Silyl ynolates

Metal ynolates are not as easy to prepare in a similar fashion as metal enolates, because the intermediates may be labile monosubstituted ketenes. Several preparative methods for alkali metal ynolates have been reported, among which some have been used as intermediate steps in one-pot organic syntheses. Silyl ynolates have been prepared from lithium ynolates. There have been few reports on the other metal ynolates. Since there is no universal method to determine the yield of metal ynolates, the efficiency of preparation is estimated from the results of some of the following reactions. 

Lithium acetylides 28 are oxygenated by lithium t-butylperoxide, prepared from anhydrous t-butylhydroperoxide and LHMDS, to give lithium ynolates 29 (equation 9) °. This method has been used as an efficient route for the preparation of the silyl ynolates 30" (Section V). Dioxygen, t-butyl perborate and bis(trimethylsilyl)peroxide have been unsuccessful as oxidation reagents " . ... 

Lithium ynolates are stable and keep their reactivity at 0 °C under inert gas for several days, but they decompose in 1 day at 20 Silyl ynolates (sUyl ynol ethers) are stable for a long period and they can be purified by distillation, but they are labile to acids (Section V). The stability of ynolates of metals other than hthium is unknown. 

Kozmin et al. applied enyne metathesis between olefin and silyl ynolate to the synthesis of two isomeric eremo-philanes (190 and 191, Scheme 24.48) isolated from the flowering plants of the Compositae family. RCM of 186 was carried out in the presence of [Ru]-II, and the subsequent treatment with HF gave enone 188. 

SCHEME 24.48. Application of enyne metathesis between olehn and silyl ynolate. 

An efficient preparation of hexahydro-isoxazolo[2,3- ]pyridin-2-ones relies on the anionic addition of nucleophiles at the electrophilic carbon of the nitrone followed by cyclization of the resulting Ar-oxide. As shown by results collected in Scheme 31, various nucleophiles can be engaged in the reaction and include enolates 95 <20020L3119> or 98 <2000BML1811>, silyl acetals 101 <2003TL2817>, or ynolates 103 <20020L3119> (Scheme 31). 

Ynolate anions react with acylsilanes at low temperature to give P-lactones 48 in good yields. When the reaction is conducted at room temperature the isolated product is a (1-silyl-a,p-unsaturated ester via a P-lactone enolate intermediate <02JACS6840>. 

This homologation via lithium ynolates has been used to prepare silyl ynol ethers, as described in Section V. 

Ynol tosylates are synthesized from terminal alkynes via a unique sequence (equation 10). The hypervalent organoiodine compound 32, prepared by treatment of iodosoben-zene diacetate with /i-toluenesulfonic acid, reacts with the terminal alkynes 31 to give the iodonium tosylates 33, which are then treated with 10 mol% of CuOTf or AgOTf to afford the ynol tosylates 34. Finally, the ynol tosylates 34 are converted into lithium ynolates 35 by treatment with MeLi. The ynolates are trapped with r-butyldimethylsilyl chloride, triethylgermyl chloride and tributylstannyl chloride to give the silyl ynol ethers 36, the germyl ketenes 37 and the stannyl ketene 38. ... 

The NMR spectrum of silyl-substituted potassium ynolates in THF-rfg shows signals at 132.8 and 33.4 ppm, which are close to those of alkynyl ethers. The IR spectrum in THF shows a strong absorption at 2229 cm , which is typical for alkyne . These results point to a metal ynolate rather than a metallated ketene. 

There has been only a few reports on reactions of small rings with metal ynolates. Oxiranes are much less electrophilic than carbonyls and sometimes need activation by Lewis acids or Lewis-acidic organometals. The lithium-trimethylaluminum ate complex of i/ZyZ-substituted ynolate 105 reacts with the oxirane 106 to give the y-lactone 107 (equation 44), while lithium silyl-substituted ynolates are inert to oxiranes. There have been no reports using carbon-substituted metal ynolates. 

The y-lactam 110 is prepared by the reaction of the lithium silyl-substituted ynolate 105 with the aziridine 108 activated by a p-toluenesulfonyl group. The initial product is the enolate 109, which can be acidified to yield the a-silyl-y-lactam 110. Intermediate 109 can be trapped by aldehydes to afford the a-alkylidene-y-lactams 111 via a Peterson reaction (equation 45) . These reactions may be considered to be formal [3 + 2] cycloadditions as well as tandem reactions involving nucleophilic ring opening and cyclization. 

Although the Michael addition of metal ynolates to a,/ -unsaturated carbonyl compounds is expected to give six-membered cycloadducts, 1,2-addition to carbonyl groups usually precedes 1,4-addition. The cycloaddition of the lithium-aluminum ate complex of silyl-substimted ynolate 112 with ethyl benzylideneacetoacetate (113), which is doubly activated by the ester and keto functions, gives the y-lactone 114 via a [4 4- 2] type cycloaddition (equation 46). Diethyl benzylidenemalonate (115) affords the uncyclized ketene 116 by reaction with 112 (equation 47). This could be taken as evidence for a stepwise mechanism for equation 46. ... 

Olefination of acylsilanes is expected to become a useful method for the preparation of vinylsilanes, which are a powerful synthetic tool . Olefination of the acylsilanes 135 with ynolates provides the -silyl-a,/S-unsaturated esters 136 in high yields with high Z-selectivity (equation 56) . In most cases, the E isomers could not be detected by H NMR and HPLC. This is the first general method for the stereoselective synthesis of tetrasubstituted olefins. 

Since sUyl ynol ethers have an electron-rich triple bond, they are useful for Lewis acid catalyzed synthetic reactions. Lithium ynolates 175 are silylated by TIPSCl or TIPSOTf and TBSCl to afford the corresponding silyl ynol ethers 176 and 177, which are thermally stable and isolable, but sensitive toward acids (equation 71) . See also equations 9 and 10 in Section ll.C. An experimentally improved procedure for the purification of 176 derived from Kowalski s method is described. Lithium ynolate derived from Julia s method is also used for the preparation of 176. TMSCl and TESCl provide silyl ketenes 179, however, by C-silylation. These small silyl chlorides primarily gave the silyl ynol ethers 178, but, upon warming the reaction mixture, isomerization to the more stable silyl ketenes takes place. The soft electrophilic silyl chlorides like PhsSiCl afford silyl ketenes. Disi-lyl ynol ethers, prepared from ynolate dianions, are rearranged to disilylketenes mediated by salts . 

Nucleophilic reactions of lithium thioalkynolates with electrophiles mostly occur at the 3 -position to afford alkynyl sulfides. For example, 3 -silylation and 3 -stannation are shown in equation 80 the synthesis and -alkylation of a quaternary ammonium thioalkynolate are shown in equation 81. Exceptionally, lithium thioalkynolates add to ketones to form -thiolactones, which are converted into alkenes on elimination of carbon oxysulfide (equation 82). Contrary to lithium ynolates, thioalkynolates do not react with aldehydes. ... 

Both types of reactivity of ynolate anion have been reported in the literature. The O-attack is typical for the reactions of lithium ynolates with trialkylchlorosilanes b24,25 dialkyIchlorophosphates. Lithium ynolates, generated as shown in equations 5-10, react with sterically hindered trialkylchlorosilanes in THF affording silyl ynol ethers as primary products (equation 12). However, in some cases the silyl ynol ethers are unstable at room temperature and isomerization to the more stable ketenes, or decomposition, occurs The ketene rearrangement usually occurs in reactions of lithium alkynolates with methyl substituted silyl chlorides a typical example of such a rearrangement is represented by reaction 13 ". ... 

Addition of lithium ynolates generated from eth mylsilyl ethers with silyl vinyl ketenes gave highly substituted benzenes (eq 13). TIPS protection, in contrast to TBDMS, allowed preparation and purification by distillation and silica gel chromatography of these sensitive starting materials. 

Formation of Silyl Ynol Ethers. Esters can also be transformed into triisopropylsilyl 3mol ethers. The ester is first converted to the ynolate anion, followed by treatment with TIPSCl to... 

A silyl-substituted ynolate 141 undergoes cycloaddition to A-sulfonyl aldimines 142, followed by ring opening, to afford the a,p-unsaturated amide 143 at 20 °C (Fig. 52) [39]. This stereoselectivity is unexpected for the torquoselective olefination. The steric interaction between bulky MeaSi and the phenyl groups may be critical. A-o-Methoxyphenylaldimines 144 with ynolates at room temperature produce a,(3-unsaturated amides 145 in good yield with high -selectivity (Fig. 53) [122], Since the double adduct 146 is produced as an intermediate, the process involves the retro-Mannich reaction. 

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