58th Annual Report on Research 2013 Under Sponsorship of the ACS Petroleum Research Fund

Samarium diiodide is one of the most useful reagents employed by organic chemists.  The use of this reagent is greatly enhanced by the addition of electron rich cosolvents.  HMPA (1) is the most common cosolvent to be employed and the majority of modern SmI₂ chemistry is accomplished with this cosolvent.  Unfortunately HMPA is a mutagen which has lead to an extended search for suitable alternatives.  The goals of this work are to find SmI₂ activators which are both safer and more effective.  We have recently reported that TPPA (2) is approximately an order of magnitude better at activating SmI₂ at two of its key synthetic processes, reduction of carbon-halogen bonds and reduction of ketones.  Our most recent work involves the use of deprotonatable phosphoramides such as DPMPA (3).  It is thought that the conjugate base of 3 will deliver even more electron density to the metal center and produce a more reactive complex.

Compound 3 can be synthesized in multi-gram quantities via a two-step procedure using POCl₃.  Upon treatment of a THF solution of DPMPA with BuLi and exposure to SmI₂, a deep brown (not violet) solution with powerful reductive capabilities is obtained.

The reduction of the reluctant radical precursor 1-chlorodecane was used as an assay for the relative reactivities of various SmI₂/activator complexes.  As can be seen in Table 1, SmI₂/DPMPA^- complexes of ratios 1:2, 1:3, and 1:4 are dramatically more reactive than other synthetically useful SmI₂ complexes.  Neutral phosphoramides (HMPA, diHMPA, TPPA, DPMPA) and SmI₂/H₂O/Et₃N produce yields of 0-1% of decane under these very mild and dilute conditions.  By contrast, the complex SmI₂/4 DPMPA^- affords a 90% yield of decane after one minute.

Table1.  The Reduction of 1-Chlorodecane with SmI₂ and Additives

The 4:1 complex of DPMPA^- and SmI₂ has been used to reductively cyclize a group of haloalkenylnaphthalenes 4a-d as shown in Table 2.  It has been determined that the best approach for these cyclizations involves the slow addition of SmI₂ to a cold THF solution of substrate plus DPMPA^- (Method B).  These conditions minimize formation of the reduced uncyclized product 5 and naphthalene.  The optimal temperature for this addition depends on the radical precursor.  The more reactive bromides react smoothly at a starting temperature of -66^oC.  The less reactive chlorides work better at warmer temperatures.  Cyclization of chlorobutenyl substrate 4d works best at a starting temperature of -23^oC.

We have also characterized SmI₂/ DPMPA^- complexes by visible spectroscopy and cyclic voltammetry.  Samarium diiodide in THF has absorption maxima at 553 and 621 nm and is blue in color.  Neutral phosphoramides such as HMPA or TPPA produce a violet solution with a broad band centered at 540 nm.  Addition of four equivalents of DPMPA^- to SmI₂ affords a brown solution with an absorption maximum at 405 nm.  Cyclic voltammetry was used to attempt to quantify the reducing power of SmI₂/ DPMPA^- complexes.  Samarium diiodide in THF has a standard potential of -1.33 V vs. Ag/AgNO₃.  Addition of two equivalents of DPMPA^- to SmI₂/THF affords a solution with a standard potential of -1.93 V, very close to the value of SmI₂/4 HMPA (-2.07 V) and the more reactive SmI₂/4 TPPA (-1.94 V).  Instrumental limitations prevent the measurement of standard potential for SmI₂/3 DPMPA^- and SmI₂/4 DPMPA^- . 

Table 2.  The Reductive Cyclization of Haloalkenyl Naphthalenes.

Current work in this laboratory focuses on the use of other reluctant radical precursors, as well as the development of new SmI₂ activators.