The general structure of a stannatrane reagent, where variants have been synthesized with X=C (carbastannatrane) and X=N (azastannatrane) and R is an alkyl or aryl substituent.
A stannatrane (IUPAC: 1-aza-5-stannabicyclo[3.3.3]undecane) is a
tin-based
atrane belonging to the larger class of
organostannanes. Though the term stannatrane is often used to refer to the more commonly employed carbastannatrane, azastannatranes have also been synthesized (prefix refers to the identity of the
atom bound directly to tin center).[1] Stannatrane reagents offer highly selective methods for the incorporation of "R"
substituents in complex molecules for late-stage diversification. These reagents differ from their tetraalkyl organostannane analogues in that there is no participation of
dummy ligands in the
transmetalation step, offering selective
alkyl transfer in
Stille Coupling reactions.[2][3][4] These transmetalating agents are known to be air- and moisture-stable, as well as generally less toxic than their tetraalkyl counterparts.
History and structural properties
The first carbastannatrane was reported in 1984 by Jurkschat and Tzschach.[5] By reaction of an amino-tri
Grignard reagent with
tin(IV) chloride to yield the stannatrane chloride, which was treated with
methyl lithium to yield the corresponding methyl stannatrane. Based on a very small methyl J(119Sn–13C)
coupling constant of 171 Hz, it was determined that the tin center of methyl stannatrane was indeed
pentacoordinate, indicating nitrogen coordination.
Synthesis of stannatrane chloride and methyl stannatrane by Jurkschat and colleagues.Stereoscopic representation of methyl stannatrane crystal structure.
The crystal and molecular structure was explained by
X-ray crystallography.[6] The X-ray diffraction study confirmed the tricyclic ring structure and gave insight toward the geometry of the complex. With a tin-nitrogen distance of 2.624 Å, the formal
bond order was calculated to be about 0.46. The presence of the tin-nitrogen interaction, albeit weaker than anticipated, led to a few key discoveries: (1) the distortion from ideal
trigonal bipyramidal toward
monocapped tetrahedron geometry;[7] (2) the lengthening of the apical tin-methyl bond by ~ 0.1 Å (largest known value for any existing tetraorganotin compounds); (3) the observation of unusual
hybridization at the apical tin-methyl bond.
(1) Hydrozirconation method for synthesizing stannatrane chloride. (2) Synthesis of lithium carbastannatrane and subsequent mesylate displacement.
Though the latter step is still commonly used for functionalization of stannatrane chloride to simple alkyl derivatives viatransmetalation, Biscoe and coworkers have developed a lithiation method that provides access to a variety of enantioenriched alkyl substituents from optically active mesylates (2).[9][10] After treatment of stannatrane chloride with lithium napthalide, a lithium carbastannatrane was quenched with the corresponding enantiopure mesylate to yield the desired enantioenriched alkyl carbastannatrane in moderate yield with high
enantiomeric excess.
Applications in cross-coupling
The earliest reported use of carbastannatranes in palladium-catalyzed Stille coupling reactions in 1992 compared the efficiency of methyl stannatrane with
tetramethyltin in the presence of aryl bromides and alkenyl iodides.[8] Tetramethyltin only resulted in less than five percent conversion, whereas methyl stannatrane resulted in 67% yield under the same conditions. This difference was attributed to the nitrogen
lone pair lengthening the tin-methyl bond, increasing its lability toward
transmetalation. A method was developed for Stille couplings of aziridinyl stannatranes with aryl
electrophiles.[11]
A stereoretentive Stille coupling using alkyl carbastannatranes.
Palladium also catalyzes Stille coupling of secondary alkyl carbastannatranes and aryl electrophiles.[12][13] This report serves as the first example of employing
chiral alkyl carbastannatrane reagents in
enantioselective synthesis. Related methodology enable selective acyl substitution using enantioenriched stannatranes as an alternative to classical
enolate chemistry.[9]
A stannatrane-mediated Stille coupling was utilized for the synthesis of an anti-
methicillin-resistantcarbapenem to incorporate an entire side-chain in a single step.[14]
References
^Plass, Winfried; Verkade, John G. (1993-11-01). "Azastannatranes: synthesis and structural characterization". Inorganic Chemistry. 32 (23): 5145–5152.
doi:
10.1021/ic00075a034.
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^Stille, John K. (1986-06-01). "The Palladium-Catalyzed Cross-Coupling Reactions of Organotin Reagents with Organic Electrophiles [New Synthetic Methods (58)]". Angewandte Chemie International Edition in English. 25 (6): 508–524.
doi:
10.1002/anie.198605081.
ISSN1521-3773.
^Hartwig, John Frederick (2010-01-01). Organotransition metal chemistry : from bonding to catalysis. University Science Books.
ISBN9781891389535.
OCLC781082054.
^Jurkschat, K.; Tzschach, A. (1984). "1-Aza-5-stanna-5,5-dimethylbicyclo[3.3.01,5] octan und 1-aza-5-stanna-5-methyltricyclo[3.3.3.01,5] undecan, pentakoordinierte tetraorganozinnverbindungen". Journal of Organometallic Chemistry. 272: C13–C16.
doi:
10.1016/0022-328X(84)80450-7.
^Jurkschat, K.; Tszchach, A.; Meunier-Piret, J. (1986). "Crystal and molecular structure of 1-AZA-5-STANNA-5-methyltricyclo[3.3.3.01,5]undecane. Evidence for a transannular donor−acceptor interaction in a tetraorganotin compound". Journal of Organometallic Chemistry. 315: 45–49.
doi:
10.1016/0022-328X(86)80409-0.
^Crabtree, Robert H. (2014-04-21). The organometallic chemistry of the transition metals. Wiley.
ISBN9781118138076.
OCLC930855497.
^
abVedejs, Edwin; Haight, Anthony R.; Moss, William O. (1992). "Internal coordination at tin promotes selective alkyl transfer in the Stille coupling reaction". Journal of the American Chemical Society. 114 (16): 6556–6558.
doi:
10.1021/ja00042a044.
^Wang, Dong-Yu; Wang, Chao; Uchiyama, Masanobu (2015-08-26). "Stannyl-Lithium: A Facile and Efficient Synthesis Facilitating Further Applications". Journal of the American Chemical Society. 137 (33): 10488–10491.
doi:
10.1021/jacs.5b06587.
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^Theddu, Naresh; Vedejs, Edwin (2013). "Stille Coupling of an Aziridinyl Stannatrane". The Journal of Organic Chemistry. 78 (10): 5061–5066.
doi:
10.1021/jo4005052.
PMID23581391.
^Jensen, Mark S.; Yang, Chunhua; Hsiao, Yi; Rivera, Nelo; Wells, Kenneth M.; Chung, John Y. L.; Yasuda, Nobuyoshi; Hughes, David L.; Reider, Paul J. (2000-04-01). "Synthesis of an Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Carbapenem via Stannatrane-Mediated Stille Coupling". Organic Letters. 2 (8): 1081–1084.
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10.1021/ol005641d.
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