Highly Enantioselective Cyclopropenation Reaction of 1‐Alkynes with α‐Alkyl‐α‐Diazoesters Catalyzed by Dirhodium(II) Carboxylates

Abstract

As a result of enormous ring strain, cyclopropene compounds display a range of diverse reactivities in both noncatalytic and transition-metal-catalyzed transformations, thus presenting unique opportunities for organic synthesis. [1,2] To further enhance the synthetic potential of cyclopropenes, the development of expeditious methods for the synthesis of enantioenriched cyclopropenes is highly desirable.[3] In this context, a cyclopropenation reaction of alkynes with diazo compounds that is catalyzed by chiral dirhodium(II) complexes represents one of the most powerful means for the construction of this class of optically active building blocks. Doyle, Müller, and co-workers were the first to demonstrate asymmetric induction (up to ! 98 % ee) in cyclopropenation reactions of terminal alkynes including propargyl alcohol or propargylamine derivatives with diazoacetates using [Rh 2 (5S-mepy) 4 ] (2 a; Scheme 1) as a chiral catalyst.[4] Doyle et al. also reported an enantioselective intramolecular cyclopropenation of diazoacetates, in which [Rh 2 (4S-ibaz) 4 ] (2 b) provided macrocyclic cyclopropenes in up to ! 99 % ee.[5] Corey and coworkers demonstrated that a new mixed carboxylate/carboxamidate catalyst [Rh 2 (OAc)(dpti) 3 ] (3) is highly exceptional for cyclopropenation of a broad range of terminal alkynes with ethyl diazoacetate.[6] The extension of this methodology to include a-substituted a-diazoacetates is particularly attractive because it has the capability to form cyclopropenes with a quaternary stereogenic carbon center. [7][8][9] Although high levels of enantioselectivity (up to 99 % ee) in cyclopropenations of terminal alkynes with aryldiazoacetates [7a] or arylvinyldiazoacetates [7b] under catalysis by [Rh 2 (S-dosp) 4 ] (4) have been reported by Davies and co-workers, the goal for the reaction with a-alkyl-a-diazoesters remains elusive because of the propensity to form a,b-unsaturated esters through a 1,2-hydride shift.[10] Panne and Fox recently disclosed that dirhodium(II) tetrapivalate exhibits high selectivity for cyclopropenation over alkene formation in the reaction of terminal alkynes with a-alkyl-a-diazoesters. [11,12] However, to the best of our knowledge, an enantioselective version of this reaction has not been reported.Our research group has previously demonstrated the first examples of highly enantio-, diastereo-, and chemoselective intramolecular C À H insertion reactions of a-alkyl-a-diazoesters by using dirhodium(II) tetrakis[N-phthaloyl-(S)-tertleucinate] ([Rh 2 (S-pttl) 4 ], 1 a) in which high levels of asymmetric induction (up to 95 % ee) were achieved. [13][14][15] Herein, we report that [Rh 2 (S-tbpttl) 4 ] (1 f), a new dirhodium(II) carboxylate complex that incorporates N-tetrabromophthaloyl-(S)-tert-leucinate as chiral bridging ligands, catalyzes the cyclopropenation reaction of terminal alkynes with 2,4-dimethyl-3-pentyl a-alkyl-a-diazoacetates to give 1,2-disubstituted 2-cyclopropenecarboxylates in good to high yields and with up to 99 % ee. Scheme 1. Chiral dirhodium(II) com...

Chiral Dirhodium Catalysts: A New Era for Asymmetric Catalysis

“…They reported that [Rh 2 (S-topttl) 4 ], a new dirhodium(II) carboxylate complex that incorporates Ntetrabromophthaloyl-(S)-tert-leucinate as chiral bridging ligands, catalyzes the cyclopropanation reaction of terminal alkynes with 2,4-dimethyl-3-pentyl--alkyl--diazoacetates to give 1,2-disubstituted 2-cyclo-propenecarboxylates in good to high yields and with up to 99% ee [144] (Scheme 8).…”

“…Hashimoto and coworkers [50], in 2008 disclosed the first example for the enantioselective amination for an allylic C-H bond of silyl enol ethers 212 derived from cyclic ketones 211 or enones of six-membered-rings by using [(2-nitrophenylsulfonyl)imino]phenyliodinane (213; NsN=IPh) as a nitrogen precursor catalyzed by dirhodium (II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate] complex 33e [144,145], [Rh 2 (S-TCPTTL) 4 ] which has provided, after desilylation, N-pNs-protected (S)--aminocyclohexanone 215 as a sole product in up to 72% ee (Fig. 32).…”

On the Structure of Chiral Dirhodium(II) Carboxylate Catalysts: Stereoselectivity Relevance and Insights

“…In 1993, Hashimoto, Ikegami and co-workers first reported their famous complex, Rh 2 (S-PTTL) 4 [76,77], as a catalyst that manifested (along with its variants) high enantioselectivity levels in wide range of organic transformations [2,54,[78][79][80][81][82][83][84]. For example, in enantioselective [2,3]-sigmatropic rearrangement of the cyclic propargylic oxonium ylide shown in Scheme 5a, Rh 2 (S-PTTL) 4 provided the best enantioselectivity of 79% ee of the corresponding allenic bearing benzofuran-3-one product (Scheme 5a) [85].…”

Divergent Outcomes of Carbene Transfer Reactions from Dirhodium‐ and Copper‐Based Catalysts Separately or in Combination

“…9 Consequently, we were surprised when treatment of methyl siloxyvinyldiazoacetate ( 3-Me ) with 4-nitrocinnamaldehyde at room temperature, catalyzed by dirhodium carboxylates, gave epoxide 4a with trans -divinyl substutuents in excellent yield (Scheme 3). Use of chiral catalysts that included Hashimoto’s Rh 2 ( S -PTPA) 4 10 and Davies’ Rh 2 ( S -DOSP) 4 11 did not give evidence of enantiocontrol in this transformation, and dirhodium carboxamidates exhibited very low reactivity towards dinitrogen extrusion of 3 . Surprisingly, use of Cu(CH 3 CN) 4 PF 6 , which is even more reactive towards dinitrogen extrusion from diazo compounds than is rhodium acetate, 12 gave the Mukaiyama-aldol addition product 5 in high yield when the reaction performed at 0°C without effecting diazo decomposition (Scheme 3).…”