First Highly Regio- and Diastereoselective [3+2] Cycloaddition of Chiral Nonracemic Alkenyl Fischer Carbene Complexes with Diazomethane Derivatives: Preparation and Synthetic Applications of Enantiomerically Pure Δ2-Pyrazolines

Abstract

The [32] cycloaddition of alkenyl Fischer carbene complexes 1 and 6 with diazomethane derivatives to give D 2 -pyrazoline carbenes 2, 4, and 7 is described. The conversion of (À)-8-phenylmenthol-derived carbenes 6 into pyrazoline esters 9 through a one-pot cycloaddition ± protection ± oxidation is presented as an expeditious route to enantiomerically pure 3-alkoxycarbonyl-D 2 -pyrazolines in good yields and in a highly regio-and diastereoselective manner. Pyrazolidines 13 were synthesized in excellent overall yields from 9 through pyrazolines 11 and 12, the diastereoselective reduction of CN bond being the key step. Azaprolines 16 and 17 were prepared in very good yields from epimeric trans-13 or cis-13 by oxidative deprotection of the silylated hydroxy group. In an alternative reaction, the pyrazolidine ring of 13 was reduced to obtain protected openchain 2,4-diamino alcohols 19 with three chiral centers.

Synthesis of nitrogen‐containing compounds using chromium Fischer carbene complexes

“…The observed diastereofacial selectivity on the alkene moiety of the complex 5a was opposite to those of other reported reactions 22. Therefore, we assumed that the [4+2] cycloaddition reaction of the 1‐chroma‐1,3‐butadiene system with the CN double bond23 occurs via s ‐ cis conformation, where the imine approaches from the less hindered Si face of the carbene carbon (Scheme ).…”

New heterocyclization reactions with Fischer carbene complexes

“…For instance, they allow the synthesis of 4,5-dihydro-1H-pyrazole esters 7 in the one-pot procedure shown in Scheme 3. 4 Thus, the [3+2] cyclization reaction of alkenyl carbenes 6 with diazomethane derivatives in THF at room temperature, followed by BOC protection and subsequent oxidation of the carbene moiety leads to the corresponding ∆ 2 -pyrazoline derivatives as single diastereomers in yields ranging between 55 and 79%. It is necessary to point out that Fischer carbenes are much more reactive in this transformation than the corresponding chiral esters.…”

“…16 When monosubstituted fulvenes were used, homofulvenes 64 were obtained as an E/Z mixture, except for the compound derived from t-butylfulvene, isolated as a single E-isomer. The homofulvene derived from 6,6-dimethylfulvene undergoes a second cyclopropanation with two different reagents: i) reaction with ethyl diazoacetate/Rh 2 (OAc) 4 produced the tricyclic compound 65 as a 4:1 mixture of epimers, which after final ozonolysis and acid hydrolysis led to the elaborated cyclopentanone 66; ii) reaction with the chromium alkenyl carbene indicated formed the cyclopentannulation adduct 67 as the major diastereoisomer (60% de) after heating the mixture in THF at 100ºC (in sealed tube) and subsequent acid hydrolysis. Further ozonolysis and hydrolysis of the major diastereoisomer led to the functionalized diquinane 68 in 95% yield.…”

Intramolecular CH Oxidative N‐Allylation of C‐Homoallylhydrazones to 5‐Vinyl‐2‐pyrazolines Catalyzed by the [Pd(OAc)2]/BIMINAP System

“…Nevertheless, alternative [2+3] processes have been devised for the synthesis of 2‐pyrazolines with specific substitution patterns from hydrazine equivalents and other three carbon electrophiles, such as homopropargylic alcohols,8 ynones (giving hydrated pyrazoles),9 1,3‐dihaloalkanes (through concomitant oxidation of the primary pyrazolidine product),10 or 2‐acylaziridines 11. Although 5‐carbonyl, 5‐cyano, and 5‐aryl‐2‐pyrazolines have been extensively studied,1 only a few vinyl‐substituted pyrazolines have been prepared, for example by [3+2] cycloaddition of diazoalkanes with Fischer carbene analogues of acrylic CC double bonds 12…”