Arylthio-Metal Exchange of α-Arylthioalkanenitriles

Abstract

The addition of BuLi, Bu3MgLi, Et2ZnBuLi, or Me2CuLi to α-arylthioalkanenitriles triggers an arylthio-metal exchange. NMR spectroscopic analyses implicate organometallic attack on sulfur forming a three-coordinate sulfidate as the key intermediate. Electrophilic trapping affords tertiary and quaternary nitriles in high yield. The method addresses the challenge of improving the functional group tolerance and preventing polyalkylations.

Highly enantioselective metallation–substitution alpha to a chiral nitrile

“…To determine the absolute configuration of the sulfides, we carried out sulfur–magnesium exchange with i-PrMgCl. 16 This transformation has not to our knowledge been reported with an enantioenriched sulfide and it was intriguing to discover whether it would be possible to transfer chirality by this method. Addition of i-PrMgCl to the sulfide 5c in Et 2 O at –104 °C followed by addition of p -bromobenzoyl chloride gave the product 5g in moderate yield and only partial loss of enantioselectivity (Scheme 3).…”

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

“…Metalation strategies lie at the core of organic synthesis . Formation of metalated nitriles is illustrative of the different metalation strategies used to generate organometallics: traditional base‐promoted deprotonation ( 1 → 2 or 3 ; Scheme ), halogen–metal exchange ( 5 → 2 or 3 ), sulfoxide–metal exchange ( 6 → 2 or 3 ), and sulfide–metal exchange ( 7 → 2 or 3 ) . Each strategy has distinct advantages by providing selective access to either C‐metalated ( 2 ) or N‐metalated nitriles ( 3 ) which intrinsically control the chemo‐, regio‐, and stereoselectivity of alkylations .…”

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

“…[1] Formation of metalated nitriles is illustrative of the different metalation strategies used to generate organometallics:traditional base-promoted deprotonation (1!2 or 3;Scheme 1), [2] halogen-metal exchange (5!2 or 3), [3] sulfoxide-metal exchange (6!2 or 3), [4] and sulfide-metal exchange (7!2 or 3). [5] Each strategy has distinct advantages by providing selective access to either C-metalated (2)o rN -metalated nitriles (3)w hich intrinsically control the chemo-, [6] regio-, [3] and stereoselectivity of alkylations. [7] Conspicuously absent from the types of exchangeable functionality are sulfones such as 8.…”