Organic Letters
Letter
relative to those in the minor diastereomer, presumably due to
shielding effects by the cis-oriented aromatic group. In
addition, protons corresponding to methyl groups in
dimethylsilyl products (i.e., 2b, 2d−2h) became inequivalent
due to the expected slow rotation induced by the bulky aryl
groups. We further confirmed the structure of compound 2c by
Scheme 7. Rearrangement of Substrates Bearing Electron-
Deficient Aryl Groups and 2-Naphthyl Derivative
We next evaluated dihydropyrans bearing alkyl substituents
at the migrating carbon (Scheme 6). These substrates
Scheme 6. Selective [1,4]-Wittig Rearrangement of
a
Center
On a last note, it is worth comparing the ability of
5
silyldihydropyrans 1 and isomeric 9a/b to undergo clean
rearrangements relative to the unsubstituted analogue 8
a
1
Diastereoselectivity determined by HNMR of the crude reaction
mixture.
underwent slow deprotonation under conditions A and B
(
see Scheme 4). However, addition of sec-butyllithium at −78
Figure 1. Comparison of yields and [1,4]-/[1,2]-selectivities of 1 vs 2-
silyl analogues 9a/9b and desilylated analogue 8.
°
C and warming to −10 °C (conditions C) allowed
deprotonation and rearrangement with excellent [1,4]-
in good yields, dihydropyran 8 reacts sluggishly to give a low
yield of [1,4]-Wittig product together with a complex mixture
of undetermined byproducts. On the other hand, the exclusive
selectivity. Dihydropyrans bearing PhMe Si groups on the 4-
2
position and n-propyl and cyclohexyl substituents at the
migrating carbon led to the corresponding silylcyclopropanes
[
1,4]-selectivity of 1 is independent of the nature of the silyl
2j and 2k in 83% and 76% yields, respectively. The n-propyl-
groups, while those of 9a or 9b are very sensitive to the sterics
of the silyl group.
substituted dihydropyran (1j) rearranged with higher diaster-
eoselectivity compared to the dihydropyrans bearing cycloalkyl
groups (Scheme 6). Interestingly, cyclopropyl-substituted
dihydropyrans 1l and 1m underwent rearrangement without
observable formation of the ring-opened products.
Dihydropyrans with electron-deficient aryl groups such as 1n
underwent Wittig rearrangements with flipped [1,4]-/[1,2]-
selectivity. Here, the predominant product was the [1,2]-Wittig
alcohol 3n (54%), followed by the [1,4]-silylcyclopropane 2n
In line with our previously proposed mechanistic hypothesis,
we maintain that the [1,4]-Wittig rearrangement of silyl
dihydropyrans proceeds primarily by a stepwise process
involving a homolytic C−O bond cleavage and intramolecular
5
radical/radical anion recombination (Scheme 8), a process
Scheme 8. Proposed Mechanism of the [1,4]-Wittig
Rearrangement of 4-Silyl-6-aryl(alkyl)-5,6-dihydroprans
(
4
17%) and a small amount of an isomeric [1,2]-Wittig product
n (6%). Formation of 4n indicates that benzylic deprotona-
tion becomes competitive when electron-deficient aryl groups
are present. Similarly, 2-pyridyl-substituted dihydropyran (1o)
predominantly afforded diastereomeric [1,2]-Wittig products
3
o and 3o′ (2:1 ratio), resulting from allylic deprotonation.
Unreacted 1o could not be isolated and instead underwent
oxidation during workup and purification to give lactone 5o.
16
7 −1
that must be faster than ∼7 × 10 s given that cyclopropyl-
17
Attempts to access the 4-pyridyl analogue using our established
route (Scheme 3) were unsuccessful due to reluctance of the
an (1p) failed to undergo Wittig rearrangement, and instead,
ring-opened products 6p and 7p were observed (Scheme 7).
bearing substrates did not lead to ring opened products. As
5
previously reported, the product distributions from 9a or 9b
suggest that increasing the steric demand of the silyl group
prevents [1,2]-recombination due to steric clash with the
phenyl group. These observations, together with the exclusive
[1,4]-selectivity displayed by 1 suggest that the [1,4]-/[1,2]-
5
726
Org. Lett. 2021, 23, 5724−5728
Mori-Quiroz, Luis M.
