Homoallylic bromides

The opening of cyclopropylcarbinols to homoallylic bromides constituted the first use of cyclopropyl compounds for the stereocontrolled synthesis of natural products. The cyclopropyl conjunctive reagents enhance the richness of this notion. The stereocontrolled opening of vinylcyclopropanes by a homopentadienyl proton shift provides an approach to trisubstituted olefins and thereby a new strategy. The fungal prohormone methyl trisporate B (224) as summarized in Scheme 15 illustrates this conceptual development97). 

Double alkylation of ( + )-(3/ )-ll [ ]d6 25.9 (c = 0.61, CHC13) ca. 93% ee with the dibromo compound 14, i.e., first an intermolecular alkylation by an allylic bromide, followed by an intramolecular alkylation with a homoallylic bromide, yielded (-)-15 in 54% yield and with very high diastereoselectivity60. The reaction is carried out in one pot with addition of the base, in this case potassium hexamethyldisilazanide (KHMDS), in two portions. 

In a modification of Julia s procedure, Johnson and co-workers (89) have shown that the treatment of cyclopropyl bromide (301, 0H=Br) with anhydrous zinc bromide in ether gave smoothly the trans-homoallylic bromide 302. Only... 

Homoallylic bromides, 256 Hydrocyanation, 221-242 Hydrogen bonding, 113 Hydrogen-deuterium exchange, 279-284... 

Add dropwise the remainder of the homoallyl bromide so as to maintain a moderate rate of reaction, and stir the resultant mixture at room temperature for 1-2 h.b... 

Isopropyl anisole (171) was converted to bromide (172) by metalation, formylation and bromination. Alkylation with cyclopropyl ketoester produced (173) whose transformation to alcohol (174) was achieved by saponification, decarboxylation and reduction.. Its conversion to homoallylic bromide (175) was accomplished by the method of Julia et al. [56]. Alkylation of ethyl acetoacetate with bromide (175) furnished p-ketoester (176). It was subjected to cyclization with stannic chloride in dichloromethane. The resulting tricyclic alcohol provided the olefinic ester (177) by treatment with mesylchloride and triethylamine. Epoxidation followed by elimination led to the previously reported intermediate (146) whose conversion to triptolide (149) has already been described. 

Fig (20) Bromide (172), prepared from alcohol (171) on alkylation yields (173) which is converted to (174) without any difficulty. Conversion of (174) to homoallylic bromide (175) is accomplished by the method of Julia. On alkylation followed by cyclization generated the tricyclic alcohol which undergoes dehydration to yield unsaturated ester (177) which is converted to unsaturated lactone (146) by epoxidation and elimination. 

Similarly, Takahashi and coworkers reported that treatment of alkynes with zirconocene-ethylene complex (9) and homoallylic bromides gave allylcyclo-propane derivatives [21]. Therefore, the possibility of y-elimination of the halogen atom in zirconacyclopentene intermediates appeared to be more general as expected. The plausible mechanism is shown in Scheme 13. Carbozirconation... 

The stereochemistry of the alkenyl moiety was very selective (equivalent to a syn addition). Interestingly, 2-bromo-4-pentene produced the czs-disubsti-tuted cyclopropane derivative, whereas l-bromo-2-ethyl-3-butene gave predominantly the trans isomer (Scheme 14). -Substituted homoallylic bromides did not give the corresponding cyclopropanes. 

This rearrangement also occurs in the Julia synthesis of homoallyl bromides starting with easily available cyclopropylmethyl alcohols (equation 18) These bromides are versatile electrophiles and have been involved as building blocks in many natural product preparations ". ... 

Diethyl P-keto-co-alkenylphosphonates, prepared by y-alkylation of the corresponding diethyl jj-ketophosphonates with allyl or homoallyl bromide, undergo ozonolysis at low temperature in CH2CI2 to give acyclic dicarbonyl phosphonates. Cyclization is accomplished with the aid of TsOH and EtjN as catalysts. Similarly, the diethyl 3-hydroxy-4-formylbutylphosphonate is prepared by allylation of diethyl 2-formylethylphosphonate using allyl bromide and zinc in a protic medium followed by ozonolysis and reductive workup. ... 

R = Me). In an alternative synthesis of dendrolasin, Parker and Johnson used the highly stereoselective rearrangement of the cyclopropylcarbinol (23) as the means of attaining the irons double bond in the homoallylic bromide (24). Conversion of the bromo-group to an aldehydo-group, followed by a Wittig reaction with isopropylidenetriphenylphosphorane completed the stereoselective synthesis of dendrolasin (22, R = Me). 

In the first step, the dianion generated from 17 was alkylated with homoallyl bromide to give the corresponding j8-ketophosphonate which, under typical di-... 

Toward this end, aldehyde 330 was coupled with a functionalized homoallyl anion, obtained after treatment of racemic homoallyl bromide 331 with ieri-butyllithium, to furnish diene 332. Protection of the hydroxyl group as an acetate was then followed by ring closing metathesis, employing... 

Homoallyl bromide 314, prepared from readily available non-racemic ester 313, was converted to the Grignard reagent, which reacted with non-racemic epoxide, derived from D-maUc acid, to afford the alcohol 305. Ozonolysis of the alkene gave a ketone, which was converted into enol tri-flate 316. Ni-catalyzed cross coupling with trimethylsilylmethyl magnesium chloride afforded the allyl silane, which was converted into the allyl stan-nane 317. The asymmetric allylation of 313 with 317 provided 304 with a ration of 8.5 1. Methyl etherification and oxidative cleavage of exo-methylene... 

CHPhCHPh)(PMe3). Reaction of the zirconacyclopentene Cp2ZtCH2CH2C3lCR with a homoallylic bromide yields an allylcyclopropane derivative with high isomeric purity. ... 

The Julia method for synthesis of homoallylic bromides and iodides by acid-promoted rearrangement of cyclopropylcarbinols (73) (Scheme 36) required isolation of (73), but in a new variant the Grignard adduct (74) is treated directly with mineral acid the halide formed corresponds to the halide originally present in the Grignard reagent. 

The reaction of zirconacyclopentenes with homoallyl bromides afforded al-lylcyclopropane derivatives with diastereoselectivity through intramolecular alkylation (Eq. 31) [31]. A a-substituted homoallylic bromide produced predominantly the cfs-isomer for the disubstituted cyclopropane moiety, while a j0-substituted one gave the trans-isomer as a main product. 

---