C O M M U N I C A T I O N S
(not drawn)15 prior to reductive elimination to II-a. Presumably
magnesium alkoxide 12 is not able to achieve satisfactory bidentate
chelation (perhaps due preferential formation of higher aggregates),
and reductive elimination to III-a ensues.
Scheme 2. Mechanism for Reagent-Based Quadraselection
Formation of III-s is especially intriguing. Treatment of I with
Me2Zn in the presence of catalytic Li2CuCl4 was initially expected
to form III-a; however the product was clearly the syn-1,4-adduct
III-s. A tentative explanation posits that under the required “forcing”
reaction conditions (toluene, 12 h, 25 °C), epoxy vinylsulfone I
suffers SN2 anti-addition of chloride anion to giVe 10. While such
a species might undergo intramolecular 7-endotrig methylation to
III-s (possibly via a π-allyl intermediate), it is hard to argue that
such a process would be strongly favored over the intramolecular
5-exotrig alternative leading to II-s. However, oxidatiVe addition
of catalytic dimethylcuprate to 10 would be expected to afford 11
followed by reductiVe elimination to III-s. Apparently 11 like 12
does not benefit from bidentate chelation akin to 9, thus kinetically
favoring production of the distal allylic methylation product III-s
(Scheme 2). Additional experiments support the generation of allylic
chloride intermediates in the syn-methylation sequence.4
In conjunction with the recently reported 1,2-syn and 1,2-anti
additions to I2 this work provides the first example of a strategy
for reagent-controlled quadraselection, thus giving an enantiopure
collection of 16 stereotetrads from four enantiopure epoxyvinyl-
sulfones.
Supporting Information Available: Additional experimental details.
This material is available free of charge via the Internet at http://
pubs.acs.org.
ough screening of this reagent combination revealed that optimal
results were achieved by addition of trimethylaluminum (2.2 equiv)
to a -78 °C suspension of MeCu (1.0 equiv) followed by addition
of a solution of epoxyvinylsulfone I-3. The reaction was complete
after 2 h at -78 °C and 3 h at 25 °C. This 1,4-anti methylation
protocol worked exceptionally well for all substrates.12
Catalytic 1,4-anti methylations were surveyed using epoxyvi-
nylsulfone I-3 in the presence of 3 equiv of Me3Al and 0.09 equiv
of Cu[I]13 source (Li2CuCl4, LiMeCuCN or MeCu) to afford
adducts III-3a/III-3s with dr 14-17:1 in yields of 82-88% as
compared with dr >50:1 using Me3Al with stoichiometric MeCu
(Table 1). The Li2CuCl4 catalyzed Me3Al procedure was success-
fully applied to epoxides I-1, I-2, I-3, and I-4 although erosion of
diastereoselectivity was seen (Table 1, column 6).
Copper catalysis plays a prominent part in three of the four
reagent combinations employed to achieve the quadraselection
(Scheme 2). It is interesting to note that while the reaction of Me3Al/
MeCu or Me3Al/Li2CuCl4 with epoxyvinylsulfone family I gives
the expected14 SN2′ anti coupling product family III-a presumably
via intermediate 12, direct reaction of I with Me2CuLi generates
the alternative allylic regioisomer II-a. A tentative hypothesis for
the II-a/III-a regiocontrol may lie in the ability of the oxidolithium
moiety to stabilize proximal η-1 intermediate 9, by equilibrating
initially formed distal η-1 intermediate 8 via a π-allyl η-3 species
References
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(4) See Supporting Information.
(5) Upon the addition of Me2Zn to a solution of the epoxide and Li2CuCl4 in
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(6) In the case of I-3 and I-4, the solvent was a 24:1 mixture of toluene and
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