Regioselectivity of the Reactions of Heteroatom-Stabilized Allyl ...

684
Scheme 61
Scheme 62
61). 197 However, the 2-hydroxyalkylphosphonates 347
are not always effective precursors for the dienes 350
if other functional groups stabilizing the diene are
missing. 200 The reaction of the anion of 346 with
ketones usually gives R-products 348, 201 but with
benzophenone the γ-product 349 is formed exclusively
and acetophenone yields a mixture of both Rand
γ-isomers under conditions of kinetic control at
-78 °C (Scheme 61).
Furthermore, the extent of the formation of R-products
348 vs γ-products 349 depends critically on the
substrate’s structure and is influenced by steric
interactions. 202 The latter plays a role in the reaction
with benzaldehyde, in which the γ-selectivity is
increased with the increase of steric hindrance of the
phosphoryl group. 203 Thus, γ-selectivity is observed
for the O,O-di-tert-butylphosphoryl group where 351
gives 352 (Scheme 62). Treatment of allylic phosphonates
with various para-substituted benzaldehydes
shows the further dependence of the regioselectivity
on the nature of the electrophile: while in general
R-product 348 is observed, γ-attack 349 occurs in the
reaction with p-nitrobenzaldehyde. 204
In addition, increasing the reaction temperature
to favor thermodynamic control can have a dramatic
effect on the composition of the reaction products.
Beside the R- 348 and γ-products 349, δ-ketoalkylphosphonate
355 (Scheme 63) is now formed as the
main product resulting from the reaction of the
lithium enolate 353 with the isomerized vinylic
phosphonate 354. However, in case of benzophenone
Scheme 63
Scheme 64
the “thermodynamic” product was identical to the
“kinetic” γ-product 349. 205
Allylphosphonates 357 react smoothly with R,�unsaturated
ketones, but the reaction course depends
on the structure of the carbonyl substrate. Thus, the
configurationally constrained (Z)-unsaturated ketone
coumarin 360, adds at the γ-carbon to give 361 (Eisomer),
whereas but-3-en-2-one 358 affords the
R-adduct 359 (Scheme 64). 206
The reaction of �-substituted cyclic and acyclic R,�unsaturated
ketones, e.g., 362 which bear an enolizable
R′-hydrogen and no leaving group in position �
involves an annulation to afford a cyclohexanone
derivative 364 via 363 and 365 (Scheme 65). 206
Similar to sulfoxides (section II.C.3) and phosphine
oxides (section II.F.2), reaction with enones occurs
by 1,4-γ-addition products to give intermediates
363. 104,105
Strict R-regioselectivity is observed in the reaction
of lithiated 369 with ethyl formate (Scheme 66) or
ethyl chloroformate to give 370, or a mixture of 370
with its tautomeric aldehyde 367, or the conjugated
aldehyde 368 due to prototropy of the enol 370 (R 1 )
R 2 ) H). The product 370 can be transformed into
the corresponding stable O-acetylated 371 and Osilylated
372 derivatives which are stabilized by the
silicon substituent. 207 Steric hindrance due to the
trimethylsilyl group at the R-position of 369 (X )
SiMe3) results in strict γ-regioselectivity, giving the
1-(E)-2-phosphonodienol 366 in high yield with excel-