Synthesis of -Disubstituted Alkenes

The Zweifel trans-alkene synthesis from dialkyl-1-alkenylboranes involves the hy-droboration of 1-halo-l-alkynes with dialkylborane (Eq. 69) 126). It is of interest that the base produces a transfer with inversion 126 127). 

Protonolysis in the last step can also be achieved with aqueous silver ammonium nitrate for acid sensitive molecules as in a simple stereoselective route to prostaglandins (Eq. 70) 128 . 

Although trans-disubstituted olefins are readily prepared by the partial reduction of acetylenes with sodium in liquid ammonia M , this novel olefin synthesis via hydroboration has a unique advantage over the conventional method in which four consecutive stereocenters can be created in a predictable manner as shown by the following example (Eq. 71)U8). 

A more convenient procedure for the synthesis of ( )-alkenes has been reported 75). This involves the hydridation step with lithium aluminium hydride at 0 °C. The loss of thexyl group is also undesirable and it can be avoided by use of dibromoborane-dimethylsulfide (Eq. 73) 25 l22 . This procedure appears to be general for essentially all R groups with no disadvantages known. There is no loss of R groups. 

Both Z- and E-configurations of carbon-carbon double bond are an important structural moiety of insect pheromones. The synthesis of unsaturated alcohols has attracted considerable attention of organic chemists in recent years because such alcohols and their acetates are known to be insect sex attractants. Recently, a very convenient, general, one pot synthesis of Z alkenols132) and Z-alkenols 133) via organoboranes has been reported. 

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Various aspects of this reaction have been summarized by Kocienski.2 It is particularly useful for synthesis of disubstituted alkenes and conjugated dienes and trienes. It fails with some trisubstituted alkenes and most tetrasubstituted. alkenes because the precursors are unstable. One advantage of this route is that rra/is-alkenes are formed preferentially or exclusively. Yields are highest when the eliminated groups can adopt a /rons-coplanar arrangement. 

Scheme 5. General alkylidenation of esters to enol ethers 9 and synthesis of disubstituted ( )-alkenes 10 from aldehydes and chromium(II) reagents according to Takai and Utimoto.

Table 15 Synthesis of Disubstituted Alkenes by Trifluoroethyl Phosphonate Esters in THF...

For the synthesis of disubstituted alkenes by the Homer reaction, diere are general guidelines that can be followed to maximize selectivity, as shown in structure (246). It is best to have the larger of the two substituents of the double bond to be formed derived ffom the carbonyl moiety. This is particularly important if the substituent is anion-stabilizing since this will erode the selectivity at the elimination. These rules can be followed, regardless as to the stereochemistry of the alkene desired. 

The most common applications of the HWE reaction are in the synthesis of disubstituted ( )-alkenes. The stereoselectivity of the reaction can be maximized by increasing the size of the substituents on the phosphoryl portion. In cases where the stabilizing functionality is a caiboxy group, the size of the ester may be tuned to enhance ( )-alkene formation. 

U The Synthesis of ( )-Disubstituted Alkenes Comparison with the Wittig Reaction... 

In addition to Ni and Pd catalysts, Li2CuCU is also an effective catalyst for the coupling of alkenyl iodides with Grignard reagents. Since the stereochemistry of alkenyl iodides is also retained, the coupling reactions are useful for the stereoselective synthesis of disubstituted alkenes, - trisubstituted al-kenes, allylsilanes, allyl alcohols and tetrasubstituted alkenes (equations 25-29). ... 

Scheme 10.95 Synthesis of disubstituted alkenes by silver-catalyzed regioselective carbomagnesiation of arylalkynes [77].

Fig. 2 Synthesis of disubstituted alkenes by Fe-catalyzed reaction of tosylhydrazones with...

A modification of an earlier procedure for debromination of v/c-dibromides in the presence of catalytic amounts of diorganotellurides has allowed the synthesis of terminal alkenes and cis- and frani-l,2-disubstituted alkenes from appropriate precursors the relative substrate reactivities suggest that, as for the stoichiometric reaction, the catalytic reaction involves intermediate bromonium ion formation. The Te(IV) dibromides formed in the debrominative elimination are reduced back to the catalysts by either sodium ascorbate or the thiol glutathione. 

Alkene synthesis.9 The key step in the Julia synthesis of alkenes (11, 473-475) involves reductive elimination of a P-hydroxy sulfone with sodium amalgam. A recent modification involves elimination of a p-hydroxy imidazolyl sulfone with Sml2 (equation I).1 Both syntheses are particularly useful for preparation of disubstituted alkenes and conjugated dienes and trienes. Both methods of elimination favor formation of (E)-alkenes. In a direct comparison, a higher yield was obtained with Sml2 than with Na(Hg). 

Fig. 11.43. Claisen-Ireland rearrangement of two O-allyl-O-silyl ketene acetals. 7ran.v-sclective synthesis of disubstituted and E-selective synthesis of trisubstituted alkenes.

Application of the Wittig reaction of a nonstabilized ylide to the synthesis of an ( )-alkene is practically and effectively carried out by the Schlosser modification. Alternatively, the use of a trialkylphos-phonium ylide can produce high ratios of ( )-alkene." Recently, Vedejs has developed a reagent using dibenzophosphole ylides (110) to synthesize ( )-disubstituted alkenes (111) fixnn rddehydes (equation 24). The initial addition of ylide occurs at -78 C, but the intermediate oxaphosphetane must be heated to induce alkene formation. The stereoselectivity in the process is excellent, particularly for aldehydes with branched substitution a to the reacting center. Both the ethyl and butyl yli s have b n utilized. 

The Homer reaction can be applied to the synthesis of trisubstituted alkenes. As in the case of HWE reactions, the yield obtained by adding a disubstituted phosphine oxide to an aldehyde is frequently higher than that obtained by adding an anion to a ketone. This methodology was applied to the synthesis... 

Acyclic 1,2-disubstituted alkenes from sulfoxide pyrolyses are obtained with the trans geometry because of increased torsional interaction in the transition state leading to the cis isomer (e.g. equation 22). The stereochemistry of tri- and tetra-substituted alkenes is determined by the stereochemistry of the precursor sulfoxides and is predictable on the basis of the syn elimination mechanism. In practice the stereospeciflc synthesis of such alkenes is limited by the availability of isomerically pure starting materials. 

Couplings between alkenyl chlorides and alkyl Grignard reagents are catalyzed best by nickel complexes,as exemplified by the synthesis of terminal alkenes, disubstituted alkenes, cyclic alkenes and a silylmethyldiene (equations 5-8),2 while Pd(PPh3)4 has also been claimed to be useful for a few... 

An example of the formation of disubstituted alkenes with E configuration by the Meer-wein-Eschenmoser variant is the synthesis of (24.S )-53e-stigmasta-7,22,25-triene-3/i-ol291 -293. 

Giirtler, C. and Buchwald, S.L. (1999) A phosphane-free catalyst system for the Heck arylation of disubstituted alkenes application to the synthesis of trisubstituted olefins. Chem. Eur. J., 5, 3107-12. 

Shimizu K, Takimoto M, Sato Y, Mori M (2005) Nickel catalyzed regioselective synthesis of tetrasubstituted alkene using alkylative carboxylation of disubstituted alkynes. Org Lett 7 195-197... 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

An alternative synthesis of (Z)-l-halo-l-alkenes involves hydroboration of 1-halo-l-alkynes, followed by protonolysis (246,247). Disubstituted ( )-and (Z)-a1keny1 bromides can be prepared from ( )- and (Z)-a1keny1 boronic esters, respectively, by treatment with bromine followed by base (248). 

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