Ketones, allenyl synthesis

Species (30) derived from RCHO and CH2=C(Li)SEt are isomerized by acid to a-thiolated ketones.Oxidation to sulphoxide and elimination gives the unsaturated ketone. Allenyl analogues of the above reagent add to epoxides to give products which can undergo further useful synthetic modification. The Shapiro method for the generation of vinyl-lithiums from sulphonyl hydrazones has been applied to a new one-pot synthesis of a-methylene-y-lactones involving elimination and carboxylation of the trianionic intermediate (31). ... 

The Doering-Moore-Skattebol method including a cyclopropylidene-allene rearrangement is often used for the synthesis of allenes. However, the reaction conditions applied are often not compatible with acceptor substituents. One of the rare exceptions is the transformation 76 —> 77 (Scheme 7.11) [122]. The oximes 77 are not accessible by the classical route starting from allenyl ketone and hydroxylamine (see Section 7.3.2). 

Finally, the synthesis of allenyl ketones is also possible by carbonylation if carbonates 103 are treated with C-H acidic compounds 104 such as /3-diketones or derivatives of malonic ester to yield products of type 105 [143],... 

The elimination reactions of /l-acetoxy sulfones 114 to give the donor-acceptor-substituted allenes 115 by a Julia-Lythgoe process are less conventional (Scheme 7.18) [157]. A new one-step synthesis of allene-l,3-dicarboxylates 118 from acetone derivatives 116 was developed by the use of 2-chloro-l,3-dimethylimidazolinium chloride 117 [158, 159]. This elimination of water follows also the general Scheme 7.17 if a derivative of the enol, resulting from 116, is assumed as an intermediate for an elimination step. More complex processes of starting materials 119 furnished allenyl ketones 120 in high yields [160-162]. 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

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],... 

Steps in total syntheses are the conversion of the macrocycic allenyl ketone 92 to the furanophane 93 in the synthesis of the enantiomer of rubifolide (Scheme 15.23) [53] and different steps in other references [54, 55]. 

The conversion of a diol or bromohydrin to the corresponding epoxide is a well-known and useful method. Recently two methods have been reported that significantly add to this chemistry. A synthesis of a key component of the natural product neocarzinostatin has been reported <07OL45>. In this work, an allenyl zinc bromide was added to a propargylic ketone to provide a chlorohydrin stereoselectively. Treatment of the chlorohydrin with base provided the epoxide. 

Terminal disubstituted allenyl ketones were used in the synthesis of tri- and tetra-substituted furans in the presence of In(OTf)3 and other metal salts as catalyst. In this reaction, a 1,2-shift of a terminal alkyl group is a key step <07AGE5195>. 

The cycloisomerization of allenyl ketones can be exploited for the synthesis of 2,3,4- or 2,3,5-trisubstituted and tetrasubstituted furans, when the Pd(0)-catalyzed cyclization of a,7-disubstituted substrates is combined with the coupling of an aryl halide or substituted allyl halide, as has been reported by Ma et al. (Equation 14) <20000L941, 2000CC117, 2003CEJ2447>. 

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... 

In general, synthesis of 4-isoxazolines is accomplished via three routes 1,3-dipolar cycloaddition of nitrones to alkynes or by the oximation of a,i -ethylenic ketones, a-alkynic ketones and aldehydes or from the selective reduction of isoxazolium salts. The nitrone (262) underwent tandem cyclo-addition-[2,3]sigmatropic rearrangement with allenyl sulfoxide (263). And it resulted in 4-isoxazoline (264) (Equation (46)) <89TL663>. 

The synthesis of the steroidal allenyl ketones (207) and (208) by treatment of the acid fluoride (206) with dimethylcadmium has been described. Reaction of lithium dimethylcopper with (206) gave mainly the alkylated )Sy-unsaturated ketone (209). °"... 

We have also shown that under the catalysis of Pd(PPh3)4 and Ag2C03, the coupling cyclization of 1,2-allenyl ketones with organic halides afforded poly-substituted furans (Scheme 6). The diversity of the reaction depends on the structures of the two starting materials, i.e., once the expected substituent is in a certain location of two starting materials, it can be assembled into the expected location of polysubstituted furans. However, for the synthesis of tetra-substituted furans, the reaction should be carried out in the presence of 20 mol% of n-Bu4N Br in DMA (conditions B). 

Transition metal-catalyzed cydoisomerization of allenyl ketones into furan products was first introduced by Marshall. In the first report from this group, it was demonstrated that various alkyl-substituted furans 2 could be prepared in high yields via the Ag-[50] or the Rh(I)-catalyzed [85, 86] cydoisomerization of allenyl ketones 1 (Scheme 8.1) [87]. This type of transformation of allenyl ketones [88-90] proved to be highly effident for the synthesis of up-to-trisubstituted furans. Furthermore, Marshall applied this strategy as the key step in the construction of the 2,5-disubstituted furanocycle 2a (Scheme 8.2) [87]. 

A recent report from Kirsch s group illustrated that vinyl propargyl ethers 36, as surrogates of skipped allenyl ketones 37, could be employed in a very efficient synthesis of densely substituted pyrroles 29S via the Ag/Au(I)-catalyzed... 

Trifluoromethyl)allyltrimethylsilane results frwith aldehydes and ketones gives trifluoromethyl-ated alcohols and silyl ethers. Synthesis of allyl and allenyl-silanes is stereospecific from hydroalumination or hydroboration of... 

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