Reduction alkynyl ketones

Treatment of 210 under traditional Eschenmoser fragmentation conditions gave only low yields of the desired alkynyl ketone 211, but this result was improved significantly by use of p-nitrobenzenesulfonylhydrazine in place of the commonly used p- lolueriesul fonylhydrazine. Compound 211 was transformed into the bis-oxime 212, reductive cyclization of which by treatment with ZrCU and NaBH4 and subsequent acylation afforded the polycyclic compound 213 with the desired all-cis... 

Recently, the silane-mediated reductive cyclization of activated alkynes with tethered ketones using Stryker s reagent as a catalyst was reported.112,90b Alkynyl ketone substrate 84a was treated with a catalytic amount of Stryker s reagent in the presence of polymethylhydrosiloxane (PMHS) to afford the cA-fused hydrindane 84b as a single diastereomer. This method is applicable to both five- and six-membered ring formation, but often suffers from competitive over-reduction of the reaction products (Scheme 59). 

Asymmetric reduction of Myny ketones. The (Reform of the complex (1) reduces alkynyl ketones to optically active propargylic alcohols (usually R) in 65-85% chemical yield and in 85-95% optical yield use of the (S)-form of 1, as expected, results in the epimeric alcohol. This reduction was used in a synthesis of the natural Japanese beetle pheromone (2, equation I).1... 

Conversion ofpropargyl esters to dihydrofurans1 (11,469-470). The reaction can be used for an enantioselective synthesis of dihydrofurans. Thus reduction of 3-hydroxy-l-alkynyl ketones (2) with Midland s reagent, (+)-l, provides (4S)-2-bu-tyne-l,4-diols (3) in 84-91% ee. Monoacylation (4) followed by treatment with... 

Cycloadditiom. This reaction provides an enantioselective synthesis of a cyclooctane-containing terpenoid (5). The optically active precursor (3) was obtained by reduction of the r-alkyl alkynyl ketone 1 with lithium aluminum hydride... 

Noyori et al. demonstrated the effectiveness of the BINAL-H reduction method by synthesizing the Japanese beetle pheromone (R)-167 (Scheme 4.3f). The alkynyl ketone 17 was treated with 3 equivalents of (Wj-IJINAL-H at —100 C for 1 hour and then held at —78 C for 2 hours. The propargylic alcohol 18 was obtained in good yield and with moderate enantioselectivity of 84% ee. Exposure... 

The CBS reduction has also proven to be an efficient method for asymmetric reduction of a,ft-unsaturated enones14 and ynones15 (Scheme 4.31). The asymmetric reduction of alkynyl ketones affords propargylic alcohols 30 with high levels of enantioselectivity and in moderate to good yields. Optimized reaction conditions for the reduction are the use of THF at — 30° C, 2 equivalents of chiral oxazaborolidine 28b, and 5 equivalents of borane methyl sulfide complex. 

Midland and others reported that B-isopinocampheyl-9-borabicyclo[3.3.l]no-nane [Alpine-Borane (7 )-79] is an effective reagent for the highly asymmetric reduction of alkynyl ketones to afford the propargylic alcohol 8030 (Scheme 4.3z). The reagent (R)-19 is prepared from (+)-a-pinene and 9-borabicyclo[3.3.1]no-nane (9-BBN) and often represented as 19banana. The levels of asymmetric... 

Reductive cyclization. Potassium in liquid ammonia is an effective reagent for reductive cyclization of 5-alkynyl ketones. This reaction provides an efficient route to the D ring of gibberellic acid (1 —> 2). Sodium naphthalenide has been employed in a similar fashion for the preparation of 2-methylenecyclopentanols and 2-giethyl-enecyclohexanols (3 — 4). ... 

Asymmetric Reductions. NB-Enantrane is an analog of B-3-Pinanyl-9-borabicyclo[3.3.1 Jnonane (Alpine-Borane ). Since the absolute configuration of nopol is the opposite of (+)-a-pinene, the reagent provides the opposite mode of asymmetric induction. The reagent provides higher asymmetric induction than Alpine-Borane for cases where the two groups flanking the ketone are relatively small, such as methyl or ethyl alkynyl ketones (eq 2). 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

Vigneron and co-workers have observed that a complex of LAH, (—)-(ll), and DMP (1 1 2), in ether at — 15°C, appears to show the highest enantioselectivity in the reduction of a series of aromatic and alkynyl ketones to the corresponding (R)-alcohols (Figure 3). Interestingly, the optical purities of the products obtained were lower both at higher and lower reaction temperatures. 

Table 3. Asymmetric Induction in the Reduction of Alkyl Alkynyl Ketones...

Table 4. Reduction of a-Alkynyl Ketones by Tris[(A )-2-methylbutyl]aluminum (lib )102...

ASYMMETRIC REDUCTION OF PROCHIRAL a, P-ALKYNYL KETONES TABLE 21.1 a-Pinene-9-BBN Complex... 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

A well-established preparative method of alkynyl ketones 110 is the Sonogashira-type carbonylation of aryl halides in the presence of terminal alkynes. (Trimethylsi-lyOpyridylethyne (111), deprotected in situ, reacted with 3-iodotoluene and CO to give the alkynyl m-tolyl ketone 112 using DPPF as a hgand. Pd-catalyzed reductive cyclization of 112 using HCO2H afforded the 1,8-naphthyridine 113 [48]. 

For the final part (Scheme 5.3), the 20-carbon chain of fumonisin Bj was coupled from the Uthium acetylide derived from 273 and the Weinreb amide 279 (233). After enantioselective reduction of the alkynyl ketone 281 (234, 235), the C-10 stereochemistiy was set, followed by benzyl ether formation and acid-catalyzed acetonide removal, to provide diol 282 (236). Using tricarballylic acid dibenzyl ester, the two hydroxy groups were esterified (237) and the hydrogenation of the azide, the alkyne, and the benzylic ethers led to the target product, fumonisin Bj (249). The spectroscopic analysis matched with those of commercial fumonisin Bj and further experiments on the synthetic material showed inhibitoiy activity on sphingoUpid biosynthesis. 

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