A,p-ynones

Table 5.6. Pd-catalyzed reactions of a,p-ynones with saturated acylzirconocene chlorides.

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. 

Hydrogenation of an a,P-ynone, 3-decyn-2-one (14), to the corresponding cA-enone was successful withPd-CaC03 as catalyst (eq. 4.17).52 It was necessary to use a rather... 

A new approach for the synthesis of functionalized 4-alkylquinolines was developed utilizing electrogenerated carbanions <07SL1031>. The desired 4-alkylquinolines 83 were synthesized through a sequential alkylation/heterocyclization of p-(2-aminophenyl)-a,p-ynones 84 and the electrogenerated carbanions of nitroalkanes 85. This novel approach avoided metal and base catalysts and is performed under solvent free conditions. 

The Corey-Bakshi-Shibata reduction (CBS reduction) is a highly enantioselective method for arylketones, diaryl ketones, and dialkylketones. In addition, cyclic a,p-unsaturated ketones, acyclic a,p-unsaturated ketones, and a,p-ynones are reduced enantioselectively in a 1,2-fashion. The high enantioselective nature of this reduction relies on the chiral oxazaborolidine catalyst, shown in the reaction scheme, in the presence of borane or a dialkylborane. Reviews (a) Singh, V. K. Synthesis 1992, 605-617. (b) Deloux, L. Srebnik M. Chem. Rev. 1993,93,163-1. (c) Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37. 1986-2012. 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,P-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

Hydroboration of the C-C unsaturated bond may be a possible side reaction in the reduction of a,P-unsatuxated ketones. However, in many cases, some ox-azaborolidines successfully catalyze the selective reduction of ketone carbonyls (Scheme 6). The borane reduction of 2-methylnon-l-en-3-one with oxazaborolidine 45 showed a clean conversion to the allylic alcohol (98%, 92% ee S) [82]. The same catalyst [83] and 4b [84] were effective for the reduction of a,P-ynones [83]. 

Supported phosphine 54 also acts as an efficient catalyst for isomerization processes. The isomerization of nitroolefins to obtain the (Ej-isomer has been reported to occur in quantitative yields and without the activation of other side reactions [196]. Similarly, the isomerization of a,P-ynones to (/ , fP-y,8-dieriories (60) is catalyzed by 54 with high efficiency and stereoselectivity (Scheme 10.12) [197]. The recovery and reuse of these catalysts is generally reported, but this is strongly limited, as in many other applications involving phosphines, by their oxidative degradation. 

Helal CJ, Magriotis PA, Corey EJ (1996) Direct Catalytic Enantioselective Reduction of Achiral a,p>-Ynones. Strong Remote Steric Effects Across the C-C Triple Bond. J Am Chem Soc 118 10938... 

P-carbohnes [29] (Schane 3, equation 1). A variety of secondary amines were employed, and the method was adapted to the preparation of pyrrolo[3,2-/lindoles and dipyrrolo[3,2-h 2, 3 -c]pyridines [30]. Cacchi and colleagues synthesized 3-aroylindoles from the copper-catalyzed cyclization of lV-(2-iodoaryl)enaminones (equation 2) [31]. The latter were prepared from 2-haloanilines and a,p-ynones, which can react directly with 2-iodoaniline under the copper protocol to give 3-benzoyl-2-phenylindole (76%), thus bypassing the enaminone. Patel described a copper-catalyzed 3-aroylindole synthesis from 2-alkynylated... 

I 7 7 Oxazaborolidines as Asymmetric Inducers for the Reduction of Ketones and Ketimines Table 11.8 Reduction of a,p-ynones. 

Scheme11.11 Remote steric effect of substrate and 6-substituent on enantioselection in the 2-catalyzed reduction of an a,P-ynone.

Alternatively, a double intramolecular hetero-Michael addition (DIHMA) can be used to assemble a spiroacetal from an a,p-ynone (Scheme 61). NMR smdies have shown that, in accordance with Baldwin s rules, initial 6-endo-dig cyclization rather than 6-exo-dig is favored. Subsequent 5-exo-trig cyclization furnishes the 5,6-spiroacetal [132]. The corresponding 6,6-spiroacetals are obtained in an analogous manner. 

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