Bromo homoallylic alcohols

The reaction of 2,3-dibromopropene with racemic as well as enantiopure 4-oxoazeti-dine-2-carbaldehydes (1) in aqueous media was promoted by tin in the presence of catalytic amounts of different Lewis or protic acids (additives) to afford the corresponding bromo homoallylic alcohols (2) in high diastereoselectivities. In terms of achieving good yields and stereoselectivities, BiCU was considered the most promising candidate for further reactions (Equation 1) [25a]. 

With functionalized allylic bromides, the same procedure allowed preparation of bromo-homoallylic alcohols and 1,3-ketoacetates (Mandai et al., 1984) or a-methylene-y-butyrolactones (Nokami et al., 1986). 

Mandai, T. Nokami, J. Yano, T. Yoshinaga, Y. Otera, J. (1984) Facile one-pot synthesis of bromo homoallyl alcohols and 1,3-keto acetates with allyltin intermediates, J. Org. Chem. 49,172-4. 

An unusual Pd-catalyzed cross-coupling reaction of a diindium reagent obtained from 3-bromo-l-iodopropene 6/1-239 was recently described by Hirashita and coworkers [118] to afford homoallylic alcohols 6/1-240 (Scheme 6/1.62). 

Allylindium reagents bearing substituents at the 7-position react with carbonyl compounds in organic and aqueous media regioselectively at the 7-position, via a six-membered transition state, to afford the corresponding branched homoallylic alcohols, if no sterically bulky carbonyl or allyl substituent is involved.102 For example, the indium-mediated reaction of aldehydes with 3-bromo-l-cyano-l-propene proceeds readily in water to give cr-cyano-f3-ethylenic secondary alcohols (Scheme 4).103... 

Indium-mediated reaction of 4-bromo-l,l,l-trifluoro-2-butene with aldehydes in water proceeds stereoselectively to afford the /Ttrifluoromethylated homoallylic alcohols. Aldehydes with no chelation ability shows //////-selectivity, whereas high. //-selectivity has been attained with 2-pyridinecarboxaldehyde and glyoxylic acid (Scheme 23).134-136... 

Indium-mediated Barbier-type reaction of glyoxal monoacetal with bromomethyl acrylonitrile or bromomethyl-acrylate gives a masked a-hydroxy aldehyde (Equation (48)).91 The reaction of 3-bromo-2-chloro-l-propene, an aldehyde, and indium in water gives the corresponding homoallyl alcohol, which upon ozonolysis in methanol furnishes a / -hydroxy ester. The overall reaction is equivalent to the Reformatsky reaction, which cannot be realized by a direct indium-mediated reaction of an ct-halo ester with an aldehyde in water (Scheme 59).235... 

With inspiration from extensive studies on the synthesis and biological activities of 2 -deoxy-2,2 -difluoronucleosides, 3 -dcoxy-3, 3 -di(luoro-i>-ara/mo-furanosyl nucleosides were stereoselectively synthesized, featuring a novel and efficient strategy to prepare 3-dcoxy-3,3-di(luoro-D-ara >m<9-furanosc 7 via chiral gem-A (1 uorohomoallyl alcohol 2 [4], In the presence of indium powder, the reaction of (7 )-glyceraldehyde acetonide 1 with 3-bromo-3,3-difluoropropene gave difluorohomoallyl alcohol 2 in 90% yield as a mixture of two diastereoisomers in a ratio of 7.7 1. Without separation, homoallyl alcohol 2 was subjected to benzylation. When 1.6 equivalents of NaH were used, benzylated compound... 

A -Boc amines are made from the metallated /-hutyl Af-tosyloxycarbamate. Allylic displacements. Applications of this process include vinyl- and allyltin compounds. Homoallylic alcohols asymmetrically substituted at the allylic position are obtained from 4-bromo-2-alkenoyl derivatives of camphor sultam in two... 

The bromo compound 269 was prepared from the commercially available homoallyl alcohol (263) as follows Tritylation of 263 gave the ether (264), which was converted by treatment with perbenzoic acid to epoxide 265. The latter was converted to methoxyl alcohol 266 by opening the... 

The 3-borolene ate complexes (56) are derived from 3-borolene (55) and an alkyllithium compound. They react with dimethyl sulfate or l-bromo-3-methyl-2-butene in a regio- and diastereo-selective manner to furnish, after oxidative work-up, the corresponding substituted homoallylic alcohols (57) and (58) (Scheme 10) <87JOC5484>. 

When carried out with ( )-rich l-bromo-2-butene in THF/H2O solution, the SnCla Barbier-type allylation of aldehydes provided homoallylic alcohols, mainly with the anti configuration. By contrast, syn allylation occurred with tin(ll) iodide (Scheme 4.1). The syn-selectivity, suggesting an acyclic antiperi-planar transition state, was even improved by the addition of tetrabutyl-ammonium bromide in the aqueous medium. This enhancement of selectivity could be explained by the formation of a pentacoordinated tin species, preventing the tin atom from coordinating the oxygen atom of the aldehyde (Masuyama el a/., 1996). 

Indium Lewis acids have garnered attention due to their mild reactivity and air and water stability. Both Li et al. and Chan and Loh have shown that In(III) complexes are suitable Lewis acids for Prins cyclizations [81, 82]. These reports prompted Loh and coworkers to embark on a synthesis of (+)-SCH 351488 that utilized this strategy (Scheme 40) [83]. Condensation of homoallylic alcohol 147 and aldehyde 148 in the presence of indium ttibromide and TMSBr gave 4-bromo THP 149 in 65 % overall yield as an inconsequential mixture of diastereomers (2,A-cisP,4 trans = 75 25). Complete retention of the homoallylic alcohol stereochemistry is responsible for the key 2,6-cis relationship in the product. Initial attempts to apply these same conditions to the B ring resulted in acetonide deprotection and no THP formation. Subsequent optimization revealed that indium triflate and TMSCl were competent additives to effect cyclization. Careful temperature control was required to suppress an undesired Prins side reaction. The combination of homoallylic alcohol 150 and aldehyde 151 in the presence of the appropriate Lewis acids at 78 °C, followed by warming to 0 °C for 4 h, led to the desired monomer precursor 152 in 42 % yield. 

A series of homoallylic tertiary alcohols [3] with structure 1-aryl-l-(A -cyclohexenyl)ethanol are synthesized by treating p-haloacetophenone with B-2-cyclohexen-l-yl-9-BBN (Eq. 6.9). Apparently, it is not feasible to convert 1-chloro- or l-bromo-2-cyclohexene into the corresponding Grignard reagent. 

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