A General Synthesis of Methylenecyclopentanes by a Stereoselective [3 + 2] Approach

Abstract

The [3 + 2] cyclopentanation involving 3-(phenylsulfonyl)-2-(bromomethyl)-1-propene (1) and representative (E) α,β-unsaturated acyclic esters and ketones has been studied. High yields and complete stereoselectivity were observed in all reactions leading to tri- or tetrasubstituted methylenecyclopentanes. The anti-diastereoselectivity in the first, Michael addition step is rationalized by a chelation-controlled transition state in which MO interactions of the two π systems are involved. The Michael reactions of methallyl sulfone 8 with (E) enoates in the absence and presence of HMPA confirms the influence of chelation on the diastereomeric ratio of adducts. Cyclopentanations involving 1 with cyclohexenone, 2(5H)-furanone, and 5,6-dihydro-2-pyranone, respectively, were also studied with emphasis on the factors influencing the stereochemical outcome of the annulation process.

The role of an aromatic group in remote chiral induction during conjugate addition of α-sulfonylallylic carbanions to ethyl crotonate

“…By analogy with previous work on conjugate addition of α-sulfonylallylic carbanions to open-chain α,β-unsaturated esters, which has been shown to proceed anti -diastereoselectively [ 2 , 13 ] and with the N (1) R *,3 S *,4 R * relative configuration predominating [ 1 ], we assign our major and minor products structures 3 and 4 respectively (showing in Scheme 1 only one enantiomer for each racemate).…”

“…A series of α-sulfonylallylic donor precursors 1 , bearing a remote stereogenic center, were prepared by condensing a chiral aryl- or heteroarylalkylamine 6 with the bromo-substituted allyl sulfone 5 [ 2 ] ( Scheme 2 and Table 1 ).…”

“…Of the four possible diastereoisomeric conjugate addition products resulting from the formation of two new stereogenic centers (methine carbon atoms 3 and 4 of the ethyl hexenoates, see Scheme 1 ) only two could be detected in all cases except the 9-anthryl derivative ( 3h ), which indicated a single adduct. Apart from having proceeded regioselectively (α- rather than γ- to the sulfone functionality), the addition was thus diastereoselective as well [ 2 , 13 ]. Both the ratio between the diastereoisomeric adducts 3 and 4 as well as the extent of reaction (% conversion) were determined by comparing the integration values for the distinct olefinic proton signals of the non-separable addition products and of any unreacted starting amino-substituted sulfone 1 [ 14 ].…”

“…We had proposed that π–Li + interaction may be responsible for this phenomenon. We had shown earlier [ 2 ] that conjugate addition of lithiated allyl sulfone 5 to unsaturated esters of type 2 takes place α-regioselectively and almost exclusively in an anti fashion (where the syn and anti designations are based on the extended form including both anion stabilizing groups [ 3 ]). Hence, it was not surprising that both diastereomeric products, 3 and 4 , of the addition of 1 to 2 , possessed the anti configuration.…”

Asymmetric Induction by a Remote Chiral Substituent – Computationally Determined Stereodifferentiation in Michael Additions of α‐Lithiated Allyl Sulfones

“…Asymmetric induction caused by a chiral molecular unit is a function of the proximity of the chiral fragment to the reaction center, leading to differentiation of diastereotopic stereofaces by an approaching reagent. In this context, the high stereoselectivity that has been observed for reactions of allylic α‐sulfonyl carbanions containing a neighboring chiral auxiliary with different electrophiles1a–1e has been convincingly explained1d by modeling the electrophile approach to anion substrates of optimized geometry.…”