Catalytic Asymmetric Intermolecular Cyclopropanation of a Ketone Carbene Precursor by a Ruthenium(II)‐Pheox Complex

Abstract

The diazo derivative of acetonyl acetate is a useful basic skeleton for the synthesis of cyclopropyl ketones. The intermolecular cyclopropanations of diazo acetoxy acetone with olefins are accomplished by using a novel p-nitro-Ru(II)diphenyl-Pheox catalyst to give the corresponding optically active cyclopropane derivatives in good yields (up to 95%) with excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to 98% ee).

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions

“…The calculations show that the most stable starting structure is the Ru-Pheox complex with four acetonitriles coordinated in an octahedral manner, consistently with the published X-ray diffraction (XRD) structure. 4 We have confirmed by 1 H NMR that four acetonitrile ligands remain coordinated in CD 2 Cl 2 solution (see the SI ), even in the presence of styrene ( 4a ). It is important to note here that due to the lack of symmetry of the catalyst, the complex has four different positions where different species can bind (see Figure 2 ).…”

“… 25 This explains why the cyclopropanation of styrene substrates with NHPI-DA did not require syringe-pump slow addition or excess, unlike with conventional diazocompounds. 4 The concentration threshold for the olefin to operate under first-order (1-hexene; 4d ) and zero-order kinetics (styrene 4b ) correlates with the higher nucleophilicity of the latter ( N {1-hexene} = −2.77; N {styrene} = +0.78). 26 Thus, the previously empirical relationship between alkene nucleophilicity and cyclopropane yield is demonstrated to stem from a kinetic branching ratio of competing cyclopropanation and dimerization processes from a common intermediate (likely the metal carbene Int2 ).…”

“… 7 , 15 − 17 The ester substituents in diazocompounds have been modified to enhance diastereo- and/or enantioselectivity by adjusting their size and/or enabling chelate intermediates with the catalyst. 4 , 18 The unique performance of NHPI-DA ( 1a ) in combination with Ru-Pheox ( 2 ) observed by Mendoza and co-workers, 5 and the limited experimental data on the mechanism of cyclopropanation and dimerization reactions (particularly on ruthenium metallacyclic catalysts), prompted us to conduct a joint experimental–computational study to discern the key mechanistic features that enable the unusual and interesting applications that have been recently discovered. 5 , 19 …”

Ruthenium Carbene-Mediated Construction of Strained Allenes via the Enyne Cross-Metathesis/Cyclopropanation of 1,6-Enynes

“…In particular, the trapping of ruthenium carbene with an alkene chain via a [2 + 2] cycloaddition/metal reductive elimination process generally produces cyclopropane-containing products . Several interesting examples were presented by Iwasa et al, who used the ruthenium phenyloxazoline complex as a catalyst in the coupling reaction of diazoester and alkene/allene to produce cyclopropyl ester/ketone . In the typical examples reported by Dixneuf, an intramolecular alkene side chain of enynes was utilized as a capture partner to successfully realize a cyclopropanation process to access alkenyl bicyclo[3.1.0]­hexane (Scheme A 2 ) .…”

Catalytic Asymmetric Carbene Transfer Reactions of Diazo Oxime Ethers with Olefins and Their Synthetic Applications

“…The structure and absolute configuration of cyclopropyl oximes (major trans product) were determined in an efficient manner by comparison of cyclopropyl oximes with the synthetic transformation of a cyclopropyl ketone into a cyclopropyl oxime product. As shown in Scheme , diphenyl cyclopropane ketone 5 having only the trans isomer was successfully transformed into a mixture of anti and syn isomers 3b′ bearing an oxime functional group. Besides, trans and cis cyclopropyl oxime products 3b were produced by the reaction of α-diazo oxime ether 2a with styrene 1b , as mentioned before.…”