Hydroxy allenes

Sollen a-Hydroxy-allene Zicl der Reduktion sein, so ist es giinstig, die Hydroxy-Gruppe, die entfernt werden soil, mit 5,6-Dihydro-4H-pyranzu acetalysieren8. Die gewiinsch-ten a-Hydroxy-allene fallen in Ausbeuten von 73-95% d.Th. an1 ... 

Durch Reduktion der aus einem Propargylalkohol, Dimethylamino-methanol und Me-thyljodid erhaltenen quartaren Ammonium-Salze mit Natrium-bis-[2-methoxy-athoxy]-dihydrido-aluminat werden ebenfalls a-Hydroxy-allene erhalten z.B.1... 

Enzymes such as pig liver esterase have been successfully applied in enantioselective hydrolysis of allenyl esters on a scale of 2 mmoles131. This provides the enantiomerically enriched allene-carboxylic acid as well as the ester of opposite configuration, by what is in fact a catalytic kinetic resolution (6-90% oy). Conversely, partial enantioselective esterification of /1-hydroxy-allenes (3-72% oy) employing lipases has been reported132,133. 

An alternative catalytic system for exo-selective cycloisomerizations of hydroxy-allenes was reported by Toste et and takes advantage of a chiral... 

In 2006, Widenhoefer reported an effective gold(I)-catalyzed protocol for the exo-hydroalkoxylation of y- and 6-hydroxy allenes to form 2-vinyl tetrahydrofurans and 2-vinyl tetrahydropyrans, respectively [104]. For example, treatment of 1-phenyl-5,6-heptadienol with a catalytic 1 1 mixture of [P(f-Bu)20-biphenyl]AuCl and AgOTs in toluene at room temperature led to isolation of 2-phenyl-6-vinyltetrahydropyran in 96% yield as a 7.2 1 mixture of diastereomers (Eq. (12.33)). This gold(I)-catalyzed hydroalkoxylation protocol tolerated substitution at the terminal allenyl carbon atoms and along the alkyl chain that tethered the hydroxy group to the allenyl moiety and was also effective for the S-exo hydroalkoxylation of y-hydroxy allenes. Alcaide and Almendros have shown that gold(III) also catalyzes the S-exo hydroalkoxylation of y-allenyl alcohols in modest yields (Eq. (12.34)) [105]. 

Toste and coworkers have developed effective gold(I)-catalyzed protocols for the intramolecular enantioselective hydroalkoxylation of y- and 8-hydroxy allenes employing chiral, enantiomerically pure silver salts [107]. For example, treatment of y-hydroxy allene 66 with a catalytic 1 2 mixture of the achiral bis(gold) complex (dppm)Au2Cl2 [dppm = bis(diphenylphosphino)methane] and chiral silver phos-phonate Ag-(J )-67 in benzene at room temperature led to isolation of 2-alkenyl tetrahydrofuran 68 in 90% yield with 97% ee (Eq. (12.36)). A combination of chiral bis(gold) complex with a chiral silver salt proved effective for terminally unsubstituted allenyl alcohols. For example, reaction of 5,6-heptadienol catalyzed by a mixture of [(S,S)-DIPAMP]Au2Cl2 [DIPAMP = l,2-ethanediylbis[(2-methoxyphenyl) phenylphosphine] and Ag-(J )-67 gave 2-vinyltetrahydropyran 69 in 96% yield with 92% ee (Eq. (12.37)). 

A Cg hydroxy allenic acid (8-OH 2,3-8 2 stillingic) is present in stillingia oil (8-10%) where it is associated with 2f4c-10 2 to make a C,g estolide. Many Cjj allenic acids have been synthesised. 

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. ... 

Recent work has demonstrated that hydroperoxides of a-ketols are formed from the corresponding hydroperioxide precursors by conversion of hydroperoxides into a-ketols and following lipoxygenase oxidation of a-ketols [3]. The present work has revealed that the similar metabolites (a- and y-ketols of hydroxy derivatives) may be formed from double dioxygenation products by dehydration of hydroperoxide groups and further hydrolysis of hydroxy allene oxides. 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Arai Y., Koizumi T. Synthesis and Asymmetric Diels-Alder Reactions of Chiral. Alpha.,.Beta.-Unsaturated Sulfoxides Bearing a 2-Exo-Hydroxy-lO-Bornyl Group As an Efficient Ligand on the Sulfur Center Rev. Heteroat. Chem. 1992 6 202-217 Keywords allenic sulfoxide, a-sulfinylmaleate, a-sulfinylmaleimide, asymmetric synthesis, chiral unsaturated sulfoxides... 

Allenic alcohols couple with allyl indium reagents at 140°C to give allylic alcohol products. Similarly, (o-hydroxy lactones couple with organoindium reagents. 

Homoricinstearolic Acid, and two Fatty Hydroxy-acids with Allenic Side-Branches. J. Chem. Soc. [London] 1957, 1622. 

Additional hypotheses concerning prostaglandin biosynthesis in P. homomalla resulted from isolation of 11R-HETE (76) from the polar lipid fraction [95]. Apparently, 11R-HETE (76) is also a minor product of incubations of arachidonic acid with acetone powder preparations of P. homomalla [95], In this alternate hypothesis (Scheme 8), an 11-hydroxy or 11-hydroperoxy-8,9-allene oxide intermediate is formed from a sequence of oxidations at C8 and Cll. Opening of the allene oxide to a transient C8 earboeation induces eycli-zation with a consequent addition of water to C15. This proposed pathway leads initially to formation of PGE2 (16 or 38), which following acetylation, elimination of acetic acid from Cl 1-12, and esterification, forms the observed major natural product in the coral, 15-acetoxy methyl PGA2 (36 or 54). Notably, if... 

Chiral 2,5-dihydrofuran can be prepared through the HC1 gas promoted cyclization of the corresponding optically active allenic hydroxy-ester 83 with almost complete axis chirality (87% ee) to center chirality (85% ee) transfer <00TL9613>. 

Pyrrolo[l,2- ][l,2]oxazines are a class of compounds with very few references regarding synthesis and reactivity. An interesting preparation has been described by intramolecular cyclization of IV-hydroxy pyrrolidines carrying a methoxyallene substituent at C-2 (242, Scheme 32). These compounds were obtained by addition of a lithiated allene to chiral cyclic nitrones 241. Cyclization occurred spontaneously after some days at relatively high dilution (0.05 M). Compounds 243 (obtained with excellent diastereoselectivity) can be submitted to further elaboration of the double bond or to hydrogenolysis of the N-O bond to form chiral pyrrolidine derivatives (Section 11.11.6.1) <2003EJ01153>. 

Not least for the syntheses of natural products, alkoxycarbonylations with formation of allenic esters, often starting from mesylates or carbonates of type 89, are of great importance [35, 137]. In the case of carbonates, the formation of the products 96 occurs by decarboxylation of 94 to give the intermediates 95 (Scheme 7.14). The mesylates 97 are preferred to the analogous carbonates for the alkoxycarbonylation of optically active propargylic compounds in order to decrease the loss of optical purity in the products 98 [15]. In addition to the simple propargylic compounds of type 89, cyclic carbonates or epoxides such as 99 can also be used [138]. The obtained products 100 contain an additional hydroxy function. 

Similarly, treatment of a-tosylamino-substituted allene 83 provided the expected a-amino ester 232 in good yield [74], The analogous reaction could also be performed with methoxyallene-aziridine adduct 46, which furnished enantiomerically pure /3-amino acid 233 [46], Although the ozonolysis approach seems to constitute a versatile and flexible method for the construction of a-amino and a-hydroxy esters, only a few examples have been reported so far. 

A few nitrogen-substituted allenes themselves are known as biologically active compounds [154], For example, the 9-(4 -hydroxy-1, 2 -butadienyl)adenine (268a) was found to inhibit in vitro replication and cytopathic effects of human immunodeficiency viruses HIV-1 and HIV-2 [155], More recently, an increase in the anti-HIV activity in cell cultures using the adenallene phosphotriester derivative 268b was reported (Scheme 8.72) [156]. 

In contrast to the rich chemistry of alkoxy- and aryloxyallenes, synthetic applications of nitrogen-substituted allenes are much less developed. Lithiation at the C-l position followed by addition of electrophiles can also be applied to nitrogen-containing allenes [10]. Some representative examples with dimethyl sulfide and carbonyl compounds are depicted in Scheme 8.73 [147, 157]. a-Hydroxy-substituted (benzotriazo-le) allenes 272 are accessible in a one-pot procedure described by Katritzky and Verin, who generated allenyl anion 271 and trapped it with carbonyl compounds to furnish products 272 [147]. The subsequent cyclization of 272 leading to dihydro-furan derivative 273 was achieved under similar conditions to those already mentioned for oxygen-substituted allenes. 

Some interesting modifications with respect to the base-induced isomerization have recently been developed. For example, conversion of 4-hydroxy-l-thiophenyl-2-alkynes 299 into the corresponding 4-hydroxy-substituted thiophenylallenes 300 was achieved by treatment with potassium hexamethyldisilazide at low temperature (Scheme 8.79) [165], If the hydroxyl group is protected as the THP ether an elimination reaction occurred, resulting in the formation of an enyne instead of allene 300. 

The iodohydroxylation of 1,2-allenyl sulfoxide 171 with I2 in the presence of H20 exhibits E-selectivity leading to (E)-2-iodo-3-hydroxy-l-alkenyl sulfoxide [88]. By using Br2, CuBr2 or NBS, (E)-2-bromo-3-hydroxy-l-alkenyl sulfoxide is produced. For the chlorohydroxylation of a sulfoxide, CuCl2 and silica gel were used to mix with the sulfoxide to deliver the (E)-chlorohydroxylation products highly stereoselec-tively [88]. The chirality in the allene moiety can be efficiently transferred to the final allylic alcohols. Under the catalysis of a Pd or Ni complex, the C-X and C-S bonds can be coupled to introduce different substituent(s) into the different locations of the C=C bond. 

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