Propargyl aldehydes

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. 

Bohlmann (207) reported the reaction of /I -dehydroquinolizidine with methyl vinyl ketone and with propargyl aldehyde forming a partially saturated derivative of julolidine 135 and julolidine (136), respectively. Compound 135 can be prepared also by mercuric acetate dehydrogenation of ketone 137, which is formed by condensation of 1-bromoethylquinolizi-dine with ethyl acetoacetate (Scheme 11). 

This catalyst was successfully applied to the Diels-Alder reaction of propargyl aldehydes as dienophUes [12] (Scheme 1.21, Table 1.8). Though 2-hutyn-l-al and 2-oc-tyn-l-al are unreactive dienophUes, silyl- and stannyl-suhstituted a,/ -acetylenic aldehydes react with cydopentadiene readily in the presence of 20 mol% of the catalyst at low temperature to give hicyclo[2.2.1]heptadiene derivatives in high optical purity these derivatives are synthetically useful chiral building blocks. 

Cyanohydrin diethyl phosphates 87, easily accessible from propargyl aldehydes or ketones of type 86, reacted with lithium dialkylcuprates or similar reagents via an Sn2 process to give cyanoallenes in moderate to good yields [135]. The transformations 80 —> 81 and 84 —> 85 are only formally also SN2 reactions. Thus, plausible catalytic cycles, which include different short-lived palladium intermediates, have been postulated to explain these nucleophilic substitution reactions [127, 134],... 

Recently, Yamamoto and coworkers249 reported the first examples of chiral induction in the cycloadditions of cyclopentadiene to propargylic aldehydes 402 using catalysts 380c, 387 and 393 (equation 119). The cycloadditions were stated to proceed via exo transition states and were accelerated by coordination of the Lewis acid to the carbonyl group. 

Jeong and co-workers utilized a cobalt-alkyne complex to enhance enantioselectivity of the addition of bis (homoallyl)zinc to propargyl aldehydes 68 by the exaggeration of steric environment. The reaction provided optically enriched propargyl alcohol 69 in the presence of a chiral ligand and titanium tetra(isopropoxide) in excess. Adduct 69 was subjected to PKR to yield optically enriched bicyclic compounds 70 (Equation (39)). ... 

Chiralpropargylic alcohols.1 The magnesium enolate of 1 undergoes an aldol type condensation with propargylic aldehydes to form adducts (2) in 50-75% yield. These are readily reduced to (S)-propargylic alcohols (3), obtained in 70-90% ee. 

An efficient double conjugate addition of ethane and propane dithiols in the presence of sodium methoxide to propargylic carbonyl compounds (127) has been developed. The corresponding amino-substituted propargylic aldehydes afforded piperidine derivatives.182... 

Probably the most convenient laboratory preparation of isothiazole was devised by Wille and his collaborators34 (Scheme 11) and depends on the cyclization with liquid ammonia of the cis-addition product from propargyl aldehyde and sodium thiosulfate or thiocyanate.34, 35... 

A higher yield (90%) may be obtained by ring closure with potassium thiohydroxylamino-iSksulfonate (Scheme 12). The same reagent may be condensed with propargyl aldehyde to give an intermediate which forms isothiazole on treatment with alkali, possibly via a transient thiooxime derivative.36... 

Complexation of propargyl aldehydes to cobalt also enhances the reactivity and enantioselectivity of the addition of alkylzinc reagents. This fact was used to create non-racemic enyne-ol 88 reacting the aldehyde 86 with bis-homoallylzinc in the presence of a chiral frzs-(sulfonamide) and Ti(OlPr)4. The resulting complexed substrate 87 underwent the PKR promoted by TMANO in a one pot fashion (Scheme 25) [122]. 

Scheme 25 One pot asymmetric addition of dialkyl zinc to a cobalt complexed propargyl aldehyde followed by PKR...

Alkynyl ketones can be prepared using the former useful methodology. Starting from propargyl aldehyde diethyl acetals and benzotriazole under toluene reflux, l-(benzotriazol-1-yl) propargyl ethyl ethers were prepared in 83-84% yield. The deprotonation is very... 

As the steric bulk of the ring substituents is increased and their number reaches a critical level, dimerization is retarded. For example, the cycloadducts (166) of ful-vene 165 with propargylic aldehyde or methyl propiolate are reported to undergo dimerization at 20 °C, while the dimethyl acetylenedicarboxylate adduct 167is stable under these conditions.239 ... 

Alkynols complexed to cobalt can be oxidized to alkynals without decomplexation. Propargyl aldehydes are protected from polymerization upon complexation with Co2(CO)6. These aldehydes smoothly undergo Wittig-type reactions. Carbonyl-ene reactions have been demonstrated (Scheme 194). Complexation to cobalt protected the enyne in complex (132) from Michael-type reactions (Scheme 195). Alkenyl-substituted complexes undergo [3 + 2]cycloadditions with nitrile A-oxides (Scheme 196). 

Cobalt-complexed propargylic aldehydes can be alkylated using both cyclic and acyclic trimethylsilyl enol-ethers and -esters in the presence of a Lewis acid. Boron trifluoride etherate is the most frequently employed Lewis acid. 

Aldehydes are one of the most impotent synthons in organic chemistry. Many methods of preparation of formyl carboranes have been discussed previously (E. I. Rosemund method,14 Sonn-Miller reaction,14 reaction of dodecaborane with diacylal of propargyl aldehyde,14 Swem Oxidation15). Since oxazolines are rather good reagents for the preparation of aldehydes and nitriles, we developed a method of preparation of carboranyl oxazolines (Scheme 9). 

Propargylic aldehyde was also used to prepare, by condensation with (+)-(R)-7-butyl p-tolylsulfinylacetate, a precursor of the C-3-C-8 fragment of leukotriene B4 (eq 6)."... 

Conjugated yne-2-ynylidene 1,3-dithioles 228 were synthesized via Wittig reactions of phosphonium salts 225 with 3-phenyl-substituted propargyl aldehydes 227 (R = H, = Ph). Diaryl-substituted derivatives 228 were prepared in Horner-Wittig reactions of phosphonates 226 with ketones 225 (R =R = Ph or -02NC6H4) (Equation 13) <2004CL1190>. 

The dialdehyde 791 was prepared starting from the readily available 77 -CS2-iron complex 789 and propargyl aldehyde 788. Treatment of the resulting intermediate (l,3-dithiol-2-ylidene)-ionic complex 790 with iodine afforded the desired 2,6(7)-diformyl-TTF 791 (Scheme 118) <2000CEJ1199>. By analogy, tetraacetyl-TTF was also prepared using hexa-3-yne-2,5-dione <1996TL8861>. 

Bis(tributylstannyl)propenes are available from the double stannylcupration of an enone or the acetal of propargyl aldehyde.21... 

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