Enolates, alkenylation

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Aryl halides react with a wide variety of aryl-, alkenyl- and alkylstan-nanes[548-550]. Coupling of an aryl tritlate with an arylstannane is a good preparative method for diaryls such as 688. The coupling of alkenylstannanes with alkenyl halides proceeds stereospecifically to give conjugated dienes 689. The allylstannane 690 is used for allylation[397,546,551-553]. Aryl and enol triflates react with organostannanes smoothly in the presence of LiCl[554]. 

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[60i] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of siiyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

The key step in the total synthesis of rhizobitoxine is the Pd-catalyzed exchange reaction of the methyl alkenyl ether moiety in 4 with the functionalized alcohol, although the yield is low[3]. The enol pyruvate 6 (a-ethoxyacrylic acid) is prepared by the reaction of methyl a-methoxyacrylate or a-methoxy-acrylic acid (5) with ethanol catalyzed by PdCl2(PhCN)2 at room temperature in the presence of CuCli and NaH2P04[4],... 

Hop "bitter" acids are isomeric mixtures of cyclohexadienone stmctures in both keto and enol forms, substituted at various positions on the ring by hydroxyl, acyl, and alkenyl groups. See Figure 2. 

Acetylation of acetals or ketals can be accomplished with acetic anhydride and BF3-etherate. ° The mechanism with acetals or ketals also Involves attack at an alkenyl carbon, since enol ethers are intermediates. Ketones can be formylated in the a position by treatment with CO and a strong base. ... 

This section contains syntheses of enol esters and esters of unsaturated acids as well as ester molecules bearing a remote alkenyl unit. 

Enol ethers are found in this section as well as alkenyl ethers. 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

In the fourth and final step, the intermediate 2-(2,-hydroxyphenyl)ethen-l-sulfmate (HPESi ) is desulfinated to 2-(2 -hydroxyphenyl)ethan 1-al (HPEal). As seen from Fig. 4, this step cannot be catalyzed by the arylsulfinate desulfinase like DszB. Instead, the enzyme has to be an alkenylsulfmate desulfinase. The alkenyl C-S bond as present in the intermediate, can only be desulfurized by hydroxylase-type enzyme, giving an enol, which can then tautomerize to HPEal and sulfite. However, the identity of the sulfur-containing product has not been confirmed [34],... 

Silyl enol ethers of alkenyl methyl ketones can be efficiently cyclized to cyclopentenones and cyclohexenones by treating them with stoichiometric amounts of palladium acetate244 an example indicating the elaboration of this approach to the synthesis of a reduced benzoxepinone derivative, and the suggested244 mechanism of the reaction, are depicted in Scheme 174. 

Alkenyl trifluoromethanesulphonates (enol triflates) undergo Heck coupling with alkenes efficiently (equation 123)209a 215. This reaction is a useful variation of the use of vinyl halides not only because they are easy to prepare from the corresponding carbonyl compounds, but also because yields are good, and the stereochemistry of the triflate is largely maintained. 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

Shibasaki et al. also developed catalytic reactions of copper, some of which can be applied to catalytic asymmetric reactions. Catalytic aldol reactions of silicon enolates to ketones proceed using catalytic amounts of CuF (2.5 mol%) and a stoichiometric amount of (EtO)3SiF (120 mol%) (Scheme 104).500 Enantioselective alkenylation catalyzed by a complex derived from CuF and a chiral diphosphine ligand 237 is shown in Scheme 105.501 Catalytic cyanomethyla-tion by using TMSCH2CN was also reported, as shown in Scheme 106.502... 

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