[75697-62-0] · C4H7LiO · 1-Lithio-1-methoxycyclopropane · (MW 78.05)
Solubility: sol THF, in which solvent it is prepared.
Preparative Methods: from 1-methoxy-1-phenylthiocyclopropane4 via reductive lithiation with Lithium 4,4´-Di-t-butylbiphenylide (LDBB) or Lithium 1-(Dimethylamino)naphthalenide (LDMAN) in THF at -78 °C.5 Alternatively, a similar reagent, 1-ethoxy-1-lithiocyclopropane, is obtained by lithium-tin and lithium-bromine exchange reactions of 1-ethoxy-1-(tri-n-butylstannyl)cyclopropane and 1-bromo-1-ethoxycyclopropane, respectively.6
1-Lithio-1-methoxycyclopropane reacts at -78 °C with aldehydes to give the expected addition products in high yields (eq 1).9
(1-Methoxycyclopropyl)alkyl alcohols are usually not isolated and the crude reaction products are directly subjected to acid-catalyzed rearrangement to 2-substituted cyclobutanones (eq 2).
From a synthetic point of view, preparation of 2-vinylcyclobutanones is the most interesting application of the above procedure. Several different sets of conditions have been elaborated to accomplish the rearrangement of the intermediate secondary or tertiary cyclopropylalkyl alcohols. In most cases, a solution of 48% aqueous Tetrafluoroboric Acid in THF or ether was found to be most effective.2 Vinylcyclobutanones are prepared from a,b-unsaturated aldehydes and ketones (eqs 3 and 4).10
In the case of acid sensitive molecules, the rearrangement can be conducted under neutral conditions by using Trifluoromethanesulfonic Anhydride in the presence of a hindered base, 2,6-di-t-butyl-4-methylpyridine (eq 5).5
2-Vinylcyclobutanones are important synthetic intermediates since they undergo ring expansion reactions under a variety of conditions. Thermal,5 acid catalyzed,3 alkoxide accelerated,11 or trimethylsilyl cyanide promoted12 rearrangements lead to the formation of five-, six-, and eight-membered ring systems.
Synthesis of 2-vinylcyclobutanones from 1-lithio-1-methoxycyclopropane rivals the method of Trost,13 which employs 1-lithio-1-phenylthiocyclopropane. In the latter method, substantial experimentation leading to different reaction conditions for each case is necessary to obtain good yields in the rearrangement step.4b
Cyclobutanones can also be prepared from 1-methylseleno-,14 1-phenylseleno-,14 and 1-bromocyclopropyllithium reagents15 (see 1-Bromo-1-lithio-2-phenylcyclopropane).
Harry M. Walborsky & Marek Topolski
Florida State University, Tallahassee, FL, USA