Carbenoid Chain Reactions:  Substitutions by Organolithium Compounds at Unactivated 1-Chloro-1-alkenes

Abstract

The deceptively simple "cross-coupling" reactions Alk(2)C=CA-Cl + RLi --> Alk(2)C=CA-R + LiCl (A = H, D, or Cl) occur via an alkylidenecarbenoid chain mechanism in three steps without a transition metal catalyst. In the initiating step 1, the sterically shielded 2-(chloromethylidene)-1,1,3,3-tetramethylindans 2a-c (Alk(2)C=CA-Cl) generate a Cl,Li-alkylidenecarbenoid (Alk(2)C=CLi-Cl, 6) through the transfer of atom A to RLi (methyllithium, n-butyllithium, or aryllithium). The chain cycle consists of the following two steps: (i) A fast vinylic substitution reaction of these RLi at carbenoid 6 (step 2) with formation of the chain carrier Alk(2)C=CLi-R (8), and (ii) a rate-limiting transfer of atom A (step 3) from reagent 2 to the chain carrier 8 with formation of the product Alk(2)C=CA-R (4) and with regeneration of carbenoid 6. This chain propagation step 3 was sufficiently slow to allow steady-state concentrations of Alk(2)C=CLi-Aryl to be observed (by NMR) with RLi = C6H5Li (in Et2O) and with 4-(Me3Si)C6H4Li (in t-BuOMe), whereas these chain processes were much faster in THF solution. PhC[triple bond]CLi cannot perform step 1, but its carbenoid chain processes with reagents 2a and 2c may be started with MeLi, whereafter LiC[triple bond]CPh reacts faster than MeLi in the product-determining step 2 to generate the chain carrier Alk(2)C=CLi-C[triple bond]CPh (8g), which completes its chain cycle through the slower step 3. The sterically congested products were formed with surprising ease even with RLi as bulky as 2,6-dimethylphenyllithium and 2,4,6-tri-tert-butylphenyllithium.

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants§

“…However, the idea that 24 might have been generated from 6 via 20 (and the dichloro alcohol 5 ) had to be dismissed: Although an authentic [3] sample of 5 was quickly consumed under the above conditions of hydrolyzing 6 , it furnished none of 24 , 23 or 10 . Nevertheless, 24 accumulated in the last period of transforming 6 into 10 (>15 hours at or above 100 °C); such a late appearance of 24 may be caused by a slowly emerging precursor (other than 5 ).…”

“…(i) With respect to repulsive strain, an attempted protonation of the alkoxide 2 immediately after its generation [2] at −70 °C failed to provide 1 , because 2 cyclized too rapidly with formation of the chlorooxirane 3 . On the other hand, the somewhat alleviated internal repulsion in alkoxide 4 allowed it to be trapped by protonation below −10 °C before the cyclization could interfere [3], so that the resultant alcohol 5 could be isolated (crude yield 90% from 1,1,3,3-tetramethylindan-2-one) and dehydrated to give 2-(dichloromethylidene)-1,1,3,3-tetramethylindane ( 6 ) as the only product (97% yield). (ii) In X-ray diffraction analyses [4–9], the 1,1,3,3-tetramethylindan-2-ylidene parts turned out to be rather rigid, except for an occasional folding along the C-1/C-3 axis, and they did not exhibit the structural disorder problems and vexing angular flexibility which can arise with the t- Bu 2 C groups exemplified in Scheme 1.…”

“…(iv) Vinylic nucleophilic substitution (S N V) of the chloride anion from 6 by even a very strong nucleophile R–Mt (Mt = alkali metal) to give 7 may appear problematic, because the first intermediate 9 expected with the usual ARE (addition–rotation–elimination) [12] mechanism would suffer from poor stabilization of the negative charge at C-2 which is flanked by two tert -alkyl groups. Instead, the substitution products 7 were obtained from 6 in THF via the cyclic Li,Cl-carbenoid 8 at room temperature (rt) by the carbenoid chain mechanism [3], as indicated in the bottom line of Scheme 1. These S N V reactions proceed properly because 8 has a reduced (albeit not vanishing) inclination toward cycloalkyne formation through the Fritsch–Buttenberg–Wiechell (FBW) rearrangement [13], whereas S N V reactions of acyclic Mt,Hal-carbenoids often have to compete with FBW processes forming acyclic alkynes.…”

Versatile Bisethynyl[60]fulleropyrrolidine Scaffolds for Mimicking Artificial Light‐Harvesting Photoreaction Centers

“…The synthesis of ketone 42 started with the synthesis of iodophenyl-phenothiazine 38, which was prepared by following the protocols reported in the literature, [54,55] except for the Pd-catalyzed cross-coupling reaction, which was performed under microwave conditions (see the Supporting Information). Molecule 38 was coupled to TMSA (39) and converted into aldehyde 40 by successive deprotection (10) and lithiation exchange reaction with nBuLi followed by addition of DMF.…”

A DFT Study on the Mechanism of Samarium (II)-catalyzed Cyclopropanation Synthesis with α,β -unsaturated Carboxylic Acids, Alcohols and Amides

“…Since the reported use of diiodomethane and a Zn/Cu couple to react with olefins to form cyclopropane units by Simmons and Smith, the cyclopropanation reaction were catalyzed by transition metals to form active reagents similar to the SimmonsSmith reagent that can make cyclopropane-containing products from olefins with high efficiency and stereoselectivity. To our best knowledge, many transition metals such as Rh, Ru, Pd, Pt, Ni, Cu, Zn, Sm, Al and Li are found to be able to catalyze cyclopropanation via a metal-carbene complex [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Zhao and co-workers have studied the reaction mechanism of samarium (II) carbenoid promoted cyclopropanation reaction with ethylene and the effect of THF solvent [34].…”