Catalyst‐Dependent Chemoselective Formal Insertion of Diazo Compounds into C−C or C−H Bonds of 1,3‐Dicarbonyl Compounds

Abstract

A catalyst‐dependent chemoselective one‐carbon insertion of diazo compounds into the C−C or C−H bonds of 1,3‐dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)−C bond of the 1,3‐dicarbonyl substrate leads to a 1,4‐dicarbonyl product containing an all‐carbon α‐quaternary center. This reaction constitutes the first example of an insertion of diazo‐derived carbenoids into acyclic C−C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C−H insertion, affording 2‐alkylated 1,3‐dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst‐dependent chemoselectivity.

Silver-Catalyzed Regio- and Stereoselective Formal Carbene Insertion into Unstrained C−C σ-Bonds of 1,3-Dicarbonyls

“…On the basis of these observations and related precedents ( Brogan and Zercher, 1996 , Liu et al., 2018 ), a plausible mechanism for this formal C−C insertion process is proposed in Scheme 4 . Initially, NaH promotes decomposition of the N -nosylhydrazone 1 to generate an unstable donor-type diazo species I , which then reacts with the silver enolate II formed from reaction of AgOTf with 1,3-dicarbonyls to give a key intermediate silver carbenoid III ( Thompson and Davies, 2007 , Caballero et al., 2011 , Luo et al., 2015 ).…”

“…In sharp contrast, the selective one-carbon insertion of diazo-derived carbenoids into unstrained acyclic C−C σ-bonds is a formidable challenge ( Brogan and Zercher, 1996 ). Very recently, we have also realized a silver-catalyzed formal carbene insertion into acyclic C-C bonds, affording 1,4-dicarbonyl products bearing an all-carbon quaternary center ( Liu et al., 2018 ). However, the process still has certain deficiencies like the need to synthesize and handle potentially toxic and explosive diazo compounds and the fact that the C-C bond cleavage is limited to 1,3-diketones.…”

“…However, the process still has certain deficiencies like the need to synthesize and handle potentially toxic and explosive diazo compounds and the fact that the C-C bond cleavage is limited to 1,3-diketones. As part of our continued interest in the silver-catalyzed activation of diazo compounds ( Liu et al., 2017a , Liu et al., 2017b , Liu et al., 2018 ), we here report the silver-catalyzed formal carbene insertion into the unstrained C−C(=O) bonds of 1,3-dicarbonyls ( Xi et al., 2014 ), using N -nosylhydrazones ( Xia and Wang, 2017 , Xiao et al., 2013 , Shao and Zhang, 2012 , Barluenga and Valdés, 2011 ) as diazo surrogates ( Figure 1 C). This represents the first example of the homologation of acyclic ketones with aryldiazomethanes ( Candeias et al., 2016 , Xia et al., 2013 ) and offers a straightforward route to construct synthetically useful polysubstituted 1,4-dicarbonyls, which can be difficult to synthesize by other approaches ( DeMartino et al., 2008 , Yoo et al., 2010 , Liu et al., 2011 ).…”

Rhodium(II)-catalyzed multicomponent assembly of α,α,α-trisubstituted esters via formal insertion of O–C(sp3)–C(sp2) into C–C bonds

“…In 2018, Bi and co-workers reported the first example that involve the formal insertion of carbenoids into acyclic C(CO)−C bonds using Ag catalyst (Fig. 1c ) 47 , 48 . Undoubtedly, the development of multiple functional groups, particularly deriving from different molecules, and insertion into unstrained C(CO)−C bonds is of great interest from both practical synthetic applications and mechanistic investigations.…”

Regio‐ and Diastereoselective Dimerization of Diazo Carbonyls: A Cooperative Catalytic Approach to Complex Scaffolds with Four Contiguous Stereocenters

“…[4] However,c arbenesa nd carbenoids also allow insertion into CÀXb onds. [5] These latter reactionsc om-monlyp roceed through the intermediate generationo fy lides. Impressive examples involve the generation of polyether macrocycles (Lacour [6] )b ut also oxyalkynylations of carbenes by hypervalent iodine reagents (Waser [7] )a nd, most recently,p hotochemically induced transformations such as fluoroetherifications or insertion reactionsi nto chalcogen-carbon bonds (Koenigs [8] ).…”