Alkene formation stereochemistry

Monocyclic Phosphoranes. - Further studies on the mechanism and stereochemistry of the Wittig reaction have been conducted by a combination of 1H, 13C and 3 P n.m.r.2k 25. The results show that at -18°C both ois and trans diastereomeric oxaphosphetans (e.g. 17 and 18) may be observed and their decomposition to alkenes monitored by n.m.r. Evidence was presented to suggest that during this process oxaphosphetan equilibration involving the siphoning of (17) into (18) occurred in competition with alkene formation. 

Stannyl- (and -silyl-) carboxylic acids undergo oxidative decarboxylation with LTA under mild conditions to provide the corresponding alkenes. This represents an improvement on the well-known alkene-forming decarboxylation of acids with LTA, which requires thermtd or photochemical conditions, for example. The directing metal effect leads to improved yields and regioselectivity. However, stereo-specific alkene formation did not occur and this could imply free radical involvement or transmetallation (Pb for Sn) (stereochemistry ) followed by cation formation, see for example Scheme 27. 

Barton and coworkers developed a very useful procedure for the deoxygenation of alcohols, which involves conversion of the alcohol to the corresponding xanthate derivative followed by reaction with BuaSnH. When applied to the bis(xanthates) derived from v/ c-diols the reaction gives alkenes, as illustrated in equation (17). Once again alkene formation is independent of the stereochemistry of the starting diols. 

Little is known about the stereochemistry of trisubstituted alkene formation in the Julia alkenation. In a synthesis of milbemycin 33 Barrett and coworkersgenerated intermediate (91 equation 22) as a mixture of isomers (E Z = 5 3) by reductive elimination of a 3-acetoxy sulfone however, a similar reductive elimination on the 3-hydroxy sulfone shown in equation (23) gave a single isomer. The marked difference in the yield of these two transformations reflects the advantage of suppressing the retroaldoliza-tion reaction by acylation. 

A disadvantage of this procedure is that reductive cleavage of the epoxy sulfones leading to trisub-stituted alkenes, e.g. (95), is not stereoselective. However, formation of disubsituted alkenes follows the trends found in the standard Julia alkenation in that rrani-alkenes are favored (equation 24) and proximate branching increases the stereoselectivity (equation 25). Unlike the standard Julia alkenation, the stereochemistry of the epoxy sulfone reductive elimination depends on the stereochemistry of the precur-... 

The Cope elimination has been used to synthesize a variety of acyclic alkenes. 1,2-Disubstituted acyclic alkenes are usually obtained with the ( )-stereochemistry because of steric hindrance to (Z)-alkene formation. The stereochemistry of trisubstituted alkenes is determined by the configuration of the starting amine oxide and is not usually affected by subsequent isomerization. ... 

The stereochemistry of trisubstituted alkene formation was demonstrated by Kingsbury and Cram who found that the ctyr/iro-sulfoxide (37) gave mainly the ( )-alkene (38 equation 19) with the (Z)-alkene (40 equation 20) being the major product from thermolysis of the r/treo-sulfoxide (39). The rate and stereochemistry of elimination was found to be independent of solvent, and so the concerted syn elimination mechanism outlined in equation (21) was proposed. The variation of the -deuterium isotope effect with temperature is consistent with a linear hydrogen transfer, and the elimination has been found to be reversible, with sulfenic acids being trapped both inter- and intra-molecularly by addition to alkenes to give sulfoxides (Schemes 2 and... 

As with amine oxides and sulfoxides, acyclic 1,2-disubstituted alkenes are usually obtained with the ( )-stereochemistry, although the formation of a,(3-unsaturated nitriles is reported to give a mixture of ( )- and (Z)-isomers. For cyclic alkenes, the stereochemistry of double bond formation depends upon ring size. However, it can be affected by conformational factors, e.g. cyclododecyl phenyl selenide gives a mixture of cis- and fra/is-cyclododecenes on oxidative elimination (equation 38) but only the (El-isomer (101) was obtained from the acetoxycyclododecyl selenide (100 equation 39). ... 

In the reaction of a phosphonium ylide with an aldehyde or ketone, a mixture of E- and Z-alkenes can result. In general, it is found that a resonance-stabilized ylide gives rise predominantly to the fJ-alkene, whereas a non-stabilized ylide usually gives more of the Z-alkene. The stereochemistry of the alkene product must arise from the stereochemistry of the oxaphosphetane, as the second step (the breakdown of the oxaphosphetane) takes place by way of a concerted syn elimination. Therefore, of the two diastereomeric oxaphosphetanes, the cis isomer leads to the Z-alkene and the trans isomer to the E-alkene (2.73). With a non-stabilized phosphonium ylide, the formation of the oxaphosphetane is thought to be irreversible. Therefore the Zr-E ratio is a reflection of the stereoselectivity in the first, kinetically controlled step. The preference for the formation of the cis oxaphosphetane has been attributed to the minimized steric interactions in the transition state involving orthogonally aligned reactants. 

Although not all Wittig reactions proceed by exactly the same mechanism, an oxa-phosphetane intermediate is common to all of the mechanisms (Scheme 2). TTie overall rates of the reactions depend upon the rates of formation of the oxaphosphetane and of its conversion to alkene and phosphine oxide. The stereochemistry of alkene formation depends on the rates of formation and conversion to product of the stereoiso-meric oxaphosphetanes, and upon equilibration of the oxaphosphetane with starting materials and with zwitterionic intermediates in some cases f3-5k... 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

A significant modification in the stereochemistry is observed when the double bond is conjugated with a group that can stabilize a carbocation intermediate. Most of the specific cases involve an aryl substituent. Examples of alkenes that give primarily syn addition are Z- and -l-phenylpropene, Z- and - -<-butylstyrene, l-phenyl-4-/-butylcyclohex-ene, and indene. The mechanism proposed for these additions features an ion pair as the key intermediate. Because of the greater stability of the carbocations in these molecules, concerted attack by halide ion is not required for complete carbon-hydrogen bond formation. If the ion pair formed by alkene protonation collapses to product faster than reorientation takes place, the result will be syn addition, since the proton and halide ion are initially on the same side of the molecule. 

E) alkenes. One explanation for this is that the reaction of the ylid with the carbonyl compound is a 2-1-2 cycloaddition, which in order to be concerted must adopt the [rt2s+n2al pathway. As we have seen earlier (p. 1079), this pathway leads to the formation of the more sterically crowded product, in this case the (Z) alkene. If this explanation is correct, it is not easy to explain the predominant formation of ( ) products from stable ylids, but (E) compounds are of course generally thermodynamically more stable than the (Z) isomers, and the stereochemistry seems to depend on many factors. 

In 1995, and regrettably missed in last year s review, Klotgen and Wiirthwein described the formation of the 4,5-dihydroazepine derivatives 2 by lithium induced cyclisation of the triene 1, followed by acylation <95TL7065>. This work has now been extended to the preparation of a number of l-acyl-2,3-dihydroazepines 4 from 3 <96T14801>. The formation of the intermediate anion and its subsequent cyclisation was followed by NMR spectroscopy and the stereochemistry of the final product elucidated by x-ray spectroscopy. The synthesis of optically active 2//-azepines 6 from amino acids has been described <96T10883>. The key step is the cyclisation of the amino acid derived alkene 5 with TFA. These azepines isomerise to the thermodynamically more stable 3//-azepines 7 in solution. 

Ketenes are especially reactive in [2 + 2] cycloadditions and an important reason is that they offer a low degree of steric interaction in the TS. Another reason is the electrophilic character of the ketene LUMO. As discussed in Section 10.4 of Part A, there is a large net charge transfer from the alkene to the ketene, with bond formation at the ketene sp carbon mnning ahead of that at the sp2 carbon. The stereoselectivity of ketene cycloadditions is the result of steric effects in the TS. Minimization of interaction between the substituents R and R leads to a cyclobutanone in which these substituents are cis, which is the stereochemistry usually observed in these reactions. 

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