Ketone a, /3-acetylenic

Aldol reaction between a, -acetylenic ketones and silyl enol ethers. TrC104 is an efficient catalyst for 1,2-addition of silyl enol ethers to a,(3-acetylenic ketones.2... 

Stereoselectivity was similarly increased for additions to o, -acetylenic acids and, to a lesser extent, to a,(3-acetylenic ketones. 

Reduction of Acetylenic Ketones. The enantioselective reduction of a,3-acetylenic ketones (R-CO-CC-R, R = H or TMS) with BMS and laffords the corresponding propargylic al-coholsin good to excellent yields and >90% ee (see eq eq 4 as and example). In some cases, the reductions of more sterically... 

Brown and coworkers [1] have found that NB-Enantrane is effective only for the reduction of a,(3-acetylenic ketones. The reduction of other ketones is too slow to be of any practical use. The retarded rate is attributed to the steric bulk at the 2 position since no internal coordination has been detected by "B NMR (6 86 ppm) [2]. On the other hand, Alpine-Borane has proven to be versatile reagent for the asymmetric reduction of variety of ketones. Consequently, two reagents B-(iso-2-ethylapopinocampheyl)-9-borabicyclo[3.3.1]nonane (Eapine-Borane) and B-(iso-2- -propylapopinocampheyl)-9-BBN (Prapine-Borane) having increasing steric requirement at the 2 position, are prepared by the hydroboration [3] of 2-ethyl- and 2-n-propylapopinene. 

The high asymmetric induction achieved with Eapine-Borane for the a,p-acetylenic ketones and a-ketoesters led an examination of the reduction of a series of a,p-acetylenic ketones (Eq. 26.16) and a-ketoesters (Eq. 26.17), and the comparative reduction data of Eapine-Borane with Alpine-Borane are summarized in Tables 26.16 and 26.17. It should be mentioned that Eapine-Borane offers no advantage for the reduction of aromatic a-ketoesters. Thus, Eapine-Borane is an efficient reagent for the chiral reduction of a,(3-acetylenic ketones (Table 26.16) [1] and of alkyl a-ketoesters (Table 26.17) [1], of appreciable steric difference between the two groups on both sides of the carbonyl group. 

The rate of reduction of representative a,(3-acetylenic ketones with Prapine-Borane is slightly slower than Eapine-Borane but with improved chiral induction (Eq. 26.18 Table 26.18) [1]. 

R)-Propargylic alcohols have also been produced, this time in 73—100% e.e., by asymmetric reduction of a,/3-acetylenic ketones with the chiral borane prepared from (+)-a-pinene and 9-borabicyclo[3.3.1]nonane (9-BBN) (Scheme 10), a system already known to reduce aldehydes to chiral alcohols cf. 2,115). These results compare favourably with those from the LiAlH4- Darvon complex above, and the availability of both (+)-and (-)-o -pinene means that either (R)-or (5)-propargylic alcohols may be produced. 

Reversible interaction of the carbonyl group with an azine lone-pair (cf. 245) should facilitate substitution adjacent to the heteroatom by the anion of a )3-hydroxyethyl ketone. A similar cyclic intermediate (246) is presumably responsible for the cyclization of acetylene dicarboxylic esters with azines. Similar cyclic intermediates... 

Thus, ynaminoketones with 1,2-diaminobenzene form benzodiazepines with retention of the dialkylamino group. The reaction occurs as a nucleophilic addition in the absence of catalysts. With Q, /3-acetylenic ketones 1,2-diaminobenzene reacts in the same manner, but under proton-catalyzed conditions (72LA24). At the same time, ynamines and enynamines furnish with 1,2-diaminobenzene substituted benzimidazoles as aresultof double attack at the acetylene bond(83ZOR926 84ZOR1648). 

Analogously to ynamines and o, /3-acetylenic ketones, 4-aminobut-3-yn-2-ones react with 1,3-dipoles (68HCA443 73HCA2427 92KGS867). The reaction of 4-dimethylaminobut-3-yn-2-one with diphenylketene follows a route of [2-1-21-cycloaddition (30°C, THF, 1 h) to give 2-acetyl-3-dimethylamino-4,4-diphenyl-cyclobut-2-en-l-one (377) in 15% yield. With ethyl azidoformate (30°C, THF, 3 h), the tiiazole 378 is formed in 82% yield, whereas with phenyl isocyanate, the quinoline 379 is the product (by a [2- -4] scheme) in 70% yield (68HCA443). 

The heterogeneous catalytic system iron phthalocyanine (7) immobilized on silica and tert-butyl hydroperoxide, TBHP, has been proposed for allylic oxidation reactions (10). This catalytic system has shown good activity in the oxidation of 2,3,6-trimethylphenol for the production of 1,4-trimethylbenzoquinone (yield > 80%), a vitamin E precursor (11), and in the oxidation of alkynes and propargylic alcohols to a,p-acetylenic ketones (yields > 60%) (12). A 43% yield of 2-cyclohexen-l-one was obtained (10) over the p-oxo dimeric form of iron tetrasulfophthalocyanine (7a) immobilized on silica using TBHP as oxidant and CH3CN as solvent however, the catalyst deactivated under reaction conditions. 

Silver acetylenide 239 was found to react with aldehydes (Table 8) and the ketone in Equation (133) by using a stoichiometric amount of Cp2ZrCl2 and a catalytic amount of AgOTf at room temperature to afford the corresponding 7-hydroxy-a,/3-acetylenic esters in high yields. 

Silylphosphines add thermally to the carbon-carbon triple bond of acetylenic ketones. The reaction affords (Z)-a-silyl-/Tphosphino-a,/3-unsaturated ketones via regioselective cis- 1,2-addition (Equation (124)).286... 

Conjugate reductions. This combination (usually 1 3 ratio) effects conjugate reduction of a,p-acetylenic ketones or esters to a, 3-enones or unsaturated esters at -50° with moderate (E)-selectivity. The HMPT is believed to function as a ligand to aluminum and thus to promote hydroalumination to give a vinylaluminum intermediate, which can be trapped by an allylic bromide (equation I).1 The re-... 

In the course of a synthesis of vitamin E intermediates, a study was carried out of the reduction of a-0-acetylenic ketones with the Mosher-Yamaguchi LAH-Darvon complex, as well as with a series of new chiral 1,3-amino alcohols (103). The results of the reductions with the Mosher-Yamaguchi complex and... 

Acid-catalyzed rearrangement of tertiary a-acetylenic (terminal) alcohols, leading to the formation of a,(3-unsaturated ketones rather than the corresponding a,(3-unsaturated aldehydes. Cf. Meyer-Schuster rearrangement. 

Reduction of a,p-ynones. a,/J-Acetylenic ketones are reduced by 1 to (S> propargyl alcohols in 86-96% enantioselective purity. It is thus comparable to B-3-pinanyl-9-BBN in enantiomeric yields, although the reductions require 1-2 days and an excess of neat reagent for complete reaction. 

ASYIMETRIC REDUCTION OF a,(5-ACETYLENIC KETONES WITH B-3-PINANYL-9-B0RABICYCLO[3.3.1]NONANE (R)-(+)-1-0CTYN-3-0L... 

Af-Unsubstituted pyrazoles and indazoles add to compounds containing activated double and triple bonds (67HC 22)1,B-76MI40402>. Amongst C—C double and triple bonds, maleic anhydride, acrylic acid esters and nitriles, acetylene-carboxylic and -dicarboxylic esters (78AHC(23)263), quinones, and some a,/3-unsaturated ketones have been used with success. Phenylacetylene reacts with pyrazole in the presence of Na/HMPT as catalyst to yield the Z isomer of 1-styrylpyrazole in a highly stereoselective reaction (78JHC1543). 

BINAL-H is prepared by adding binaphlhol to a solution of LiAlH., in THF followed by one equivalent of either methanol or ethanol. The reagent generally is used in threefold excess to achieve optimal selectivities. It reduces acetylenic ketones,aromatic ketones, and a, 3-iinsaturated ketones with high optical purities. 

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