1.1- dibromo-l-alkenes

The dehalogenation of organic halides by organotin hydrides takes place in most cases with a free-radical mechanism [1, 84, 85], The stereospecific reduction of 1,1-dibromo-l-alkenes with Bu3SnH discovered by Uenishi and coworkers [86-89], however, did not occur in the absence of palladium complexes and did not involve radicals. For the synthesis of (Z)-l-bromo-l-alkenes, [(PPh3)4Pd] proved to be the most effective catalyst which could also be generated in situ. The reaction in Eq. (7) proceeded at room temperature and a wide range of solvents could be used. 

The authors determined the optimal reaction conditions and illustrated the scope of the method with 32 different starting compounds including alkenyl-, alkynyl-conjugated and 2,2-disubstituted 1,1-dibromo-l-alkenes. 

A synthesis of potentially useful 1-iodo-l-bromo-l-alkenes has thus been developed that offers complete stereocontrol. These methods have also proven to be highly efficient for the preparation of 1,1-diiodo-l-alkenes and 1,1-dibromo-l-alkenes, which are very useful synthetic intermediates (Scheme 7.26) [155]. 

In 2002, Figad re and coworkers reported the mono-reduction of 2-aryl (or heteroaryl)-1,1-dibromo-l-alkenes (Scheme 23). The reaction is achieved with one equivalent of isopropylmagnesium chloride in the presence of iron(III) acetylacetonate. Pure ( )-alkenyl bromides are obtained. With two equivalents of alkyl Grignard reagent, the mono-substituted product is obtained in moderate yield. 

The second substitution of 1,1-dibromo-l-alkenes involved the Pd-catalyzed crosscoupling reactions of 6-8 obtained as shown in Scheme 37. Quite unexpectedly, the reaction of 6a with MeZnBr in the presence of several Pd-phosphine catalysts produced the expected cross-coupling products of >95% stereoisomeric purity in 76-91% yields, but careful ID NOE analyses have firmly established that the reaction was accompanied... 

SCHEME 37. /rtfas-Monosubstitution of 1,1-dibromo-l-alkenes with alkenyl-, alkynyl- and aryl-zincs in the presence of Pd(DPEphos)Cl2 as a catalyst... 

The (E)-bromides in 1,1-dibromo-l-alkenes can be stereoselectively coupled with aryl- or al-kenylboronic acids to give the corresponding (Z)-l-aryl(or alkenyl)-l-bromo-l-alkenes. Tris(2-... 

The currently available methods for the synthesis of the title compounds are confined to the preparation of homo-1,1-dihalo-1-alkenes 180 while only a few reports are available for mixed 1,1-dihalo-1-alkenes of defined stereochemistry 18u. As the hy-droboration reaction proceeds in a stereospecific manner, the hydroboration-oxi-dation-bromination-debromoboration sequence of 1-chloro-l-alkynes produces selectively (Z)-l-bromo-l -chloro-l-alkenes (Eq. 116),82>. The oxidation with anhydrous trimethylamine oxide of the alkenylborane prior to the addition of bromine is necessary to avoid the competing transfer of one of 1,2-dimethylpropyl group from boron to the adjacent carbon atom. Similar reaction sequence provides 1,1-dibromo-l-alkenes (Eq. 117)182). 

A method for the palladium - catalysed synthesis of alkynylphosphonates (206) from 1,1-dibromo-l-alkenes (207) has been developed. The best catalyst system for this transformation was Pd(OAc)2, dppf, H-phosphonate (208). The reaction appears tolerant of a range of functional groups in both (207) and (208) (Scheme 53). ... 

Symmetrical and unsymmetrical 1,3-diynes have been prepared from 1,1-dibromo-l-alkenes. Alkynylpalladium intermediates undergo homocoupling when Cul is present in the reaction medium. On the other hand, the persistent intermediates can await addition of other 1-alkynes for their ultimate transformation. 

French chemists have been able to increase the yields to 85-90% by use of a 40 60 mixture of THF—ether as solvent instead of pure THF. Note that Corey and Fuchs (4, 550) have prepared 1,1-dibromo-l-alkenes by the reaction of an aldehyde with triphenylphosphine, carbon tetrabromide, and zinc in methylene chloride. 

Distannyl-l-alkenes can be prepared from 1,1-dibromo-l-alkenes (Scheme 64). Temperature control is important for the success of... 

Ketene-S,S-acetals have been prepared by the Ni(II)-catalysed displacement of 1,1-dibromo-l-alkenes with thiolates. The same method... 

Uenishi, J. et al.. Stereoselective hydrogenolysis of 1,1-dibromo-l-alkenes and stereospecific synthesis of conjugated (Z)-alkenyl compounds, J. Org. Chem., 63, 8965, 1998. 

Both chlorines of 1,1-dichloroethylene (42) react stepwise with different 1-alkynes 43 and 44 to form the asymmetric enediyne 45 [34], The enediyne system 48 was prepared by Pd-catalyzed stereoselective hydrogenolysis of the 1,1-dibromo-l-alkene 46 with tin hydride to give 47, followed by coupling with 1-alkyne 23 in a one-pot reaction [35],... 

It is known that the reaction of 1,1-dibromo-l-alkenes with organostannanes affords internal alkynes [24]. The (chlorocyclopropyl)dienyne side chain 84 of callipeltoside A was prepared in 95% yield by the coupling of the 1,3-dienyl-stannane 82 with the dibromide 83. The use of DMF is important [38]. 

Reaction of dimethyl phosphonate (74) with the steroidal dienyl triflate 73 gave the dimethyl alkenylphosphonate 75 [23]. Dimethyl alkynylphosphonate (77) was produced in one step by the reaction of 1,1-dibromo-l-alkenes 76 with dimethyl phosphonate (74) in DMF using Pd(OAc)2-DPPF as a catalyst and propylene oxide as a scavenger of HBr. The expected monocoupling product, bromovinylphos-phonate, was not obtained [24]. Phosphonates 78 can be converted to arylphos-phines 79 by reaction with aryl Grignard reagents, followed by reduction with HSiCls [25]. 

Hayashi found that methylene-7r-allylpalladium 635 can be generated from 2-bromo-1,3-diene, which is prepared by the Pd-catalyzed cross-coupling of 1,1-dibromo-l-alkene 633 with vinylzinc reagent. Thus, the reaction of l-phenyl-2-... 

Another plausible altemative is the metal-catalyzed coupling of amides with alkynyl bromides or 1,1-dibromo-l-alkene [196]. Scheme 4.55 shows the more significant reported results with 2-pyrrolidine derivatives. ... 

Since the yields are between low and moderate with (bromoethynyl)benzene and, in the case of 1,1-dibromo-l-alkene, a decreased in the yield is observed with electron-donating groups on the phenyl ring, we anticipated a low conversion when R = indole. Therefore, we decided to dismiss this approach at this point. 

Yin, N. Wang, G. Qian, M. Negishi, E. I. 2006. Stereoselective synthesis of the side chains of mycolac-tones A and B featuring stepwise double substitutions of 1,1-dibromo-l-alkenes. Angew. Chem. Int. Ed. 45 2916-2920. 

Bauer, A. Miller, M. W. Vice, S. F. McCombie, S. W. 2001. Suzuki arylation of 1,1-dibromo-l-alkenes Synthesis of tetra-substituted alkenes. Synlett 254—256. 

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