Stereoretentive Addition of N‐tert‐Butylsulfonyl‐α‐Amido Silanes to Aldehydes, Ketones, α,β‐Unsaturated Esters, and Imines

Abstract

Abstract:Enantioenriched N-tert-butylsulfonyl--amido silanes were successfully reacted with aldehydes, ketones, imines, and ,-unsaturated esters in the presence of a sub-stoichiometric amount of CsF (0.5 equiv) in DME at -20 o C to afford the corresponding coupling products with up to 89% enantiospecificity in a retentive manner.The construction of C-C bonds with preservation of the optical purity of nucleophiles is a formidable challenge in organic synthesis. [1] Although transition-metal-catalyzed stereospecific cross-coupling reactions have been actively studied in this field, [2] much attention is still being paid to non-catalytic processes using highly reactive nucleophiles. [3][4][5][6] Among the latter examples, stereospecific additions of secondary and tertiary alkyllithium species have been extensively studied over the past three decades. [3] For instance, enantioenriched organolithium species, which are prepared by tin-lithium exchange from the corresponding optically active organostannanes and n-or s-BuLi, [4] deprotonation of enantioenriched carbamate-protected derivatives with BuLi and TMEDA, [5] or asymmetric deprotonation of achiral substrates using BuLi and (-)-sparteine as a chiral ligand, [6] reacted with a range of electrophiles in a stereoretentive/invertive manner. However, a very low temperature (below -78 o C) was often required in order to maintain their optical purities as much as possible. Moreover, the use of highly nucleophilic BuLi attenuates the synthetic utility due to the low functional group tolerability and the need for strictly anhydrous conditions. On the other hand, less reactive alkylboron [7] and silane [8] reagents were also employed for the stereospecific addition in combination with an appropriate activator. Although -addition of enantioenriched allylborons/silanes has already been established, [7a-d,8a-c] stereospecific transformation of C(sp 3 )-B/Si into C(sp 3 )-C bonds is still challenging, and this has motivated us to develop a new method with a high level of enantiospecificity for versatile electrophiles under mild conditions.Our research group already reported a stereoretentive carboxylation of -amino silanes 1 with CO 2 in the presence of CsF in DMF solvent at -20 o C, affording the corresponding -amino acids with up to 86% enantiospecificity (Figure 1). [9,10] The starting enantioenriched N-tert-butylsulfonyl--amido silanes 1 can be synthesized either from Ellman's chiral sulfinyl imines by diastereoselective silylation [11] followed by oxidation or from sulfonyl imines by Cu(I)-catalyzed enantioselective silylation recently developed by our group. [10] In contrast, the use of NBoc--amido silanes 1b under the same conditions gave racemic compounds, [12] suggesting that the Boc substitution enhances carbanion generation, whereas the sulfonyl group might stabilize a fluorosilicate intermediate in the stereoretentive transformation. We herein disclose the detection of a fluorosilicate species using 19 F-29 Si 2D NMR spectroscopy in addition to other p...

Syntheses of α‐Amino Acids by Using CO2 as a C1 Source

“…Af luorosilicate, an intermediate to maintain high stereospecificities,w as observedb y 29 Si-19 F2 DNMR analysis. [17] The tert-butylsulfonyl group wasr eadily cleaved in the presence of AlCl 3 and anisole withoutthe loss of enantioselectivity.…”

“…The subsequent CsF‐mediated carboxylation reaction proceeded in a stereoretentive manner to afford the corresponding α‐amino acids with high enantiospecificities (up to 86 % es). A fluorosilicate, an intermediate to maintain high stereospecificities, was observed by 29 Si– 19 F 2D NMR analysis . The tert ‐butylsulfonyl group was readily cleaved in the presence of AlCl 3 and anisole without the loss of enantioselectivity.…”

“…In this transformation, ammonium ylide intermediates could react with CO 2 .T herefore, neither a-aryl nor alkenyl substituents were necessary for the generation of an a-carbanion prior to carboxylation with CO 2 ,w hichr epresented as ignificant advantage over existing methods by using a-amino metalloid species. [11][12][13][14][15][16][17][18]…”

Copper-Catalyzed Enantioselective Reductive Cross-Coupling of Aldehydes and Imines

“…Many synthetic methods for chiral β-amino alcohols have been reported so far. , One of the most direct and facile methods is the enantioselective reductive cross-coupling using carbonyls and imines due to the high availability of these substrates in organic synthesis. However, this method is limited to only a few cases . Specifically, Lin, Xu, and co-workers demonstrated the enantioselective cross-pinacol type coupling of aldehydes and Ellman’s chiral sulfinyl imines (Figure A-a) .…”

“…This protocol was also applicable to ketimine 2m , allowing the construction of chiral β-amino alcohols 3am – 3 cm and 3gm bearing a highly congested carbon scaffold. These β-amino alcohols are difficult to prepare with the reductive cross-coupling system reported by Lin and Sato …”