Cyclopropyl boronic ester

Scheme8.25 Synthesis of asymmetric (cyclopropyl)boronic esters.

Pietruszka has reported the synthesis of styryl and cyclopropyl boronic esters with an acrylate functionality by applying a cross-metathesis reacTion (%]. Thus, the reaction of cyclopropyl boronate 122 with methyl acrylate gave the E-enoate 123 in 52% yield (Scheme 3.63). 

Synthesis and Reactions of Functionalized Cyclopropyl Boronic Esters... 

Pietruszka has reported the synthesis of stable enantiomerically pure functionalized cyclopropyl boronic esters via highly diastereoselective cyclopropanation of the respective alkenyl boronic esters with diazomethane catalyzed by Pd(OAc)2(119]. The enantiomerically pure alkenyl boronic esters were prepared by direct hydroboration of the respective alkynes with the chiral 1,3,2-dioxaboro-lane (144). The ter-butyldimethylsilyl protecting group in the boronic ester could be selectively deprotected and the resulting hydroxymethyl alkenyl boronate was also cyclopropanated to give hydroxymethylcyclopropyl boronic esters with good diastereoselectivity (Scheme 3.78). 

Scheme 3.79 Synthesis of functionalized Ws-(cyclopropyl) boronic esters.

Without question, the most important developments in this field over the past 10 years have been in the area of enantioselective hydroborations. New chiral catalyst systems are typically tested in hydroborations of vinyl arenes, as reactions using HBcat and a cationic rhodium catalyst are well known to give selective formation of the unusual branched isomer. In related studies, enantiopure 2,2-disubstituted cyclopropyl boronates were easily prepared via the catalytic asymmetric hydroboration of 3,3-disubstituted cyclopropenes using a number of chiral neutral rhodium complexes (equation 13). Directing groups, such as esters and alkoxymethyl substituents, were necessary for achieving... 

SAR studies were performed on compoimds containing the 9H-isothia-zolo[5,4-fc]quinoline-3,4-dione (ITQ) nucleus and it was found that some of them are potent antibacterial agents (see Scheme 101) [114,115]. They were prepared from compound 353, which was treated with cyclopropyl isothiocyanate in DMF and then with Mel. Compound 354 (94%) was obtained and treated with in NaH in DMF to give the isothiazolo[ 5,4-fo] quinoline compound 355 (93%). Its treatment with anhydrous NaSH gave the corresponding mercaptan (84%), which was directly cychsed without purification to 356 (85%) in the presence of hydroxylamine-O-sulfonic acid. Microwave-assisted Suzuki-Miyaura cross-coupling of the ITQ nucleus 356 with the desired aryl-boronic esters or acids afforded derivatives 357, typically, in 30-50% yield after HPLC purification (Scheme 87). 

Cyclopropanes and their derivatives are versatile building blocks in organic synthesis. They are also present in many natural products and frequently included as substituents in the structure of new biologically active substances. While cydopropylbo-ranes have long been described [34], it is only since an efficient access to the boronic esters was reported that they really attracted chemist s interest. In 1989, the first additions of carbenes, generated from diazo compounds and palladium acetate, to pina-col alkenylboronic esters were reported to give racemic mixtures of cyclopropyl-boronates (Scheme 9.15) [35]. 

High enantioselectivities are obtained using N,N,N, N -tetramethyltartaric acid diamide-derived boronate ester 32 in combination with bis(iodomethyl)zinc for asymmetric cyclopropanation of allylic alcohols. Various chiral, non-racemic cyclopropyl-methanols can be obtained in enantiomeric excesses of 91-94%. This methodology has been extended with success to the cyclopropanation of unconjugated and conjugated polyenes and homoallylic alcohols (Equation 47) [45]. 

Scheme 3.65 Cross-coupling of boronic esters with cyclopropyl iodides.

This q clopropyl boronic ester was converted into fois-cyclopropanes through a series of transformations shown in Scheme 3.79 [120], The iodo fois-cyclopropyl boronic acid ester 145, however gave a complex product mixture on attempted Suzuki coupling with phenylboronic acid. On the other hand, the less bulky hydroxy protected fois-cyclopropyldioxaborinane 146 obtained by transesterification underwent smooth cross-coupling with iodobenzene giving the phenyl substituted fois-cyclopropane product 147 in 79% yield (Scheme 3.79). 

This section covers the formation of cyclopropanes via cyclization of reactive allylic intermediates (cations, anions, radicals). Included are those transformations of allylic functional derivatives (e.g. allylic halides, alcohols, aldehydes, ketones, acids, esters, boronates, Grignard reagents) to cyclopropyl derivatives that do not actually proceed via allylic reactive intermediates, but which are not covered by other sections of this volume. Additionally, this section will cover methods for the formation of cyclopropanes by pericyclic reactions. 

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