines 71 were hydrolyzed and 2-pyridyl ketones 73 could be isolated. Under the latter conditions 3-hydroxy-2-aminopyridine gave 2-iminopyridopyrimidines 74, which were stabilized by the formation of zwitterionic structures (Scheme 5). [Earlier the ring-opened products 73 (R = H, 3-NH2) were described as a 4-imino-4/7-pyrido[ 1,2-a]pyrimidine derivative 72 (81TL4127)]. 

The reaction of linalool with boron trifluoride etherate has been re-examined no pinenes or camphene were obtained.146 Dehydrolinalool reacts with methyl iso-propenyl ether under acidic conditions by Claisen rearrangement to give the allene (58).147 Further papers in this section include reaction of monoterpenoid alcohols with paraformaldehyde-acetic anhydride-sodium acetate,148 rearrangement of the alcohol (47 X = OH) to the oxabicycloheptane (59) and the ketone (60),149 and the rearrangement of a typical monoterpenoid vicinal hydroxy-ester to an epoxide.150... 

When pyrolyzed, p-hydroxy alkenes cleave to give alkenes and aldehydes or ketones." Alkenes produced this way are quite pure, since there are no side reactions. The mechanism has been shown to be pericyclic, primarily by observations that the kinetics are first order" and that, for ROD, the deuterium appeared in the allylic position of the new alkene." This mechanism is the reverse of that for the oxygen analog of the ene synthesis (16-54). p-Hydroxyacetylenes react similarly to give the corresponding allenes and carbonyl compounds." " The mechanism is the same despite the linear geometry of the triple bonds. 

Whereas the cycloisomerization of allenic ketones affords achiral products, replacing the keto with a hydroxy group leads to the formation of chiral heterocycles. In 2001, the synthesis of chiral 2,5-dihydrofurans by treatment of a-hydroxyallenes with catalytic amounts of AuCls in unpolar solvents was reported (Scheme 4-90). Many functionalities (e.g., carbonyl groups, additional free alcohols, and acid-sensitive... 

A new thiophen synthesis is based on deprotonation and cyclization of the resultant carbanion (65) of a keten dimethylthioacetal. Other applications of cr-(phenylthio)- or cr-(alkylthio)-alkyl-lithiums include preparations of disparlure (the sex pheromone of the gypsy moth) and other chiral epoxides,of an anti-peptic-ulcer diterpene from Croton sublyratus, of carbene-thiometal chelates through reaction with fCr(CO)gl or fW(CO)jl, of olefins via )ff-hydroxy-sulphides, and of Michael adducts of enones. In other work, the chiral solvent l,4-dimethylamino-2,3-dimethoxybutane is employed in enantioselective addition reactions of cr-thio-carbanions with ketones and Michael acceptors. a,P -Elimination of cr-thio-carbanions such as (66) provides a useful synthesis of olefins, and a 2-(lithiomethylthio)-A -oxazoline (67) has been used to prepare a C-labelled thiiran for a microwave study of the valence tautomerism of allene episulphide. ... 

Dihydrofurans and Tetrahydrofurans.—Silver (i)-catalysed cyclizations of allenic alcohols lead to 2,5-dihydrofurans in moderate yields (Scheme 23). ° Dimethylsulphonium methylide reacts smoothly with o- and p-hydroxy-benzylidene ketones to yield 2,5-dihydrofurans. " Quinone methides, as inter-... 

A similar transformation with iV-monosubstituted allenic carboxamides targeting lactams yields mixtures of imino dihydrofu-rans and the desired pyrrolidones whereas AgNOs-promoted cyclization of a-hydroxy allenes leads to 2,5-dihydrofurans, the same mild conditions allow conversion of allenyl ketones and aldehydes to their corresponding furan derivatives. A comparative overview concerning the reaction of these substrates with other metal salts or Lewis acid catalysts (HgClOa, PdCl2(MeCN)2, etc.) points out differences in product distribution. ... 

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