Stereocontrolled Synthesis of Highly Functionalized Quaternary Carbon Centers: A Route to α‐Substituted Serines

Abstract

Three in a row! Highly functionalized quaternary amino polyols with three consecutive asymmetric carbon centers have been prepared through tandem hydroboration of allene 1 and addition to an aldehyde (see scheme; Cy = cyclohexyl, TBDPS = tert-butyldiphenylsilyl, Ts = 4-toluenesulfonyl). This one-pot process provides access to advanced intermediates for the enantioselective synthesis of alpha-substituted serines.

Synthesis of Polyketide Stereoarrays Enabled by a Traceless Oxonia‐Cope Rearrangement

“…[9] With this notion in mind, we began to evaluate the feasibility of the oxonia-Cope rearrangement of racemic syn,syn-2 a (Table 1), [10] which was readily prepared from the hydroboration of the TBS-protected a-allenic alcohol 1 a with 9-BBN and subsequent allylation of propanal. [11] In contrast to literature precedents using Brønsted acids, such as p-TsOH, CSA, and TfOH, [7] several undesired reactions including desilylation and ketalization, Prins cyclization, and cation-initiated rearrangements were found to occur with syn,syn-2 a. A variety of Lewis acids were thus executed.…”

2-Vinyl Threoninol Derivatives via Acid-Catalyzed Allylic Substitution of Bisimidates

“…Choice of the solvent had a significant effect on the product 2a/9 ratio. The seven-membered imidate 9 was formed in considerable amounts when lower polarity solvents such as DCM or Et 2 O were used (Table 1, entries [3][4][5][6]. Notably, compound 9 was formed as the major product with Fe(OTf) 3 as a catalyst in toluene (Table 1, entry 7).…”

Stereoselective preparation of quaternary 2-vinyl sphingosines and ceramides and their effect on basal sphingolipid metabolism

“…We recently reported a highly stereoselective addition of N-tosyl allene 3 to aldehydes leading to protected tosylcarbamates (±)-4. 5 This one-pot process is based on the hydroboration of the allene with (c-C 6 H 11 ) 2 BH at the less hindered face of the terminal double bond to generate an allylborane which could be added in situ to an aldehyde (Scheme 1). However, in practice, the use of tosyl as N-protecting group suffers from some drawbacks.…”

“…4 Based on the above precedents, it is conceivable that the introduction of the 2-amino-2-vinyl-1,3-diol core as part of the sphingolipid framework represents an attractive modification for the design of new modulators of sphingolipid metabolism. In this work, we present an adaptation of our previously reported protocol 5 to the enantioselective synthesis of quaternary 2-vinyl sphingosines 9 (Figure 1). In addition, studies on their cellular metabolism, cellular toxicity and effects on basal sphingolipid metabolism in human A549 lung adenocarcinoma cells are discussed.…”