Page 1193 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Another synthetic equivalent that has been extensively developed corresponds 1169
−
to the propanal “homoenolate,” CH CH CH = O. 13 This structure is the umpolung
2
2
equivalent of an important electrophilic reagent, the , -unsaturated aldehyde acrolein. SECTION 13.1
Scheme 13.2 illustrates some of the propanal homoenolate equivalents that have been Synthetic Analysis and
Planning
developed. In general, the reagents used for these transformations are reactive toward
electrophiles such as alkyl halides and carbonyl compounds. Several general points
can be made about the reagents in Scheme 13.2. First, it should be noted that they
all deliver the aldehyde functionality in a masked form, such as an acetal or enol
ether. The aldehyde is liberated in a final step from the protected precursor. Several
of the reagents involve delocalized allylic anions, which gives rise to the possibility
of electrophilic attack at either the -or -position of the allylic group. In most cases,
the -attack that is necessary for the anion to function as a propanal homoenolate is
dominant. In Entry 1, the 2-methoxycyclopropyllithium is used to form a cyclopropyl
carbinol. The methoxy group serves both to promote fragmentation of the cyclopropyl
ring and to establish the aldehyde oxidation level. In Entry 2, the lithiation product
of allyl methyl ether serves as a nucleophile and the aldehyde group is liberated by
hydrolysis. Entry 3 is similar, but uses a trimethylsilyl ether. In Entry 4, allylic lithiation
of an N-allylamine provides a nucleophile and can subsequently be hydrolyzed to the
aldehyde.
In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation
and is then reductively removed after alkylation. The reagent in Entry 6 is prepared
by dilithiation of allyl hydrosulfide using n-butyllithium. After nucleophilic addition
and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry
7 uses the epoxidation of a vinyl silane to form a -hydroxy aldehyde masked as
a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl
groups containing aldehydes masked as acetals.
The concept of developing reagents that are the synthetic equivalent of inacces-
sible species can be taken another step by considering dipolar species. For example,
structures B and C incorporate both electrophilic and nucleophilic centers. Such
reagents might be incorporated into ring-forming schemes, since they have the ability,
at least formally, of undergoing cycloaddition reactions.

O
_ +
C H OCCHCH CH
2
2
–
2 5
CCH CH 2 +
2
O
B C
Among the real chemical species that have been developed along these lines are the
cyclopropyl phosphonium ions 1 and 2.

Ph P + CO C H Ph P + SPh
3
3
2 2 5
1 2

13
For reviews of homoenolate anions, see J. C. Stowell, Chem. Rev., 84, 409 (1984); N. H. Werstiuk,
Tetrahedron, 39, 205 (1983).