Of a,P-acetylenic ketones

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. 

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-... 

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... 

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

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. 

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). 

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. 

Hussain, S. and Agosta, W. C., Photochemical [3-1-2]-cycloaddition of a,P-acetylenic ketones with simple olefins. Tetrahedron, yj, 3301, 1981. 

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