Propargylation of aldehydes

The same group also achieved the regioselective propargylation of aldehydes and ketones affording the corresponding homopropargyl alcohols (equation 5)14. 

Similarly, optically active allenyltrichlorosilanes can be prepared from 1,3-enynes and HSiCl3.109 The DMF-pro-moted propargylation of aldehydes with allenyltrichlorosilanes effects complete chirality transfer by a syn-Se process. 

Substituted prop-2-ynyl mesylates cause propargylation of aldehydes with Snl2, BU4NI, and Nal in DMI to furnish 2-substituted but-3-yn-l-ols, while 3-substituted prop-2-ynyl mesylates promote allenylation under the same conditions to produce 2-substituted buta-2,3-dien-l-ols (Equation (57)). 

Table 7 Enantioselective propargylation of aldehydes. Reproduced with permission from Elsevier...

Table 16 Indium-mediated propargylation of aldehyde with propargyl mesylate. Reproduced with permission from ACS Publications...

Allenylsilanes and -stannanes combined with a titanium salt are versatile reagents for propargylation of aldehydes (Eq. 115) [297], ketones (Eq. 116) [298], (A,0)-acetals (Eq. 117) [299], and a,/ -unsaturated ketones in a conjugate fashion (Eq. 118) [300]. Intramolecular reaction has also been reported (Eq. 119) [301] in which a Bu3Sn-carbon bond was cleaved exclusively in the presence of a TBS-carbon bond. That the isomeric starting material, propargylstannane, did not give the desired product (Eq. 120) demonstrates that the direct scission of the carbon-Sn bond by the electrophile under these reaction conditions is not a feasible path [301]. 

In general, the Lewis acid-promoted allylation and propargylation of aldehydes wifh y-substituted allylsilanes [357] and aUenylsilanes [358] are syn-selective. Information about the preferred orientation of fhe reactive double bonds in fhe transition structure is essential for rationahzing fhe stereochemistry. Denmark et al. examined the Lewis acid-promoted cychzation of fhe formyl-substituted allylsilane 119 to clarify fhe transition structure (Scheme 10.124) [359]. It was found that fhe allylation occurs from the synclinal and antiperiplanar arrangements, and the former is somewhat important. Thus, synchnal and antiperiplanar transition state models have been frequently used to explain fhe origin of the simple diastereoselection [14, 334]. 

Cuerva et developed an effleient propargylation of aldehydes and ketones using propargylic carbonates as pronucleophiles at room temperature in the presence of titanocene dichloride and palladium dichloride as catalyst system obtaining good yields and excellent regioselectivity. Oltra and... 

A catalytic stereoselective addition of aldehydes to internal alkynes (a propargylation of aldehydes) uses a simple organocatalyst and indium(III) in the presence of water. °... 

Wang, H. Jain, R. Antilla, J. C. Houk, K. N. Origins of Stereoselectivities in Chiral Rhosphoric Acid Catalyzed Allylborations and Propargylations of Aldehydes. J. Org. Chem. 2013, 78,1208-1215. 

A review describes the utility of a new class of helically chiral pyridines as asymmetric organocatalysts for propargylation of aldehydes, as well as for several other unrelated transformations. ... 

The additional a-substitution in allenylborane reagents such as 25,28, and 30 compared to 17 enhances the enantioselectivity for the propargylation of aldehydes. However, this effect is particularly apparent in their additions to /V-H aldimines, which produce homopropargylic amines in good yields (91%), but disappointing ee (from PhHC=NH, 73% ee). With 32 (325 935677-62-6 32/ 929082-37-1), the homopropargylic amine 33 is produced as essentially a single isomer (51-85%, >99 syn, 92-99% ee) (eq 13). ... 

Denmark SE, Wynn T (2001) Lewis base activation of lewis acids catalytic enantioselective allylation and propargylation of aldehydes. J Am Chem Soc 123 6199-6200... 

Denmark has also made significant contributions to the evolution of this chemistry by introducing the concept of Lewis base activation of Lewis acids. Its validity and synthetic potential were demonstrated first by achieving the highly enantiose-lective allylation and propargylation of aldehydes with 2 as an optimal catalyst as exemplified in Scheme 7.4 [5]. The key to this asymmetric catalysis is the generation of a chirally modified and activated silicon Lewis acid by the 2-promoted ionization of the weakly Lewis acidic SiCLj. 

Use of these chiral allenyl metal reagents for the introduction of a propar-gyl group allows the synthesis of all four diastereomeric permutations of dipropionate subunits. The propargyl unit also provides a convenient handle for further elaboration, as demonstrated in Marshall s synthesis of the cytotoxic polyketide discodermolide (182, Scheme 5.30) [115]. Propargylation of aldehyde 177 with an allenylzinc species derived from mesylate 172 furnishes anti product 178 in 90 10 dr. The addition of allenylstannane 180 to aldehyde 179 affords the syn product 181 in an impressive 97% yield and >95 5 dr. 

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