Alkynyl acetals

Methylene chromans can be prepared by a palladium-catalyzed intramolecular cyclization of 2-iodophenyl alkynyl ethers 455. Simple modifications to the reaction conditions lead to either (E)- or (Z)-4-methylene chromans (Scheme 103) <2001TL2657>. 2-Iodophenyl alkynyl acetals are also viable substrates for this reaction <2005JOG489>. Addition of tris(2,6-diphenylbenzyl)tin hydride (TDTH) to a triethylborane-mediated intramolecular cyclization of 2-iodophenyl alkynyl ethers ensures complete (A)-selectivity is observed in the resulting 4-methylene chroman <2001AGE411>. 

Optically pure propargylic alcohols have been obtained by reductive cleavages of a,S-alkynyl acetals with organoaluminium reagents followed by oxidative removal of the chiral auxiliary (Scheme 18), and the same research group has achieved direct, highly efficient... 

Next, Gevorgyan et al. disclosed an alternative route to tetrasubstituted and even fused furans via a transition metal-catalyzed migratory cydoisomerization of skipped propargylic systems. Thus, syntheses of 3-acyloxyfurans 69 from alkynyl acetates 68 occurred with a formal 1,2-migration in the presence of 5 mol% of Ag-catalyst at room temperature (Scheme 8.28) [139,140[. Several other transition metals such as Cu(II),... 

Similarly, acetalic C-H bond could be exploited as hydride donor as well, and via ruthenium-catalyzed cyclization of linear alkynyl acetals 181, spirobicycles 182 could be furnished in fairly good yield (Scheme 69) [76], along with the formation of linear hydroxyester 183, which was generated by hydrolysis of intermediate I. Notably, rigid cyclic acetal afforded a higher yield of spiro compound in comparison to the linear acetals [96]. 

Spiro- and fused bicyclic structures were produced by using linear alkynyl acetals, ethers, or amines by means of a Cp RuCl(cod)-catalyzed intramolecular carbene insertion into Csp3-H bonds [119] [Eq. (56)]. The proposed mechanism invokes a 1,5- or 1,6-hydride shift onto a ruthenium vinylcarbene intermediate followed by reductive elimination leading to cyclized compounds. 

Balog A, Curran DP. Ring enlarging annulations. A one step conversion of cyclic silyl acyloins and w-alkynyl acetals to polycyclic enediones.i. Org. Chem. 1995 60 337-344. 

In the presence of a stoichiometric amount of diazo compound N2CHTMS and a catalytic amount of complex [CpRu(cod)Cl], various linear alkynyl acetals, ethers, and amines (101) have been transformed into valuable spiro- or fused bicyclic products (102) (Scheme 9). °° The mechanistic proposal of this Ru(II)-catalysed intramolecular process relies on the initial formation of Ru-vinyl carbenoid (103) that subsequently forms the expected products via a 1,5- (or 1,6-) Q s-H insertion process. 

Figure 2 Asymmetric hydrolysis of ( )-l-alkyl-2-alkynyl acetates.

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

The 2,3-alkadienyl acetate 851 reacts with terminal alkynes to give the 2-alkynyl-1,3-diene derivative 852 without using Cul and a base. In the absence of other reactants, the terminal alkyne 853 is formed by an unusual elimination as an intermediate, which reacts further with 851 to give the dimer 854. Hydrogenolysis of 851 with formic acid affords the 2, 4-diene 855[524]. 

Terminal alkynes react with propargylic carbonates at room temperature to afford the alka-l, 2-dien-4-yne 14 (allenylalkyne) in good yield with catalysis by Pd(0) and Cul[5], The reaction can be explained by the transmetallation of the (7-allenylpailadium methoxide 4 with copper acetylides to form the allenyKalk-ynyl)palladium 13, which undergoes reductive elimination to form the allenyl alkyne 14. In addition to propargylic carbonates, propargylic chlorides and acetates (in the presence of ZnCb) also react with terminal alkynes to afford allenylalkynes[6], Allenylalkynes are prepared by the reaction of the alkynyl-oxiranes 15 with zinc acetylides[7]. 

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. 

The intramolecular cycloaddition of munchnone intermediates (derived from the cyclodehydration of A-acyl amino acids) with 1,3-dipolarophiles was employed to construct the mitomycin skeleton. Thus, heating alkynyl acids 23 with acetic anhydride forms the intermediates 24 which undergo cyclization with loss of carbon dioxide to afford the 4-oxo-tetrahydroindoles 25 <96TL2887>... 

Wang et al. reported that FeCls- and FeBrs-promoted cyclization/halogenation of alkynyl diethyl acetals formed ( )-2-(l-halobenzylidene or alkylidene)-substi-tuted five-membered carbo- and heterocycles. It was found that the 1 1 molar ratio... 

Scheme 29 Iron-promoted cyclization/halogenation of alkynyl diethyl acetals...

R = alkyl, alkenyl, alkynyl, aryl, acetate, ester, benzyl or silyl ether groups Scheme 6.15 Cleavage of methoxyphenyl methyl (MPM) ethers using clayan. 

The C-H insertion of acetals generates protected forms of /3-ketoesters, as illustrated in Equation (22).83 Effective reactions were possible with aryl, vinyl, and alkynyl ketals, but ketals of saturated aldehydes were not viable substrates. 

Iwasawa and co-workers developed a facile method for the construction of polycyclic indole derivatives 190a and 190b by the tungsten(0)-catalyzed reaction of A-(2-(l-alkynyl)phenyl)imine 188 with the electron-rich alkenes 189a and 189b (Scheme 32).42b Photoirradiation of a mixture of imine 188 and ketene silyl acetal 189a with 10mol% of... 

Alkynyllead triacetates.1 Pb(OAc)4 reacts with a 1-alkynyltrimethyltin to form trimethyltin acetate and an unstable 1-alkynyllead triacetate (a), which can effect alkynylation of (i-dicarbonyl compounds and nitronates. In general yields are highest with R = QH, and lowest with R = H. 

Alkynylation of halo acetals. In the presence of ZnCl2 (2 equiv.) the organotin acetylide 1 couples with chloromethyl methyl ether or chloromethyl methyl sulfide to form alkynyl ethers or sulfides, respectively (equation I). 

Anomeric acetates 104 have been also used as electrophiles toward alkynylindium reagents 105 under Barbier conditions. Good yields and 1,2-cA-stereoselectivities were observed during the reaction (Scheme 36). The alkynylation was applied to the synthesis of an a-(l —>6)-C -disaccharide (110) analogue of methyl isomaltoside.108... 

Allenyl ethers are useful key building blocks for the synthesis of a-methylene-y-butyrolactones [129, 130], The synthesis of the antileukemic botryodiplodin was accomplished with the crucial steps briefly presented in Scheme 8.56. Bromoallenyl ethers 225 were easily prepared by base-induced isomerization from the corresponding /3-bromoalkyl alkynyl ether compounds and then subjected to electrophilic bro-mination with NBS. The resulting acetals 226 were converted into 2-alkoxy-3-methy-lenetetrahydrofurans 227 by dehydrohalogenation of the alkenyl bromide unit to an alkyne and subsequent radical cyclization employing tributyltin hydride [130],... 

A number of additional methods involve the addition of alkynylsilanes to electrophiles with concomitant 1,3-isomerization to afford allenylsilanes geminally substituted with the electrophile moiety. The first of these methods employed a trimethyl-silyl-substituted propargylic silane as the alkynylsilane and various acetals as the electrophile precursors (Table 9.29) [53], The allenylsilanes are formed without contamination by alkynyl isomers. 

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