Stereospecific Synthesis of Alkenes by Eliminative Cross‐Coupling of Enantioenriched sp³‐Hybridized Carbenoids

Abstract

1-Aryl-1,2-dialkylethenes were generated by a sequence of electrophilic substitution, 1,2-metalate rearrangement, and β-elimination initiated by the addition of enantioenriched α-(carbamoyloxy)alkylboronates to enantioenriched lithiated carbamates. The carbenoid stereochemical pairing [i.e., "like"=(S)+(S) or "unlike"=(S)+(R)] and the elimination mechanism (syn or anti), not substituent effects, determined the configuration of the trisubstituted alkene target. For example, (Z)-2,5-diphenyl-2-pentene was produced in 70 % yield with E/Z=5:95 by a like combination of Li and B carbenoids and syn (thermal) elimination whereas the E isomer was obtained in the same yield with E/Z>98:2 by an otherwise identical process involving an unlike stereochemical pairing. The concept elaborated overcomes an intrinsic limitation of traditional strategies for direct connective alkene synthesis, which cannot realize meaningful stereochemical bias unless the alkene substituents are strongly differentiated.

Formation of Olefins by Eliminative Dimerization and Eliminative Cross‐Coupling of Carbenoids: A Stereochemical Exercise

“…Stereospecific trisubstituted alkene synthesis by eliminative cross-couplingofLi-and B-based carbenoids involving anti-mode elimination.C bO = i-Pr 2 NCO 2 ,B pin = B(OCMe 2 CMe 2 O). [74] Scheme 21. Stereospecific trisubstituted alkene synthesis by eliminative cross-coupling of Li-and B-based carbenoidsi nvolving syn-mode elimination.C bO = i-Pr 2 NCO 2 ,B neo = B(OCH 2 CMe 2 CH 2 O).…”

“…[73] Although not conducted with the intention of making alkenes,t he findings of Matteson et al underscore the feasibility of as tereospecific olefin-forming cross-coupling reaction based on the combination of two different enantioenriched carbenoids.S uch ap rocess,w hich likewise exploits the differential reactivity of lithium-and boronbased carbenoids,w as successfully developed and recently disclosed by Blakemore and co-workers (Schemes 20 and 21). [74] Them ethod hinges on eliminative cross-coupling of an ucleophilic lithiated carbamate (e.g. 116)w ith an electrophilic a-carbamoyloxyboronate (e.g.…”

“…Depending on the reaction conditions employed and the kind of boronic ester used, the Blakemore alkene synthesis can be terminated by either an anti-orasyn-mode elimination step.For example,addition of boron carbenoid (S)-117 [31] to ap re-generated solution of lithium carbenoid (S)-116 in diethyl ether gave the putative ate complex lk-118,w hich rearranged upon warming to give the pre-elimination adduct lk-119 as essentially as ingle isomer (Scheme 20). [74] That the 1,2-metalate rearrangement of lk-118 was regioselective in this case (of the two potential OCb nucleofuges,t he benzylic OCb group was lost preferentially over its non-benzylic counterpart) is not ag eneral requirement, since either of the two possible rearrangement products would go on to generate the same alkene (see Scheme 14). Subsequent treatment of lk-119 with sodium methoxide resulted in an anti-mode elimination to give trisubstituted alkene 120 with high stereoselectivity and favoring the E configuration, as expected for the chosen like stereochemical pairing and anti elimination.…”

“…Stereospecific trisubstituted alkene synthesis by eliminative cross-coupling of Li-and B-based carbenoidsi nvolving syn-mode elimination.C bO = i-Pr 2 NCO 2 ,B neo = B(OCH 2 CMe 2 CH 2 O). [74] inative coupling follows the expected course.H owever, the intervention of noncanonical mechanisms cannot be discounted in scenarios where carbenoids possess unusual features that may allow for reactivity that deviates from the norm. Interesting cases in point are eliminative dimerization and eliminative cross-couplings involving 7-halo-7lithiobicyclo[2.2.1]hept-2-enes such as 40 and 83.T he true nature of norbornenyl carbenoids 40 and 83 is undoubtedly more complex than the simple covalent depictions shown in Schemes 7a nd 15 imply.…”

Enantiodivergent Synthesis of Allenes by Point‐to‐Axial Chirality Transfer

“…[10] Second, to obtain complete transfer of stereochemical information, the elimination process must proceed with very high stereospecificity. [11] The choice of vinylic leaving group (LG 1 )iscritical to controlling the selectivity in both of these key steps.W ewere attracted to selenium as we hoped that its relatively poor leaving group ability would enable it to act as aspectator group during the lithiation-borylation process and then, upon activation, to undergo elimination (Scheme 1C). Moreover,w eh ave recently shown that b-seleno boronic esters can undergo selective anti elimination in the presence of base or syn elimination upon oxidation to the corresponding selenoxide.…”