The carboboration of Me 3 Si-substituted alkynes and allenes with boranes and borocations.

The 1,1-carboboration of 1-Me 3 Si-1-alkynes is the dominant reaction observed using PhBCl(2-DMAP)][AlCl 4 ], 1 , and PhBCl 2 electrophiles, with highly substituted vinyl pinacol boronate esters isolated post esterification. Other aryl and heteroaryl congeners of both 1 and PhBCl 2 have a limited scope in the 1,1-carboboration of 1-Me 3 Si-1-alkynes, with desilylboration more prevalent. PhBCl 2 converts Me 3 Si-substituted allenes to allylboranes via a formal 1,3-carboboration with Me 3 Si-migration. [Cl 2 B(2-DMAP)][AlCl 4 ] reacted with a number of 1-Me 3 Si-1-alkynes by desilylboration, whilst with 1-Me 3 Si-ethyne a 1,1-boroamination reaction proceeds, which with excess boron electrophile is followed by an intermolecular desilylboration to form a tricationic-borate. The use of excess 1-Me 3 Si-1-propyne relative to 1 (and a thienyl congener of 1 ) formed 2-boradienes in low yields from the reaction with two equivalents of alkyne. Vinyl borocations ligated by 2,6-lutidine of the general formula, [(vinyl)BCl(2,6-lutidine)][AlCl 4 ] formed 1-boradienes with 1-Me 3 Si-1-alkynes. ArylBCl and aryl and containing borocations synthesised by electrophilic borylation effect the carboboration of TMS-substituted alkynes and allenes.


Introduction
The 1,1-carboboration of alkynes has received increased interest in recent years following the discovery of the 1,1carboboration of terminal and internal alkynes with the strong electrophile RB(C 6 F 5 ) 2 (R = C 6 F 5 , alkyl). 1 Addition of RB(C 6 F 5 ) 2 to a terminal alkyne induces a 1,2-shift of H (or a hydrocarbyl for internal alkynes) along the alkynyl backbone with subsequent migration of the R group from boron to carbon resulting in 1,1carboboration. 2 This reaction has been developed into a useful route to arylboranes by benzannulation, 3 and to highly substituted vinyl boranes that are complementary to those obtained from hydroboration. 4 1,1-carboboration was pioneered by Wrackmeyer albeit with weaker boron electrophiles, such as trialkylboranes, for the 1,1carboboration of activated alkynes, e.g., alkynes substituted with heavier group 14 substituents (Scheme 1, top). 5 Wrackmeyer and co-workers reported extensively on this topic and determined the relative reactivity of a range of substituted alkynes toward BEt 3 to be R 3 Pb > R 3 Sn > R 3 Ge > R 3 Si (TMS), with R 3 C-substituted alkynes not amenable. 5 These studies predominantly used trialkylboranes; in contrast, the utilisation of vinyl and aryl boranes (excluding B(C 6 F 5 ) 3 ) for the 1,1-vinylboration or 1,1-aryl-boration of alkynes is rare with only limited examples reported using BPh 3 or PhB(C 6 F 5 ) 2 . 6,7 One report particularly relevant to this work showed that Ph 2 BX (X = Cl or Br) effected the 1,1-carboboration of 1-TMS-1-hexyne (Scheme 1, top). 8 It should be noted that with (chloro) x (aryl) 3-x B compounds TMS substitution appears essential for 1,1carboboration, with PhBCl 2 and terminal alkynes reacting via 1,2-halo-or 1,2-carbo-boration instead. 9 To the best of our knowledge the outcome from combining TMS-alkynes and (hydrocarbyl)BCl 2 has not been reported to date. Scheme 1: Relevant early 1,1-carboborations and the approach in this work We envisaged combining arene borylation, 10 or alkyne haloboration, 11 using BCl 3 derived borocations (to produce arylBCl 2 and [vinylBCl(amine)] + , respectively) with 1,1carboboration to generate synthetically useful highly substituted vinyl (or dienyl) boronate esters after esterification (Scheme 1, bottom). 12 This process may proceed directly from the organoBCl 2 or require enhancement of electrophilicity at boron by formation of a borocation. We have previously demonstrated that borocations are effective for the 1,2haloboration and 1,2-carboboration of alkynes, with no 1,1elementoboration observed. 11,13 For example, terminal alkynes and the boronium salt [(Ph)ClB(2-DMAP)][AlCl 4 ] (2-DMAP = 2-N,N-dimethylamino-pyridine) react only by 1,2chloroboration. 11 Based on the previous 1,1-carboboration studies with neutral boranes it was hypothesised that TMSsubstituted alkynes would preferentially undergo 1,1elementoboration over 1,2-elementoboration when combined with organoBCl 2 or borocation compounds. Support for this comes from the work of Curran and co-workers on the 1,1hydroboration of 1-TMS-1-alkynes using borenium equivalents (NHC)BH 2 (NTf) 2 . 14 Herein is reported our studies using arylBCl 2 and aryl and vinyl containing borocations synthesised by electrophilic borylation to effect the carboboration of TMSsubstituted alkynes.

Results and discussion
Vinylboronate ester formation Studies commenced with the boronium cation [Ph(Cl)B(2-DMAP)][AlCl 4 ], 1. 11 The combination of 1 and equimolar 1-TMS-1-propyne at 20 o C resulted in a slow reaction generating a single new silicon containing compound (δ 29Si -6.05) with minimal desilylboration observed (only a low intensity TMSCl resonance present in the 1 H NMR spectra). Heating the reaction to 60 o C in CH 2 Cl 2 in a sealed tube for extended periods (> 1 h) led to complex mixtures, however heating for 30 minutes at 60 o C led to one major new product possessing identical resonances to that observed in the 20 o C reaction, with unreacted 1 also remaining. Esterification of the reaction mixture after 30 minutes with pinacol / Et 3 N led to two major boron containing products, PhBPin (derived from unreacted 1) and a new product isolable by column chromatography. NMR and mass spectroscopy confirmed this to be the product from the 1,1-carboboration of 1-TMS-1-propyne, formed as the Eisomer exclusively, 2a (Table 1). This reactivity was extended to a number of other 1-TMS-1-alkynes to yield 2b to 2e. Using these conditions PhBPin was observed as a minor product from esterification of unreacted 1 in all cases and required separation by column chromatography. The reaction of 1 with TMS-ethyne and trimethyl(3-methylbut-1-yn-1-yl)silane under analogous conditions led to complex intractable mixtures containing significant TMSCl (by 1 H NMR spectroscopy). Si NMR spectroscopy) and a major new 11 B resonance at +6.5 ppm. Esterification enabled identification of the alkynyl pinacol boronate ester confirming desilylboration (equation 1). Desilylboration was observed also on combination of 3 with 1-phenyl-2-TMS-acetylene and with 1-TMS-1-hexyne. Whilst in-situ NMR spectra pre-esterification indicated desilylboration and alkynylborane formation is the dominant reaction outcome, the isolated yields post pinacol esterification were consistently low due to the susceptibility of alkynyl-B species to protodeboronation. 11 In contrast, the combination of 3 and TMS-ethyne only formed the alkynyl-borocation as a minor species (by NMR spectroscopy). The major soluble product contained a vinylic singlet at 6.65 ppm in the 1 H NMR spectrum consistent with alkyne elemento-boration. Crystalline solid spontaneously deposited from CH 2 Cl 2 solutions as the reaction proceeded with a concomitant increase in the quantity of TMSCl and a decrease in the vinylic singlet (by 1 H NMR spectroscopy). The amount of precipitate was increased by using an excess of 3 (5 : 4 ratio of 3 : TMS-ethyne). X-ray diffraction studies on multiple crystals consistently produced poor quality data due to low crystal quality but an unambiguous connectivity map was obtained ( Figure 1, bottom left). This revealed the compound to be the tricationic borate, 4 formed from 1,1-boroamination of TMS-ethyne and desilylboration. Due to the low data quality detailed discussion of structural metrics of 4 is not warranted.  NMR spectrum were observed consistent with four coordinate cationic and anionic boron centres, respectively. The formation of 4 suggested that the CH 2 Cl 2 soluble product formed is 5, the product from 1,1-boroamination of TMS-ethyne prior to intermolecular desilylboration ( Figure 1). Whilst 5 could not be isolated analytically pure (due to contamination with 4, the alkynyl-borocation and [H(2-DMAP)][AlCl 4 ]) multinuclear NMR spectroscopy is fully consistent with this formulation with NOE spectroscopy confirming the regio-and stereo-chemistry and indicating that the desilylboration of 5 to form 4 occurs with retention. The reactivity disparity between TMS-ethyne and other 1-TMS-1-alkynes studied is attributed to a less stabilised vinyl cation formed on interaction of 3 with TMS-ethyne which presumably favours rapid TMS-migration leading to 5 as the initial product and not the alkynyl-borocation from desilylboration. It is noteworthy that the reaction of [Cl 2 B(2,6lutidine)][AlCl 4 ], 6, a borocation where the amine does not contain a pendant nucleophile, with 1-TMS-alkynes, including TMS-ethyne, led predominantly to desilylboration in all cases. Whilst the reactivity of 1-TMS-1-alkynes with BCl 3 proceeds by desilylboration 15 the analogous reactivity with PhBCl 2 has not been explored to the best of our knowledge. To determine if PhBCl 2 and 1 react comparably with 1-TMS-1-alkynes equimolar 1-TMS-1-propyne and PhBCl 2 were combined in CH 2 Cl 2 at 20 o C. This resulted in a rapid reaction producing a single new product identified by multinuclear NMR spectroscopy as the product from 1,1-carboboration. Post esterification 2a was isolated in a higher yield than when using 1. A substrate scope exploration (table 2) confirmed that the 1,1-carboboration of 1-TMS-1-alkynes with PhBCl 2 consistently proceeds in higher yield than when using 1 and does not require purification by chromatography post esterification. Furthermore, the structure of 2e was also confirmed by a single crystal X-ray diffraction study ( Table 2, right). It is noteworthy that trimethyl(4-phenylbut-1-yn-1-yl)silane (entry 7) resulted in only 1,1-carboboration with no 6-endo-dig cyclisation as recently reported for related alkynes and BCl 3 . 16 The facile formation of 2a -2h by 1,1-carboboration represents an alternative to transition metal catalysed borosilyation of alkynes for accessing these versatile intermediates. 17 Attempts to extend this reaction to 1triisopropylsilyl-1-propyne resulted in no reaction, whilst combining PhBCl 2 and 1-(PhMe 2 Si)-1-propyne resulted predominantly in desilylboration products (by observation of PhMe 2 SiCl by 1 H and 29 Si NMR spectroscopy) and multiple other currently unidentified products.
To increase the scope, variation of the aryl substituent on the borane was explored. ArylBCl 2 and heteroarylBCl 2 species are readily accessible by electrophilic arene borylation. 10 Using established methodologies 2-methylthiophene, 2-methylfuran, chlorobenzene and triphenylamine were all borylated to produce the respective (hetero)arylBCl 2 compounds 7a -7d (table 2) in good conversion as determined by multi-nuclear NMR spectroscopy. 10a, b Removal of reaction solvent (CH 2 Cl 2 or 1,2-Cl 2 C 6 H 4 ) and extraction of 7a -d into hexanes was sufficient to enable subsequent reaction with 1-TMS-1propyne without any additional purification steps. This led to the formation of the desired 1,1-carboboration products which were esterified to form a single regio-and stereo-isomer of the respective vinyl pinacol boronate esters (entries 9 -12). The products derived from carboboration using 7a and 7b were repeatedly contaminated with minor quantities of heteroarylBPin (from esterfication of unreacted 7a and 7b) which in our hands proved challenging to separate from 2i and 2j. The 1,1-carboboration reaction using longer times (3 h) for 7a and 1-TMS-1-propyne led to considerably more complex NMR spectra and intractable products post esterification. Attempts to extend 1,1-carboboration using 7a -7d to other 1-TMS-1-alkynes, specifically 1-TMS-2-phenylacetylene and trimethyl(3-methylbut-1-yn-1-yl)silane, instead led to desilylboration being the dominant reaction pathway (by 1 H, 11 B and 29 Si NMR spectroscopy). To preclude the disparity between PhBCl 2 and the four (hetero)arylBCl 2 compounds 7ad being due to any impurities in commercially sourced PhBCl 2 or impurities in (hetero)arylBCl 2 synthesised by electrophilic borylation, benzene was borylated in 1,2-Cl 4 C 6 H 4 using 4,N,Ntrimethylaniline, BCl 3 and two equivalents of AlCl 3 to form PhBCl 2 .
10c This reaction mixture was dried and PhBCl 2 extracted into hexane and found to form 2f on addition of trimethyl(3-methylbut-1-yn-1-yl)silane, a substrate that 7a -d react with predominantly by desilylboration. Therefore the greater prevalence for desilylboration using 7a-d is attributed to the modified electrophilicity of the borane and the different migratory propensity of the (hetero)aryl group (relative to phenyl), indicating that the 1,1-carboboration of 1-TMS-1alkynes using (hetero)arylBCl 2 compounds is limited in scope. PhBCl 2 was effective for the carboboration of silylated allenes with 8a and 8b (Scheme 2) undergoing carboboration with TMS migration producing only a single allylBCl 2 product (by multinuclear NMR spectroscopy). With no intermediates observed we attribute the reaction outcome to a 1,1carboboration followed by a rapid intramolecular sigmatropic 1,3-boron shift to form the more thermodynamically stable less hindered allylBCl 2 species. 18 This can be subsequently pinacol protected and the resultant boronate esters 9a and 9b isolated. This enables access to complementary boronate ester isomers to that produced by the hydroboration of closely related TMS-allenes where TMS migration does not occur. 19 Scheme 2: The carboboration of TMS-allenes with PhBCl2.

Boradiene formation using borocations
To explore potential scope expansion further [5-methyl-2-(BCl(2-DMAP))-thiophene][AlCl 4 ], 10, was synthesised by addition of 2-DMAP and AlCl 3 to 7a. The addition of 1-TMS-1propyne to 10 resulted in a slow reaction at 20 o C that after 18 hours produced four new TMS resonances one of which was attributable to the 1,1-carboboration product (by 1 H, 11 B and 29 Si NMR spectroscopy). One of the other new compounds derived from 10 / 7a could be formed as a greater component of the reaction mixture when an excess of 1-TMS-1-propyne (5 equivalents) was used with heating to 60 o C for 18 h. Post esterification, isolation by column chromatography and analysis by NMR and mass spectroscopy enabled it to be identified as the 2-boradiene 11a, from reaction of 10 with two equivalents of 1-TMS-1-propyne. Under identical conditions 1 also reacted with excess 1-TMS-1-propyne to produce the 2-boradiene 11b as a minor product. In contrast, heating PhBCl 2 with excess (5 equiv.) 1-TMS-1-propyne led to no observable 2-boradiene after esterification with pinacol, instead complex mixtures were produced with significant TMSCl observed in-situ indicating desilylboration. Under a range of conditions 11a and 11b were formed only as minor products from 10 and 1 (with a maximum 13 and 15% isolated yield, respectively) with the 1,1-carboboration products, 2i and 2a, being the major species isolated post esterification. 2-Boradienes related to 11x have been previously synthesised by Wrackmeyer and co-workers from the reaction of BEt 3 with two equivalents of 1-R 3 Sn-1-alkynes. 20 Precise isomer assignment for 11x was based on 1D and 2D NMR spectroscopy, most notably NOESY indicated a trans- disposition of TMS and PinB moieties in the 2-boradiene. This is in contrast to that in 2x suggesting that 1,1-carboboration is not the first step in 2-boradiene formation, a hypothesis supported by the fact that resonances for the 1,1carboboration products increase in intensity as the reaction progresses, suggesting it is not an intermediate in diene formation. Instead we propose that 1-TMS-1-propyne is activated to an intermolecular attack by a second equivalent of alkyne by interaction with the borocation and this ultimately leads to the observed 2-boradiene structures. Related borane activation of alkynes towards external π nucleophiles have been reported previously. 2b, 21 As repeated attempts to crystallise 11a and 11b failed in our hands to support the proposed diene structure, particularly correlating the structure with the multiple NOE interactions observed, the structure of 11b was optimised at the M06-2X/6-311G(d,p)(PCM:DCM) level. This revealed that steric bulk forces a significant dihedral angle in the diene (C=C-C=C = 60.24 o ) and thus short distances (< 4 Å) were observed in the calculated structure for all the observed NOE interactions, supporting this isomer assignment. Attempts to form other 2-boradienes using different (hetero)arylboronium cations or different TMS-alkynes all led to complex mixtures and lower conversions than that observed for 11a and 11b.
Subsequently, the one pot, two step reaction of 3 with terminal alkynes (proceeding by 1,2-haloboration as previously reported to form 12x, equation 2) 11 followed by addition of 1-TMS-1-propyne was explored as an alternative route to 2boradienes. The addition of 1-TMS-1-propyne to 12a or 12b gave no reaction (by NMR spectroscopy) at room temperature after 18 hours. When the reaction mixture was heated to 60°C for 1 h multiple new species were observed in the 1  Please do not adjust margins Please do not adjust margins resonances at +55 and +66 ppm. Esterification and attempts to purify the resultant complex mixture failed to deliver pure products in our hands. A more electrophilic vinyl-borocation was targeted to enable room temperature reactivity with 1-TMS-1-alkynes and potentially avoid the complex mixtures observed with 12x at 60 o C. Thus the reactivity of [(vinyl)BCl(2,6-lutidine)] + cations, made via haloboration of alkynes with 6, with 1-TMS-1-alkynes was explored. In a one pot two step reaction 6 was used to separately haloborate t Bu-acetylene and phenylacetylene followed by addition of one equivalent 1-TMS-1-propyne, which did not lead to any significant TMSCl formation at short reactions times (< 1 h by NMR spectroscopy) in each case. The initial haloboration step is rapid (complete in < 5 minutes with both terminal alkynes) whilst the subsequent reaction with 1-TMS-1-propyne is slower it did proceed to form carboboration products (Scheme 4). Running the reaction for longer times at 20 o C (≥ 2 h) resulted in significant TMSCl formation, whilst attempts to use greater equivalents of 1-TMS-1-propyne also led to more TMSCl formation; thus optimized conditions of 1.2 equivalents of 1-TMS-1-propyne and a 1 h reaction duration were found to minimise the amount of unreacted haloboration compounds (12a-b) remaining and TMSCl formation. Post esterification the boradiene products 13a-b could be separated from the vinyl-pinacol boronate esters (formed from esterification of unreacted 12a-b) with NMR spectroscopy consistent with a 1-boradiene formulation formed from a 1,2carboboration reaction (Scheme 4). Notably a 4 J HH coupling of 1 Hz is observed between the methyl and the vinyl-H in both 13a and 13b confirming the connectivity as this coupling would not be observed in the 1,1-carboboration products. Whilst  , thus the barrier to the reverse process (retrovinylboration) will be significantly higher than that for the forward reaction (which requires at least 1 h for significant conversion).
As bora-dienes are useful species for a range of subsequent synthetic transformations, 24 the broader applicability of this reaction was explored initially looking at other terminal alkynes. 12c -12e were all readily produced by haloboration with 6 and underwent 1,2-carboboration to form 13c -13e, however the isolated yields of 13x are poor to moderate (23 -59 %), whilst 13d and 13e could not be separated from reaction by-products. The propensity of other 1-TMS-1-alkynes to undergo 1,2-carboboration, specifically 1-TMS-2phenylacetylene and 1-TMS-1-hexyne, were investigated using 12a, however the reaction was slower (by in-situ NMR spectroscopy) and resulted in lower conversions to the desired boradiene and more unidentified by-products. Finally, the use of an internal alkyne, 3-hexyne, was investigated, which as previously reported underwent facile haloboration with 6, 11 but subsequent reaction with 1-TMS-1-propyne resulted in a low conversion to the 1-boradiene product which was isolated as the pinacol boronate ester, 13f in only 10% yield. The low conversions with more substituted systems is presumably due to the increased steric crowding resulting in the slower formation of the 1,2-carboboration products and thus increased formation of by-products derived from desilylboration.

Conclusions
The carboboration of 1-TMS-1-alkynes with aryldichloroboranes and aryl-substituted and vinyl-substituted borocations has been demonstrated to yield highly substituted vinyl and dienyl boronate esters post esterification. However, due to carboboration occurring in competition with desilylboration and diene formation, coupled with further reactions proceeding subsequent to the initial carboboration (e.g., further desilylboration), complex mixtures are often produced that limit the overall utility of this reaction. Variation Please do not adjust margins Please do not adjust margins in borane and borocation structure is therefore essential to preclude desilylboration to generate more general and higher yielding 1-TMS-1-alkyne carboboration protocols.

Experimental
General Considerations: all manipulations of air and moisture sensitive species were performed under an atmosphere of argon or nitrogen using standard Schlenk and glovebox techniques. Glassware was dried in a hot oven overnight and heated before use. Hexane, ortho -dichlorobenzene, d 1chloroform, d 2 -dichloromethane, 2,6-lutidine, Et 3 N and were dried over calcium hydride and distilled under vacuum. Pentane and dichloromethane were dried by passing through an alumina drying column incorporated into an MBraun SPS800 solvent purification system. All solvents were degassed and stored over molecular sieves ( ] (50 mg, 0.12 mmol, 1 eq) in DCM (0.5 ml) in a J. Youngs NMR tube was added 1-TMS-1-alkyne (0.12 mmol, 1 eq). This was sealed and the mixture heated for 30 minutes after which time an excess of triethylamine (0.1 ml) and pinacol (30 mg, 0.24 mmol, 2 eq) were added and the solvent was removed under reduced pressure to leave an oil. Pentane was used to extract the product, which was passed through a 1 inch plug of silica to remove pinacol impurities. Column chromatography (DCM:hexane, 1:1) was used to separate the desired product from the by-products.
With PhBCl 2 (Route 2) To a solution of PhBCl 2 (200 μl, 1.5 mmol, 1 eq) in DCM (5 ml) in a Schlenk was added 1-TMS-1-alkyne (1.5 mmol, 1 eq). After x hours an excess of triethylamine (0.5 ml) and pinacol (350 mg, 3.0 mmol, 2 eq) were added, and the solvent was removed under reduced pressure to leave an oil. Filtration through a 1 inch plug of silica afforded the product in good purity without column chromatography.
After 30 minutes the reaction mixture was esterified with excess Et 3 N (0.1 ml) and pinacol (78 mg, 3 eq). The crude product was extracted into pentane (20 ml) and filtered through a 1 inch plug of silica afforded the product. (74 mg, 68% Si NMR (79.5 MHz, CH 2 Cl 2 ) δ -3.6 ppm. Due to difficulties in purifying this compound, the 13 C NMR spectra were complicated by numerous minor species. Accurate elemental analysis could not be obtained due to the impure nature of the material from each attempt to isolate this product.