Cyclopentane Construction by Rh-Catalyzed Intramolecular C−H Insertion:  Relative Reactivity of a Range of Catalysts

Abstract

The preparation and Rh-mediated cyclization of the alpha-diazoester 1 are outlined, and its utility in determining the elements that contribute to the reactivity of the intermediate Rh-carbenoid is presented. The rate of disappearance of diazo ester 1 catalyzed by several representative Rh(II) complexes was determined. The observed relative rate constants for the reaction of the Rh(II) complexes with 1 varied over a range of >10(7). The reactivity of the Rh-carbenoid intermediate was explored using the ratio of the sum of (3 + 4 + 5) to 2 (cyclization vs elimination), the ratio of 3 to the sum of (4 + 5) (chemoselectivity), and the ratio of 4 to 5 (diastereoselectivity). It is striking that these four measures of reactivity were found to be independent of each other.

Asymmetric Synthesis through C–H Activation

“…A major problem in the formation of cyclopentanes via intramolecular C -H insertions of α -diazoesters is the competing β -elimination to form cis -alkenes [160] . Taber and Joshi reported that the ratio of C -H insertion versus β -elimination in such systems is infl uenced by the electronic nature of the catalyst as well as the steric bulk of the ligands [161] . Based on this work, signifi cant progress in the area was reported by Hashimoto and coworkers (Scheme 4.6 ) [160] .…”

One‐Pot Synthesis of α‐Diazo‐γ,δ‐unsaturated Esters as Versatile Building Blocks for Functionalized Dienes, Cyclopentenes, and 5,7‐Fused Bicycles

“…For instance, the 5,7-fused carbocyclic framework is found in many terpenoids of natural occurrence. [8,9] The metal-catalyzed intramolecular CÀ H insertion reaction of diazo compounds bearing aliphatic substituents is also a synthetically powerful method to regioselectively construct five-membered carbocycles, [10] such as the cyclopentane and cyclopentene motifs that are ubiquitous in a large number of natural products and advanced synthetic intermediates. [11] The reactivity of α-diazo carbonyl reactions is influenced by electronic and steric effects originating from the substitution pattern of the diazo moiety as well as the nature of the catalyst (metal and ligands).…”

“…In particular, the α-diazo carbonyl compounds bearing a hydrogen atom bonded to a β-carbon are prone to undergo β-hydride migration leading to α,β-unsaturated carbonyl compounds, rather than performing typical diazo transformations, such as the Buchner or CÀ H insertion reactions. [10,13] Although βhydride migration has been frequently regarded as a competing side reaction, this transformation is useful in organic synthesis as an efficient method to obtain substituted olefins with either (E)-or (Z)-stereoselectivity. [14] Due to the wide application of α-diazo carbonyl compounds in synthesis, many strategies for the preparation of these compounds have been developed [2] and the base-catalyzed diazo transfer reaction is one of the most widely applied.…”

Highly Enantio‐ and Diastereoselective Construction of 1,2‐Disubstituted Cyclopentane Compounds by Dirhodium(II) Tetrakis[N‐phthaloyl‐(S)‐tert‐leucinate]‐Catalyzed CH Insertion Reactions of α‐Diazo Esters

“…Taber and Joshi recently reported that the ratio of C-H insertion to β-hydride elimination products is significantly influenced by the elecronic nature and the steric bulk of the bridging ligands of dirhodium(II) catalysts. [14] 4 with an excep-tionally bulky ligand also increases the proportion of β-hydride elimination via an entropically less demand-ing pathway for steric reasons. In their studies, the find-ing that with Rh 2 (S-PTPA) 4 (3b), C-H insertion can compete effectively with β-hydride elimination is of par-ticular interest, although asymmetric induction has not been explored.…”

“…Taber and Joshi recently reported that the ratio of C À H insertion to b-hydride elimination products is significantly influenced by the electronic nature and the steric bulk of the bridging ligands of dirhodium(II) catalysts. [14] Compared with Rh 2 (O 2 CCH 3 ) 4 , which generally favors C À H insertion, the use of Rh 2 (O 2 CCF 3 ) 4 with a more electron-withdrawing ligand would generate a more electrophilic and thus more reactive rhodium(II)-carbene intermediate that would greatly favor b-hydride elimination via an early transition state, while that of Rh 2 (O 2 CCPh 3 ) 4 with an exceptionally bulky ligand also increases the proportion of b-hydride elimination via an entropically less demanding pathway for steric reasons. In their studies, the finding that with Rh 2 (S-PTPA) 4 (3b), C À H insertion can compete effectively with b-hydride elimination is of particular interest, although asymmetric induction has not been explored.…”