Alkynylation of aldehydes

In addition to the formation of propargyl alcohols, indium chloride catalyzed the couphng of alkynes to aldehydes to give a,/3-unsaturated carbonyl compounds in water in low yields (Eq. 4.50). °° The product may be formed via the further reaction of the propargyl alcohol. 

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Scheme 3.64 Oxazolidine disulfide ligand for alkynylations of aldehydes.

Zinc catalysts have shown a major increase in their possible applications. Some examples of catalysis using halide complexes, including immobilized catalytic systems, have been discussed in Section 6.8.8. Some areas such as asymmetric alkynylation of aldehydes have been recently reviewed.930... 

Table 8 Cp2ZrCI2/AgOTf-promoted alkynylation of aldehydes...

Other Systems In contrast to the highly successful alkynylation of imines, copper catalysts failed in the asymmetric alkynylation of aldehydes. On the other hand, the combination of various Uewis acids and chiral amines were studied extensively to... 

Alkynylation of aldehydes.3 The reaction of alkynylmetals with chiral aldehydes shows no or slight diastereoselectivity, but in the presence of TiCl4, alkyn-yltributyltin reagents react with the steroid aldehyde 1 with about 9 1 diastereoselectivity. TiCl4-catalyzed reaction of 1 with allyltrimethylsilane or allyltributyltin also shows similar and comparable diastereoselectivity. 

A C2-symmetric bisoxazolidine-zinc complex catalyses alkynylation of aldehydes, giving propargyl alcohols in high yield and ee.190... 

Indium trichloride catalytically promotes the alkynylation of aldehydes in which InCl3 plays two roles transme-tallation with tin compounds and activation of aldehydes as a Lewis acid (Equation (65)).219... 

Table 25 Alkynylation of aldehydes with alkynylstannanes. Reproduced with permission from Elsevier...

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. °... 

Alkynylzinc reagents. The direct alkynylation of aldehydes is subject to asymmetric induction in the presence of a chiral base such as (-l-)-Af-methylephedrine. Addition to the C=N bond of A-tosylimines and nitrones by this procedure is also successful. ... 

Alkynyltrichlorotin reactions. The reagents are generated from 1-alkynes by treatment with SnCU-BujN in CH2CI2. Thus alkynylation of aldehydes, acetals, and enones (1,4-mode) is achieved under mild conditions using a one-pot operation. Condensation of silyl enol ethers and ketones with 1-alkynes. Both alkylide-... 

The use of polymer-supported oxazolidine derived from (17 ,2iS)-c/s-l-amino-2-indanol for the asymmetric alkynylation of aldehyde has been reported [155]. Three chiral supported-oxazolidines 244 were prepared in two steps from Merrifield resin (2.5 mmol Cl/g) (Scheme 98). 

A metal/organocatalytic direct alkynylation of aldehydes employs copper(I) t-butoxide in t-butanol, together with a prolinol bearing a pendant triphenylphosphine. ° Yields and ee of up to 98/94% are rationalized in terms of copper chelation of organocatalyst (at N, O and P) and alkyne, further organized by 0-H---0 and sp -C-H- -O hydrogen bonds, the latter being unusual in alcoholic solvent, but they are supported by QM calculations. 

Use as a Dual Catalyst in Addition of Alkynylzinc Species to Aldehydes. A dual Lewis acid/base system was reported involving NMI, Ti(OiPr)4, and (/f)-BINOL in the enantioselective alkynylation of aldehydes with diethylzinc at room temperature. Other methods to access these products have been hindered by the need for higher temperatures to generate the alkynylzinc species. A variety of propargy lie alcohols could be prepared from aromatic aldehydes in high yields and with excellent enantioselectivities (eq42). ... 

R = Aryl or t-butyl Fig. 8.20 ln(OAc)3-RuCl3 catalyzed alkynylation of aldehydes. 

A recent work by Ohshima and Shibasaki et al. revealed the dual activation capability of InBrs or In(OTf)3 catalysts in the alkynylation of aldehydes [42] (Figure 8.21). These In(III) compounds were found not only to activate the hard electrophilic carbonyl functionality, but also to activate the soft nucleophilic alkyne for the base abstraction of the terminal H, using only mildly basic amines as bases. This effectively dispenses with the need for Ru catalyst as described in the preceding paragraph. The authors found that InBr3 was appropriate for aromatic aldehydes and aliphatic aldehydes, but the use of In(OTf)3 was necessary for ketones. 

A simpler preparation of catalytic chiral indium complex based on BINOL ligand were reported by Shibasaki et al. in their asymmetric alkynylation of aldehydes [317]. InBrs was the Lewis acid of choice and the authors proposed a dual role for this bifunctional catalyst, both in activating the alkyne triple bond and the carbonyl moiety. These characteristics, and the inclusion of the chiral BINOL ligand into the In(III) center, had allowed the asymmetric addition of terminal alkynes to aldehydes with just the addition of a mild amine base (Figure 8.150). Positive nonlinear effect was observed with BINOL of varying optical enrichment, and thus the active catalytic species was expected by the authors to be most likely bimetallic in nature. 

SCHEME 12.29. The first example of a chromium-catalyzed asymmetric alkynylation of aldehydes using 1-iodo- and 1-bromoalkynes in the presence of complex 28. 

Usanov D, Yamamoto H. Enantioselective alkynylation of aldehydes with 1-haloalkynes catalyzed by tethered bis(8-qui-nolinato) chromium complex. J. Am. Chem. Soc. 2011 133 1286-1289. 

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