[3,3]‐Sigmatropic Rearrangement/Allylboration/Cyclization Sequence: Enantioenriched Seven‐Membered‐Ring Carbamates and Ring Contraction to Pyrrolidines

Abstract

The combination of in situ generated a-isocyanato allylboronic esters and aldehydes afforded seven-memberedring enecarbamates with high levels of diastereo-and enantiocontrol. They were easily converted into diversely substituted 1,3-oxazepan-2-ones.A nu nprecedented rearrangement of 5-acetoxy-7-aryl or styryl derivatives led to tetrasubstituted pyrrolidines.Acomputational study provides evidence on the feasibility of the proposed mechanism of this unusual ring contraction.Nitrogen heterocycles are widespread in ap lethora of molecules of interest, either in materials science,e lectronics, optics,o rb iology.[1] Among these,s even-membered-ring carbamates are relatively under-represented despite their interesting biological activities.[2] Several approaches are available for their synthesis,a nd the most common ones are based on intramolecular cyclization of 1,4-aminoalcohols or derivatives.[3] Others are restricted to isolated examples or very particular structures.[4] Our interest in the use of boronic esters in cascade reactions [5] led us to consider their utility for the synthesis of enantioenriched 4,5-dihydro-1,3-oxazepin-2-ones.T hese versatile intermediates led, through an unprecedented ring contraction reaction, to tetrasubstituted pyrrolidines,another family of major biological significance.Access to the key carbamates 1 was first achieved from optically active 1-alkyn-3-ols. [6,7] Dehydration with phosphine and carbon tetrabromide in the presence of triethylamine, [5d] followed by direct addition of aldehydes to the crude reaction mixture,a nd then aqueous NaHCO 3 15 hours later, afforded the cyclic ene carbamates 5 in good to moderate yields (threestep process;T able 1). Thestructure of 5 was assigned on the basis of NMR data and X-ray crystallographic analysis of 5a.[8]Thef ollowing mechanism can be proposed. After dehydration of 1,t he resulting allylcyanate 2 undergoes a[ 3,3]-sigmatropic rearrangement which affords the a-isocyanato allylboronate 3 (Scheme 1).[5d, 9, 10] Ac hairlike transition state [a][a] The reactions were carried out by addition of asolution of CBr 4 (0.56 mmol, 2.8 equiv) in CH 2 Cl 2 (0.5 mL) to amixture of 1 (0.2 mmol), polymer-supported phosphine (2.5 equiv),and Et 3 N(0.4 mmol, 2equiv) in dry CH 2 Cl 2 (2 mL). The aldehyde (0.24 mmol, 1.2 equiv) was added after 6hat 0 8 8C. The mixture was maintained at RT for 15 hbefore quenching with aqueousN aHCO 3 .[ b] Yield of product isolated after silica gel chromatography.