Abstract
Intramolecular substitution in δ-halocarbanions leading to cyclobutanes is a relatively
slow process, thus they readily add to carbonyl groups; the thus-produced anionic
adducts cyclize to tetrahydropyran derivatives. A simple mechanistic discussion, optimization
of the reaction conditions, and scope of the reaction is presented.
Key words
aldol reactions - sulfones - halocarbanions - cyclizations - tetrahydropyrans
References
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The behavior of 1a and 1b without an electrophile under basic conditions [t -BuOK (2 equiv), THF, -50 °C or 0 °C, 1 h] revealed that, in contrast to γ-halocarbanions,
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The ratio of the diastereomers of 2a remains almost constant, in the range 1:0.55-1:0.70 (erythro /threo , according to 1 H NMR), during the course of the reaction.
erythro -isomer gave product 3a exclusively, while the threo -isomer gave a mixture of 3a /3b (9:1, according to 1 H NMR). This observation may lead to the conclusion, that erythro -isomer cyclizes relatively rapidly, while this process is slower for the threo -isomer and competitive retro-aldol reaction gives cross product 3b . The conformational preference for the cyclization of diastereomers of analogous
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In an independent experiment we performed the reaction of PhCHO (1 mmol), 4-MeOC6 H4 CHO (1 mmol), and 1b (1 mmol) under standard conditions to evaluate the effect of the relative electrophilicity
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<A NAME="RP00107SS-19">19 </A> During the optimization process, we observed that excess benzaldehyde (>1.25
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Reaction of 1c with benzaldehyde (-40 °C, 1 h) led to a mixture of the expected product 3f and uncyclized aldol-type adduct 2f (according to 1 H NMR analysis of the crude reaction mixture). To force the cyclization process the
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Probably due to the less favorable equilibrium of addition of stabilized enolate of
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