Modulable and Highly Diastereoselective Carbometalations of Cyclopropenes

Abstract

The copper-catalyzed carbomagnesiation reaction of cyclopropenyl esters 1 leads to various substituted cyclopropanes species 3 in good yields with very high diastereoselectivities. The reaction proceeds through a syn-chelated carbomagnesiation reaction and could be extended to various cyclopropenylmethyl ester derivatives 5. The potential of this approach was illustrated by the preparation of two consecutive all-carbon quaternary stereocenters. However, the carbometalation reaction needs to be performed at temperature ranging from -35 to -20 °C to avoid subsequent fragmentation reaction into stereodefined β,γ-nonconjugated unsaturated esters 4. Alternatively, the carbocupration reaction with organocopper species could also be performed to leads to configurationally stable cyclopropyl copper species 2[Cu]. Additionally, when the Lewis acid character of the copper center is decreased (i.e., RCuCNLi), the reaction proceed with an anti-selectivity. The diastereodivergent behavior of these organometallic species is of synthetic interest, since both diastereomers syn-3 and anti-3 can be obtained, at will, from the same precursor cyclopropenyl esters 1.

Copper mediated carbometalation reactions

“…The occurrence of small amounts of free alkyllithium in the presence of RCuCNLi was able to reverse the facial selectivity back to the expected syn -selectivity which is probably due to the better availability of lithium ions for chelation (Scheme 14). 63 …”

“…The depicted vinyl sulfones 16 and 17 were obtained from the corresponding alkenyl iodide 18 via an addition–elimination sequence or from the alkyne 19 via addition-hydrolysis (Scheme 15). 63 …”

“…If the reaction is warmed up to 0 °C, a stereospecific fragmentation reaction occurs (Scheme 36). 63 …”

“…First, the ring opening of cyclopropyl-magnesium species containing an ester group as an electron withdrawing group was observed upon warming the reaction to 0 °C (Scheme 36). 63 The formation of the alkene is highly selective due to the preorganized position of the substituents in the cyclopropane scaffold (eqn (2), Scheme 35). …”

“…63 The diastereodivergent carbometalation reaction of cyclopropenyl esters (Schemes 13–15) was cleverly exploited to access both enantiomers of the corresponding aldehyde ( S )-42 and ( R )-42 starting from the same cyclopropenyl ester 41 (Scheme 37). It is noteworthy that in the case of copper-catalysed carbomagnesiation, molecular oxygen provided clean oxidation without leading to dimerized products which are typically observed with organocopper reagents.…”