A survey of enoldiazo nucleophilicity in selective C–C bond forming reactions for the synthesis of natural product-like frameworks

Abstract

A survey of in situ, catalytically generated carbocations for coupling with enoldiazoacetate nucleophiles was performed. These couplings facilitate the rapid assembly of complex organodiazo compounds that provide a template for the synthesis of a variety of carbocyclic and heterocyclic ring systems.

Iridium‐Catalyzed Enantioselective C(sp3)–H Borylation of Cyclobutanes

“…[3] Thus, the stereo-controlled synthesis of cyclobutanes has received a great deal of interest. Examples of [2+2] cycloaddition, [4] ring expansion of cyclopropanes [5] and intramolecular ring closure of linear substrates [6] provide efficient routes to access chiral cyclobutanes. Another attractive alternative is the asymmetric post-functionalization of prochiral cyclobutane derivatives, usually accomplished by α-functionalization of cyclobutanones, [7] conjugate addition of cyclobutenones, [8] allylic alkylation of cyclobutenecarboxylic acid esters [9] and C-H functionalization [10] of cyclobutanecarboxamides.…”

Catalytic Divergent [3+3]‐ and [3+2]‐Cycloaddition by Discrimination Between Diazo Compounds

“…[5a] In these chemical processes,e ach diazo compound has af unctional role in product formation. [8] Additionally, a-diazocarboximides are recognized precursors to cyclic carbonyl ylides that readily undergo 1,3-dipolar cycloaddition reactions. These extraordinarily efficient, highly selective cycloadditions furnish unique multicyclicazepine,pyrrolizine and oxazole derivatives that are important skeletons in many biologically active natural products and pharmaceuticals.…”

“…[6] Enoldiazoacetates 1 are efficient precursors of metalloenolcarbenes,whose carbons 2and 4are electrophilic centers and undergo stepwise [3+ +n]-cycloaddition reactions via initial nucleophilic addition; [7] in contrast, carbons 2a nd 4o ft he precursor enoldiazo compounds are nucleophilic centers that are able to react with electrophiles. [8] Additionally, a-diazocarboximides are recognized precursors to cyclic carbonyl ylides that readily undergo 1,3-dipolar cycloaddition reactions. [9] We envisioned cross-coupling reactions between the enoldiazoacetate,a sthe dipolarophile,a nd cyclic carbonyl ylides formed from a-diazocarboximides.O ur inquiry began with the reaction of readily accessible triisopropylsilyl (TIPS)-substituted enoldiazoacetate 1a and N-diazoacetyl-2-pyrrolidinone 2a in the presence of 5mol %o fC u-(CH 3 CN) 4 BF 4 at room temperature in dichloromethane.…”

An efficient route to highly enantioenriched tetrahydroazulenes and β-tetralones by desymmetrization reactions of δ,δ-diaryldiazoaceto-acetates

“…We have recently been able to access d,d-diaryl-a-diazo-bketoesters (1) by a simple one-step Lewis acid catalysed reaction between enoldiazoacetates and benzhydryl acetates. 7 These products are suitably constructed for benzylic insertion, aromatic substitution, or aromatic cycloaddition (Buchner reaction). 1a Since initial reactions with rhodium acetate showed preference for aromatic cycloaddition (Scheme 1), we considered whether chiral catalysts could achieve highly enantioselective reactions.…”

“…Reaction of methyl 2-diazo-3-oxo-5,5-diphenylpentanoate 1a (Ar = Ph, R = Me) with Rh 2 (OAc) 4 in refluxing CH 2 Cl 2 gave a mixture of aromatic cycloaddition (2a) and substitution (3a) products in a 4 : 1 ratio that, following treatment with TFA, formed only the substitution product. 7 The initially formed substitution product could have arisen by either electrophilic aromatic substitution of the intermediate metal carbene or by rearrangement of 2a following aromatic cycloaddition with Rh 2 (OAc) 4 acting as a Lewis acid to catalyze the transformation to 3a from 2a.…”