Asymmetric Synthesis of Isomerically Pure Allenyl Boranes from Alkynyl Boranes through a 1,2‐Insertion–1,3‐Borotropic Rearrangement

Abstract

Very recently, we described a variety of new 10-trimethylsilyl-9-borabicyclo[3.3.2]decane (10-TMS-9-BBD) reagents for the asymmetric allyl-, crotyl-, allenyl-, and propargylboration of aldehydes.[1] Prepared through adaptations of known organoborane transformations, these rigid and robust trialkyl borane systems are exceptionally stable and selective. Moreover, the related 10-Ph-9-BBD reagents, which are quite effective for the related addition reactions to ketones and ketimines, can also be prepared readily. [2] Simple Grignard procedures can be used to prepare many of these reagents, including the B-alkynyl 10-TMS-9-BBDs (2), the asymmetric Michael addition of which to N-acyl aldimines provides nonracemic N-propargyl amides.[3] On the basis of modeling studies with 2, we envisaged the highly stereoselective insertion of TMSCHN 2 into the alkynyl BÀC bond of 2 to give 4 via 3 (Scheme 1). An antiperiplanar 1,2-alkynyl migration (Matteson-type homologation) [4a] followed by a sterically driven suprafacial 1,3-borotropic rearrangement were expected to proceed with a minimum of TMS-TMS repulsions and ultimately convert the propargyl borane 4 into the novel chiral allenyl borane 1. [1c, 2a, 4b] The thermally stable, optically pure alkynyl boranes 2 (a: R = Me; b: R = (CH 2 ) 4 Cl; c: R = c-Pr; c-Pr = cyclopropyl) are readily prepared in either enantiomeric form through the reaction of the corresponding alkynyl Grignard reagents with the pseudoephedrine complexes 6 (96-99 %). At room temperature, TMSCHN 2 reacts cleanly with 2 with the evolution of nitrogen to form 1 ( 11 B NMR: d = 78 ppm) in 3 h. We view this process as occurring through the reversible addition of TMSCHN 2 to the least hindered side of 2, followed by the insertion of CHTMS into 2 with inversion. The chiral a-borylallenes 1 are then produced in enantiomerically and diastereomerically pure form in essentially quantitative yield by a suprafacial 1,3-borotropic rearrangement (Scheme 1).Asymmetric allenylboration [1b, 2c, 5] is a highly useful organoborane transformation. Compound 1 was tested as an asymmetric allenylboration reagent with representative aldehydes (Scheme 2). The addition was rapid at À78 8C (3 h), and the intermediate borinic esters 5 produced were either oxidized or converted into the pseudoephedrine complexes 6 for recycling back to 2 by the Grignard methodology. The syn b-TMS homopropargylic alcohols 7 were isolated in 80-96 % yield with d.r. 99:1 and 94-99 % ee (Table 1). This process is more enantioselective than allenylboration with the parent B-allenyl system (93-95 % ee).[1b] The enhanced enantioselectivity can be attributed to the additional a substituent Scheme 1. The preparation of 1 from 2 through insertion-borotropic rearrangement. TMS = trimethylsilyl.Scheme 2. Asymmetric allenylboration with 1.

Concise Total Synthesis of Cruentaren A

“…[18] Temporary protection of the free hydoxy group in 22 paved the way to the nonterminal alkyne 25 as the other required component for the envisaged alkyne metathesis reaction. [19] In contrast to the straightforward preparation of the major building blocks, the seemingly trivial esterification of 14 and 25 posed considerable problems. All attempts to join them by using carbodiimide-based reagents, the standard activating agents commonly employed in peptide synthesis, by means of activated esters and thioesters, or by the Yamaguchi method [20] either led to complete failure or resulted in the decomposition of the valuable materials.…”

Preparation, Modification, and Evaluation of Cruentaren A and Analogues

“…[36] Temporary protection of the free OH group as TES ether 23 paved the way to the nonterminal alkyne 25 as the other required component for the envisaged alkyne metathesis reaction. [38] The final selective cleavage of the TES group was accomplished with HF·pyridine in pyridine/THF as the reaction medium. It was noticed that the use of Teflon flasks rather than the usual glassware was highly beneficial, as fewer equivalents of HF and shorter reaction times sufficed to reach complete conversion.…”

Allenes in Catalytic Asymmetric Synthesis and Natural Product Syntheses

“…These reagents could also be transformed into the corresponding optically pure allenylsilanes through simple protonolysis (Scheme 15). [47][48][49] The hydroboration of 1,2-butadien-3-yl boronate 58 with ( d Ipc) 2 BH followed by allylboration of an aldehyde and oxidative workup gave the 1,2-syn-or 1,2-anti-diol diastereomers 59 or 60; which diastereomer was obtained could be controlled by the hydroboration conditions (Scheme 16). [50,51] In Fürstners approach to the antibiotic macrolide myxovirescin A1, one of the segments was prepared from chiral aldehyde 62 by means of Browns anti-selective allylboration.…”