Synthesis of Highly Substituted γ‐Butyrolactones by a Gold‐Catalyzed Cascade Reaction of Benzyl Esters

Easily accessible benzylic esters of 3‐butynoic acids in a gold‐catalyzed cyclization/rearrangement cascade reaction provided 3‐propargyl γ‐butyrolactones with the alkene and the carbonyl group not being conjugated. Crossover experiments showed that the formation of the new C?C bond is an intermolecular process. Initially propargylic–benzylic esters were used, but alkyl‐substituted benzylic esters worked equally well. In the case of the propargylic–benzylic products, a simple treatment of the products with aluminum oxide initiated a twofold tautomerization to the allenyl‐substituted γ‐butyrolactones with conjugation of the carbonyl group, the olefin, and the allene. The synthetic sequence can be conducted stepwise or as a one‐pot cascade reaction with similar yields. Even in the presence of the gold catalyst the new allene remains intact.     

Highly Enantioselective Iridium‐Catalyzed Hydrogenation of α,β‐Unsaturated Esters

α,β‐Unsaturated esters have been employed as substrates in iridium‐catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99 % ee) were obtained for a broad range of substrates with both aromatic‐ and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals.     

Stereoselective Access to γ‐Nitro Carboxylates,Precursors for Highly Functionalized γ‐Lactams

A straightforward synthesis of the enantiomerically pure nitro derivatives 31 and epi‐ 32 , which are particularly useful intermediates for the synthesis of highly functionalized γ‐lactams, is presented. (+)‐(R)‐3‐Hydroxy‐3‐phenylpropanoic acid ( 20 ) and its ethyl ester 25 were prepared from (+)‐L ‐mandelic acid ( 21 ). Condensation of 20 with pivalaldehyde furnished the novel enantiomerically pure 1,3‐dioxan‐4‐one 17 , the absolute configuration of which was established by X‐ray crystal‐structure analysis. Treating the lithium enolate of 17 with the nitro alkene 18 led, in a Michael‐type addition, to a 1 : 1 mixture of two diastereoisomeric products. The stereocontrol of the addition was limited to the novel stereogenic center next to the lactone function. When the lithium enolate of 25 was treated with 18 , the same selectivity was observed but with a lower chemical yield. Very facile separation of the isomers was achieved later in the synthetic sequence, when one isomer cyclized selectively to the nitro lactone 31 , while the other one was isolated as hydroxy ester epi‐ 32 . The relative configuration of racemic epi‐ 32 could be established by X‐ray crystal‐structure analysis.     

Base‐Catalyzed Highly Stereoselective Conversion of γ‐Hydroxy‐α,β‐acetylenic Esters to γ‐Acetoxy Dienoates

A convenient route with high stereo control to γ‐acetoxy dienoates is provided by the reaction of methyl propiolate with aldehydes in the presence of ZnEt₂ and N‐methylimidazole at room temperature, followed by the catalytic conversion of the resulting γ‐hydroxy‐α,β‐acetylenic esters with p‐N,N‐dimethylaminopyridine (DMAP) in acetic anhydride (see scheme).

     

Highly Selective Allylborations of Aldehydes Using α,α‐Disubstituted Allylic Pinacol Boronic Esters

α,α‐Disubstituted allylic pinacol boronic esters undergo highly selective allylborations of aldehydes to give tetrasubstituted homoallylic alcohols with exceptional levels of anti‐Z‐selectivity (>20:1). The scope of the reaction includes both acyclic and cyclic allylic boronic esters which lead to acyclic and exocyclic tetrasubstituted homoallylic alcohols. The use of β‐borylated allylic boronic esters gave fully substituted alkenes bearing a boronic ester which underwent further cross‐coupling enabling a highly modular and stereoselective approach to the synthesis of diaryl tetrasubstituted alkenes. Computational analysis revealed the origin of the remarkable selectivity observed.     

Controlled Heterocyclization/Cross‐Coupling Domino Reaction of β,γ‐Allendiols and α‐Allenic Esters: Method and Mechanistic Insight for the Preparation of Functionalized Buta‐1,3‐dienyl Dihydropyrans

Starting from β,γ‐allendiols and α‐allenic acetates, a chemo‐ and regiocontrolled palladium‐catalyzed methodology has provided access to enantiopure 3,6‐dihydropyrans that bear a buta‐1,3‐dienyl moiety. Thus, it has been demonstrated for the first time that the preparation of six‐membered heterocycles through cross‐coupling reactions of two different allenes can be accomplished. These heterocyclization/cross‐coupling reactions have been developed experimentally and their mechanisms have additionally been investigated by a computational study.     

One‐Pot Synthesis of Functionalized 3‐Aryl‐1‐phenyl‐1H‐pyrazoles from Hydrazonoyl Chlorides and Acetylenic Esters in the Presence of Ph3P

The zwitterionic 1 : 1 intermediates generated by addition of Ph₃P to acetylenic esters is trapped by 1‐[(aryl)chloromethylene]‐2‐phenylhydrazines (=N‐phenylarenecarbohydrazonoyl chlorides) to yield functionalized 3‐aryl‐1‐phenyl‐1H‐pyrazoles in good yields.