A, p-Acetylenic ketones

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. 

Pd-catalyzed isomerization of ynones to furans has been an active area of research over the last decade. Huang et al. described a Pd-catalyzed rearrangement of a,P-acetylenic ketones to furans in moderate yield [102], For example, Pd(dba)2 promoted the isomerization of alkyne 124 to a putative allenyl ketone intermediate 125, which subsequently cyclized to the corresponding furan 126. 

A similar substituted furan synthesis was realized via a Pd-catalyzed tandem carbonylation-arylation using an a,p-acetylenic ketone, carbon monoxide, and bromothiophene [104],... 

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 summary, a number of effective chiral reducing agents have been developed based on the modification of LAH. Excellent results have been obtained with aryl alkyl ketones and a,p-acetylenic ketones. However, dialkyl ketones are reduced in much lower enantiomeric excess. This clearly indicates that steric effects alone do not control stereoselectivity in these reductions. Systematic studies have been carried out with the objective of designing improved reagents. A better understanding of the mechanisms and knowledge of the active species is required in order to provide more accurate models of the transition states of the key reduction steps. 

Clean formation of a, p-acetylenic ketones could be achieved by carrying out the reaction with a catalytic amount of Cul in the presence of Et3N [Eq. (8.17)]124 or inducing the acylation with a Pd complex and Cul in the presence of Et2NH 125... 

Novel practical methods using various reagents, such as [Co(OAc)Br],1355 sulfur trioxide,1356 or ds-dioxoruthenium complexes,1357 were developed to transform alkynes to 1,2-diketones. Radical-catalyzed aerobic oxidation using A-hydro-xyphthalimide combined with a transition metal (Co, Cu, or Mn) affords a,P-acetylenic ketones in good yields.1358 Oxidation by the HOF. acetonitrile complex yields diketones, ketoepoxides, or cleavage products.1359 Ozonolysis of acetylenes combined with trapping techniques affords to isolate various derivatives.1360,1361 New information for the ozonolysis of acetylene was acquired by quantum-chemical investigatons.1362... 

Matsumara K, Shohei H et al (1997) Asymmetric transfer hydrogenation of a,P-acetylenic ketones. J Am Chem Soc 119 8738-8739... 

The a,p-acetylenic ketones can be synthesized in good yields by the selective mono-hydroboration-oxidation process of conjugated diynes. The monohydroboration of conjugated diynes with disiamylborane places boron preferentially at the internal triple position of the diyne system. The resultant organoboranes on treatment with sodium hydroxide and 30% H202 afforded the a,P-acetylenic ketones (Eq. 33) 79). 

A more general method for the synthesis of a,P-acetylenic ketones has been recently reported, and is indicated in Eq. 34 80). 

Midland, M. M., McDowell, D. C., Hatch, R. L., Tramontane, A. Reduction of a,P-acetylenic ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane. High asymmetric induction in aliphatic systems. J. Am. Chem. Soc. 1980,102, 867-869. 

The selective reduction of the a,p-acetylenic ketones such as 4.12 to a,p-ethylenic ketones is accomplished by reaction with DIBAH in THF-HMPA [TY2]. In the presence of a catalytic quantity of MeCu, the reduction is faster and the stereoselectivity is modified (Figure 4.4). Nevertheless, the stereoselectivity is never very high [TY2]. The reagent does not reduce the isolated triple bond of 4.13 (Figure 4.4). 

Asymmetric transfer hydrogenation of a,p-acetylenic ketones with a pre-existing stereogenic center affords diastereomeric propargylic alcohols [128]. For example, reduction of a chiral amino ketone (S)-48 with R,R)-42 in 2-propanol gives (3S,4S)-49 predominantly (Scheme 42), whereas reaction using (S,S)-42 affords the 3R,4S stereoisomer in >97% yield. The sense of diastereoface selection is mostly dependent on the chirality of the Ru catalyst. 

Prior to this work, Mosner and Yamaguchi" reported similar reduction with an LAH-quinine combination however, no example of acetylenic ketone was attempted. In a later study, Midland et al. developed a-pinene-9-Borabicyclo [3.3.1] nonane complex as an excellent reagent for the reduction of a,P-acetylenic ketones and observed high asymmetric induction in aliphatic systems (Table 21.1). 

Based on this strategy, Garcia et al. have used oxazaborolidine, (R)-2, and effectively reduced several a,p-acetylenic ketones. The e.e. value of the products was in the range 90 to 97%. To improve the results further, the monobranched ketones were complexed with hexacarbonyl dicobalt complexes and snbjected to reduction. Unfortunately, the reactions were sluggish and under forced conditions or modifications of oxazaborolidine resnlled only in low yields and enantioselectives (Table 21.3). 

In a continuation of this work, the authors investigated the reaction between a,p-acetylenic ketones and aromatic aldehydes in the presence of TiCl4 or TiBr4 to provide the desired p-halo MBH adducts 243 (Scheme 2.142) (similar to those obtained by Kataoka). Similar results were obtained by employing a... 

The reduction of a,p-acetylenic ketones is accomplished in 24-48 h at room temperature by using twofold excess of NB-Enantrane and running the reaction without solvent. Both chemical and enantiomeric yields are high (Table 26.14) and provide (S)-propargyl alcohols. The reduction fits the steric model proposed for Alpine-Borane reduction [3]. Nopol benzyl ether liberated after the reduction maybe easily isolated during purification of the product and recycled. 

Table 26.14 Reduction of a,p-acetylenic ketones with NB-Enantrane [1] ...

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. 

Oxidation of Alkynes to a, P-Acetylenic Ketones. Various alkynes have been converted to the corresponding a./S-acetylenic ketones by oxidation with oxygen and r-BuOOH using copper(II) chloride as the catalyst (eq 33)7 The catalytic system gives both high conversion and selectivity in the formation of the a,p-acetylenic ketones. This selectivity results fromrapid oxidation of the intermediate acetylenic alcohol, RC=CCH(OH)R, to ketone under the reaction conditions. The resulting acetylenic ketone is deactivated from further oxidation. 

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