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

686
Scheme 69 Scheme 70
Lithiated (E)- 394 and (Z)-allylphosphine oxides
396 and phosphonates yield, in a highly diastereoselective
manner, the corresponding 1,4-γ-syn-product,
e.g., (E)-tiglyl phosphinoxides 395 and the 1,4γ-anti-adduct,
e.g., (E)-angelyl phosphinoxides 397
upon reaction with 2-cyclopentenone (Scheme
69). 104,105,215 A trans-decalyl or trans-fused chairchair
transition state 398 is postulated. There is a
destabilizing influence of the methyl groups on the
normal “trans-fused chair-chair”-like extended transition
state resulting in access to “cis-fused boatboat”-like,
“cis-fused chair-chair”-like, and “transfused
boat-chair”-like transition states involving
planar lithiated reagents. The configuration at the
phosphorus atom determines the face selectivity of
the reaction of the lithiated carbanion with an
enantiofacial enone according to the transition state
model. 215 To obtain exclusive face selectivity, the
substituents (R 1 and R 2 , 398) additional to the allyl
group and attached to the stereogenic phosphorus
must have quite different steric requirements; the
small substituent, e.g., a phenyl group (R 1 ) Ph, 398),
exclusively adopts a pseudoaxial and the large substituent,
e.g., a tert-butyl group (R 2 ) t Bu, 398), a
pseudoequatorial disposition in the transition state. 216
Reaction of the chiral allylphospholidines 399 (R
) Me, i Pr) with R,�-unsaturated cyclic ketones gives
the 1,4-γ-addition to provide 400; replacing the
methyl group at the nitrogen with the isopropyl group
(R ) i Pr, 399) remarkably enhances the enantioselectivity.
217 In contrast, the diastereomeric phospholidines
401 gives poor diastereofacial selectivity and
form 1,4-γ-adducts 402 and 1,2-R-adducts 403 (Scheme
70). 217
Lithiated allylidenoxyphosphorane 404 is alkylated
and silylated at the R-position to give 405 and 406
(Scheme 71), whereby the reaction could involve a
direct C-silylation or a more likely O-silylation followed
by C-O rearrangement. 218a Thus, deprotonation
of 404 followed by addition of triisopropylsilyl
triflate (TIPS) yields an ester 406 as a mixture of two
P/CR-diastereomers due to migration of the methyl
group. This rearrangement has been applied to the
Scheme 71
syntheses of a squalene from farnesol. However,
application of chlorotrimethylsilane instead of TIPS
results in exclusive C-silylation (cf. 405).
Epoxides 408 are attacked by the lithiated anion
of allyldiphenylphosphine oxide 407 in 1,2-dimethoxyethane.
A boron trifluoride-diethyl ether complex
promoted ring-opening reaction and affords a mixture
of both R- 409 and γ- 410 products (Scheme 72).
When toluene is used as solvent, a pronounced
preference for γ-attack of the anion is observed. 218b
3. Chiral Phosphonamides (CdC−C−P(O)(NR)2)
Chiral phosphonamides are important precursors
for asymmetric synthesis and are therefore dealt with
in this separate section. The addition of tert-butyl
cinnamate 413 to crotylphosphonamide derivative
411 yields syn-416 and anti-417 γ-adducts in excellent
yield and high diastereoselectivity (ratio 92:8)
(Scheme 73). Similar behavior is shown by allyl-3,4-dihydro-4-oxo-(2H)-pyridine-1-carboxylate.
219,220 Consecutive
asymmetric Michael additions with cinnama-