Synthesis of nitrocyclopentanes via a 3+2 strategy

Abstract

Reactions of l-(phenylsulfonyl)-2-methylene-3-bromopropane (1) with various nitroolefins have been investigated with the purpose of devising a tandem [3 + 21-annulation leading to nitro-substituted derivatives of methylenecyclopentanes. The conjugate addition step occurred readily affording 4a-e (syn) and 5a-e (anti) adducts. The anti-adducts cyclized further in the presence of HMPA to give stereoisomeric methylenecyclopentane derivatives 6a-f and 7a-f. At higher reaction temperature, partial ring closure of 4a-d-syn isomers to give cis-2,3-disubstituted cyclopentanes 8a-d could also be achieved. Base-induced equilibration provided in a one-vessel operation, starting from 1 and 1-nitrobutene (3b), the methylenecyclopentane 6b with three stereogenic centers. The difference in the stereochemical outcome of the Michael addition step with nitroolefins, as compared with reactions in which a,fl-unsaturated esters served as acceptors for 1, may be attributed to the better chelating ability of the lithium counterion in the latter reactions, based upon the results obtained in conjugate additions of methallyl sulfone 9 with 1-nitropropene and crotonic ester. The presence of HPMA strongly influenced the stereochemical outcome of reactions of 9 with ethyl crotonate but not with 1-nitropropene as the Michael acceptor. Reactions of 1 with 1-nitro-2-arylethenes afforded trans-trans-substituted methylenecyclopentanes as the major products. The reaction of 1 with 1-nitrocyclohexene afforded the cis-hydrindane derivative 21. The described reactions provide the first example of intramolecular trapping of nitronates resulting from Michael additions by alkyl/allyl halides.

Stereoselective Michael Additions of Phosphorylated Allyl Carbanions − Synthesis of Functionalized Cyclopentylphosphonates and Phosphane Oxides

“…The change in regioselectivity may be due to the fact that the nitro group is not a good Li ion chelator. [18] Conclusion Allylphosphonate 3b and allylphosphane oxide 3d, incorporating allyl chloride moieties, and thus representing the first P-containing methylenemethane equivalents, have been prepared and their MIRC reactions with unsaturated esters and ketone 5aϪd examined. The Michael addition proceeded with high anti stereoselectivity and α-regioselectivity to form P-substituted methylenecyclopentanes.…”

Regioselectivity of the Reactions of Heteroatom-Stabilized Allyl Anions with Electrophiles

“…The influence of chelation evidently favors the formation of anti-diastereomer, since the chelation ability decreases for nitropropene. Whereas in case of α,β-unsaturated esters open chain products 772 could not be detected, only the anti -nitro derivative 773 cyclizes easily forming 775 (Scheme ). ,

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A Highly Stereoselective One-Pot Tandem Consecutive 1,4-Addition−Intramolecular 1,3-Dipolar Cycloaddition Strategy for the Construction of Functionalized Five- and Six-Membered Carbocycles,1

“…Cyclopentanoids are precursors to prostaglandins and a plethora of other natural products , However, since the [3 + 2] annulation strategy, by far, is largely dependent on trimethylenemethane (TMM) precursors and often requires transition metal catalysis, ,6a,b alternative avenues involving intramolecular thermal additions of oximes,6e nitrile oxides, 6f, and silyl nitronates 6f providing cyclopentanes fused to an isoxazolidine or isoxazoline moiety are of considerable interest. The scope and effectiveness of the latter approaches are so striking in that they serve the twin purpose of generating a carbocycle and a heterocycle fused to each other in an essentially single operation.…”