Alkynyl aluminum reagents

The binaphthol-modified lithium aluminum hydride reagents (BINAL-Hs) are also effective in enantioselective reduction of a variety of alkynyl and alkenyl ketones2 (Scheme 4.3b). When the reaction is carried out with 3 equivalents of (S)-BINAL-H at —100 to —78 C, the corresponding propargylic alcohol 3 and allylic alcohol 4 are obtained in high chemical yields with good to excellent levels of enantioselectivity. As is the case with aryl alkyl ketones, the alcohols with (.V)-con figuration are obtained when (S)-BINAL-H is employed. 

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. 

One of the severest challenges of asymmetric synthesis is the direct enantioselective construction of quaternary stereogenic centers. Brian Pagenkopof of the University of Texas has reported (Chem. Communications 2003 2592) that alkynyl aluminum reagents will open a trisubstituted epoxide such as 10 at the more substituted center, with inversion of absolute configuration. As the epoxide 10 is available in high from 9 by the method of Yian Shi of Colorado State (J. Am. Chem. Soc. 119 11224, 1997), this opens a direct route to quaternary cyclic stereogenic centers. 

Aldehydes and ketones have also been prepared by nucleophilic cleavage of resin-bound O-alkyl hydroxamic acids (Weinreb amides [744]) with lithium aluminum hydride [745] or Grignard reagents (Entries 1 and 2, Table 3.41). Similarly, support-bound thiol esters can be cleaved with Grignard reagents to yield ketones [272], or with reducing agents to yield aldehydes (Entry 3, Table 3.41). Polystyrene-bound sele-nol esters (RCO-Se-Pol) react with alkynyl cuprates to yield alkynyl ketones [746]. 

The requisite (propargyloxy)aluminum reagents 25 are readily accessible from either (i) (o,o -biphenylenedioxy)methylaluminum (26a) and the corresponding pro-pargylic alcohols 27 or (ii) (o,o -biphenylenedioxy)(t-butoxy)aluminum (26b) and 27 by ligand exchange. The second preparative method also works well and gives results comparable with those from the first method in the MPV alkynylation of various reactive aldehydes (Sch. 12). 

Since hydroalumination by neutral aluminum hydrides is an electrophilic attack on a C= or C=C linkage, the reaction can be accelerated by Lewis acids such as aluminum halides, and be retarded by Lewis bases like R3N, R2O or even unsaturated R3AI cf. equation 38). Such reagents also exert an effect on the syn or anti character of the A1—H adduct. Evidence suggests that Lewis acids or bases principally affect the rate of isomerization of the initial syn adduct into the generally more stable anti adduct Lewis bases retard such isomerizations, while Lewis acids promote them. The presence of ethers or tertiary amines stabilize the syn adducts of alkynyl-silanes and -germanes (47) and permit such adducts to be formed in >95% geometrical purity (Scheme 12). ... 

The palladium-catalyzed systems seem quite flexible with regard to the nature of the organoaluminum, since aJkyl-, alkenyl- and alkynyl-aluminum reagents were used successfully (entries 8-14, Table 18). Furthermore, the acyl chloride substrates include alkyl, aryl and alkenyl substituents. 

In addition to their reactions with trlmethylsilyl enol ethers, (propargyl1um)Co2(C0)g complexes react with a variety of other mild carbon nucleophiles including activated aromatic compounds, g-dicarbonyl compounds, other enol derivatives (enol acetates and ketones directly), allylsilanes, and alkyl- and alkynyl-aluminum reagents. These reactions provide a flexible means to introduce the synthetically versatile propargyl function. Key features of propargylations using these complexes are 1) ready... 

No general method is available for tert-alkyl-alkynyl-coupling based on sodium or lithium alkynylide reagents because of prevalent elimination. However, trialkyn-ylalanes obtained from the corresponding alkynyllithiums and anhydrous aluminum trichloride undergo clean reaction with tert-halides to produce rert-alkyl substituted... 

Control of S 2 versus S(j2 additions to vinyl epoxides continues to be of interest. The usual group of alkynyl lithium reagents generally provided a mixture of the S 2 and 8 2 products <05EJO3946>. However when lithio-ethoxyacetylene was used, the 8 2 product 68 was the major product (98 2). Changing the metal to aluminum provided a shift to the 8 2 product 69 in a similar 98 2 ratio as a mixture of E and Z-isomers. 

Alkynylation of enones. The nickel catalyst obtained from Ni(acac)2 and DIBAH catalyzes the conjugate addition of organoaluminum acetylides even to transoid enones. The acetylenic aluminum reagent is prepared according to Fried s procedure (4, 144) from a lithium acetylide and dimethylaluminum chloride. In all cases only 1,4-addition is observed. -Examples ... 

The scope of nitriles for the carbocyanation reaction of alkynes can be expanded by cooperative nickel/Lewis acid catalysis. Alkenyl [80, 81] and alkynyl cyanides [83, 84] also participate in the addition reaction to give highly conjugated nitrile products by nickel/BPh3 catalysis (Scheme 27). The use of aluminum-based Lewis acids causes isomerization of the double bond of alkenylcyanation products, whereas alkynylcyanation is sluggish with the aluminum reagents. 

Micouin et al. found that the nucleophilic substitution of bicycUc hydrazine-epoxide 7 using alkynylaluminum reagent led to the formation of hydroxy group-rearranged product 8 (Scheme 6) [20]. The plausible mechanism of this unique reaction involves (1) the initial formation of aziridinium cation intermediate catalyzed by aluminum Lewis acid and (2) the intramolecular nucleophilic migration of alkynyl group, as in transition state 9. 

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