Cyclic Nitriles:  Diastereoselective Alkylations

Abstract

[reaction: see text] Diastereoselective alkylations of metalated conformationally locked 4-tert-butylcyclohexanecarbonitrile are highly diastereoselective with magnesium and copper counterions but only modestly diastereoselective with lithium as the counterion. Selective generation of diverse metalated nitriles is readily achieved through bromine-magnesium, -copper, and -lithium exchange reactions of the corresponding bromonitrile or, for lithium, by deprotonating the parent nitrile with lithium diethylamide. Collectively, high alkylation stereoselectivities correlate with the retentive alkylations of C-metalated nitriles, whereas N-lithiated nitriles alkylate with modest selectivity, reflecting minimal steric differences in the corresponding axial and equatorial electrophile trajectories.

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

“…Alkylations are efficient with activated (entries 1–2, 7, and 9–14) and unactivated alkyl halides (entries 3 and 15), diphenyl disulfide (entry 4), methyl cyanoformate (entries 5, 8), and 2‐chloropyridine (entry 6), a challenging electrophile for metalated nitrile arylation . Allylation of the conformationally constrained cyclohexanecarbonitrile 15 c afforded an 11.3:1 ratio of axial to equatorial nitriles ( 4 h ; entry 7), a stereochemical outcome consistent with alkylation by an equatorial magnesiate …”

Stereoselective SE2′ Protonation of α‐Hydroxyallylsilanes Mediated by a Brook Rearrangement

“…This means that the overall process is equivalent to trapping of an enantioenriched C-chiral a-nitrile carbanion, which has a very low inversion barrier, [11,12] in up to 77 % ee with the aid of both the concerted process of the protonation and a carbamoyl group. [13] Experimental Section A solution of tBuOLi (0.5 m in tBuOH, 14.8 mL, 0.0074 mmol) was added to a solution of (Z)-7 (50.4 mg, 0.148 mmol) in tBuOH (1.7 mL) at 25 8C.…”

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

“…Alkylations are efficient with activated (entries 1-2, 7, and 9-14) and unactivated alkyl halides (entries 3a nd 15), diphenyl disulfide (entry 4), methyl cyanoformate (entries 5, 8), and 2-chloropyridine (entry 6), ac hallenging electrophile for metalated nitrile arylation. [21] Thes ulfone-metal exchange of 15 h and 15 i are an intriguing pair (Table 1, entries 14 and 15). [21] Thes ulfone-metal exchange of 15 h and 15 i are an intriguing pair (Table 1, entries 14 and 15).…”

“…[19] Allylation of the conformationally constrained cyclohexanecarbonitrile 15 c [20] afforded an 11.3:1 ratio of axial to equatorial nitriles (4h;e ntry 7), as tereochemical outcome consistent with alkylation by an equatorial magnesiate. [21] Thes ulfone-metal exchange of 15 h and 15 i are an intriguing pair (Table 1, entries 14 and 15). Exposure of 15 h to BuLi afforded al ithiated nitrile which underwent alkylation with benzyl bromide to afford 4o rather than engaging in a4 -exo-tet cyclization, presumably because of the unfavorable trajectory involved in forming am ethylene cyclobutane (entry 14).…”