Nickel‐catalyzed cross‐coupling reactions of bicyclo[1.1.0]butylmagnesium bromide and bicyclo[1.1.0]butyllithium derivatives with alkynyl chlorides and bromides

Abstract

Several alkynylbicyclo[1.1.0]butanes are prepared by coupling of bicyclo[1.1.0]butylmagnesium bromide with alkynyl chlorides. Severe side reactions, which take place with alkynyl bromides, are not observed. Bridgehead‐lithiated bicyclo[1.1.0]butanes are also effective components in these reactions. The coupling occurs by nickel catalysis as shown by control experiments, an uncatalyzed nucleophilic substitution at the acetylenic carbon atom not being a major reaction path. Alkyl‐ and aryllithium compounds could also be coupled with alkynyl chloride 13c, but in the case of alkynyllithium reagents side reactions decreased the synthetic value of this alkynylic coupling procedure.

Synthesis of 1,3-disubstituted bicyclo[1.1.0]butanes via directed bridgehead functionalization

“…1c). Previous work has shown that selective deprotonation of this position is possible, 12,35 and in specic tricyclic systems has been used for cross-coupling reactions, [36][37][38] however the use of this strategy for the general synthesis of 1,3-difunctionalized BCBs is, to our knowledge, unknown. Here we report the development of a directed metalation/Negishi cross-coupling 39,40 route to access these useful building blocks.…”

One-Pot Synthesis of Strain-Release Reagents from Methyl Sulfones

“…Some of these moieties are also found directly in natural products or utilized in medicinal chemistry for the introduction of bioisosteres . More specifically, sulfonyl-substituted BCB and housanes are exceptionally bench-stable and have found widespread applicability in strain-release cycloalkylation with either nucleophiles or radical species as well as in formal cycloaddition, where the resulting sulfonyl group serves as a handle for further derivatization (Scheme a, A ). − Moreover, in the case of BCB, their structure can be readily diversified via sulfone-directed C–H functionalization ( B ). ,,, While their superior versatility as strain-release reagents is well established, the general access to 1-sulfonylbicyclo[1.1.0]­butanes and housanes from inexpensive and readily available materials remains a challenge, typically requiring six steps and two purifications from sulfonyl chlorides in the case of BCB (Scheme b). ,,, As part of our research program directed at the elaboration and use of reagents of extreme strain such as cyclopropanones, we discovered that these strain-release reagents could be accessed in a streamlined manner via the formation of 3-sulfonylcyclobutanol intermediates susceptible to transannular ring-closure upon activation ( vide infra ). Herein, we report a general procedure for the preparation of 1-sulfonyl-bicyclo[1.1.0]­butanes in a single pot from readily available methyl sulfones and inexpensive epichlorohydrin (Scheme c).…”